RESUMO
AIM: To compare targeted and global liver stiffness measured by magnetic resonance elastography (MRE) with liver biopsy in patients who have undergone the Fontan procedure, and to assess the relationship between liver stiffness and fibrosis stage. MATERIALS AND METHODS: Targeted and global liver stiffness was compared with a quantification of liver fibrosis measured by percentage of Sirius Red (%SR) staining of biopsy samples. MRE values were compared with three other biopsy-scoring methods: Ishak, Scheuer/Ludwig-Batts/Metavir, and congestive hepatic fibrosis score (CHFS). Additionally, in patients who had two or more MRE studies, global liver stiffness was compared for longitudinal assessment. RESULTS: Thirty-four patients were included in the study, with a mean age of 16.2 years. There was no statistically significant correlation between MRE-derived liver stiffness and Ishak score, Metavir score, %SR staining, and CHFS score. Twenty patients had multiple MRE studies, with a mean age of 16.5 years, and these showed a statistically significant increase in mean liver stiffness from 3.72 to 4.68 (26% increase) within an average period of 24 months. CONCLUSIONS: The lack of correlation of liver stiffness with fibrosis stage observed in this study indicates that the effects of venous congestion in Fontan patients can confound the use of liver stiffness as a biomarker for fibrosis as assessed by percentage of SR staining, Ishak score, Metavir score, and CHFS score. These results provide motivation for further development of magnetic resonance imaging-based biomarkers to increase the specificity in the assessment of Fontan-associated liver disease. A steady increase in liver stiffness observed in these patients may be useful for longitudinal follow-up of liver health.
Assuntos
Técnicas de Imagem por Elasticidade , Técnica de Fontan , Hiperemia , Hepatopatias , Adolescente , Técnicas de Imagem por Elasticidade/métodos , Fibrose , Técnica de Fontan/efeitos adversos , Humanos , Hiperemia/diagnóstico por imagem , Hiperemia/etiologia , Hiperemia/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatias/etiologia , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
One of the most frequent causes of cardiac embolism in cryptogenic stroke is a paradoxical embolus, which originate from systemic venous source though an unidentified patent foramen ovale (PFO). PFO is a common finding in the general population with a prevalence of 25% to 30%. Transcatheter PFO device closure is known to be feasible and safety treatment for such patients. In recent years, several randomized controlled trials (RCTs) have been conducted to address the superiority of PFO closure over medical therapy alone in the prevention of stroke recurrence in patients with PFO. In contrast to findings from early 3 RCTs, recent 4 RCTs could successfully show the benefits of PFO device closure compared with medical therapy, with less peri- and postprocedural complication. Based on these data, PFO device closure is recommended to carefully select cryptogenic stroke patients aged from 18 to 65 years, with a high probability of a causal role of the PFO in stroke events. However, it is still uncertain whether PFO closure is superior to oral anticoagulants therapy in these patients. Therefore, further prospective randomized trials are needed to address the efficacy of PFO device closure to oral anticoagulants therapy.
Assuntos
Cateterismo Cardíaco/instrumentação , Forame Oval Patente/complicações , Forame Oval Patente/cirurgia , AVC Isquêmico/etiologia , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/economia , Análise Custo-Benefício , Forame Oval Patente/tratamento farmacológico , Humanos , AVC Isquêmico/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias , Prevenção SecundáriaRESUMO
Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.
Assuntos
Janus Quinase 2/genética , Mutação/genética , Transtornos Mieloproliferativos/genética , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Análise Citogenética , Europa (Continente) , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/terapia , Recidiva Local de Neoplasia/genética , Neoplasia Residual/genética , Prognóstico , RNA Mensageiro/genética , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante de Células-Tronco , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: There is no prognostic index for primary cutaneous T-cell lymphomas such as mycosis fungoides (MF) and Sezary syndrome (SS). METHOD: Two prognostic indices were developed for early (IA-IIA) and late stage (IIB-IVB) disease based on multivariate data from 1502 patients. End-points included overall survival (OS) and progression free survival (PFS). External validation included 1221 patients. FINDINGS: Significant adverse prognostic factors at diagnosis consisted of male gender, age >60, plaques, folliculotropic disease and stage N1/Nx for early stage, and male gender, age >60, stages B1/B2, N2/3 and visceral involvement for late stage disease. Using these variables we constructed two separate models each defined using 3 distinct groups for early and late stage patients: 0-1 (low risk), 2 (intermediate risk), and 3-5 factors (high risk). 10 year OS in the early stage model was 90.3% (low), 76.2% (intermediate) and 48.9% (high) and for the late stage model 53.2% (low), 19.8% (intermediate) and 15.0% (high). For the validation set significant differences in OS and PFS in early stage patients (both p<0.001) were also noted. In late stage patients, only OS differed between the groups (p=0.002). INTERPRETATION: This proposed cutaneous lymphoma prognostic index provides a model for prediction of OS in early and late stage MF/SS enabling rational therapeutic choices and patient stratification in clinical trials.
Assuntos
Micose Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Neoplasias Cutâneas/diagnóstico , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Micose Fungoide/sangue , Micose Fungoide/mortalidade , Micose Fungoide/patologia , Micose Fungoide/terapia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco , Síndrome de Sézary/sangue , Síndrome de Sézary/mortalidade , Síndrome de Sézary/patologia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Fatores de TempoRESUMO
OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib. ALK copy-number abnormalities have also been described. In this study, we evaluated the suitability of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in endobronchial ultrasound (EBUS)-derived cytology samples. METHODS: Samples were obtained from 55 consecutive patients with NSCLC who had undergone EBUS-transbronchial needle aspiration (TBNA) according to our standard clinical protocols. All tumours had been screened previously for epithelial growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. FISH, using commercially available ALK rearrangement-specific probes, was employed to assess ALK status. IHC using the ALK-1 monoclonal antibody (DAKO) was also performed. RESULTS: FISH analysis was successful in 52 of 55 samples (94.5%); ALK rearrangement was demonstrated in 3 of 52 samples from patients with NSCLC (5.7%). ALK amplification was observed in 3 of 52 patient samples (5.7%) and an increase in ALK copy number was found in 28 of 52 patient samples (53.8%). IHC on cell blocks demonstrated ALK expression in one of three samples with ALK rearrangement. One patient sample had concomitant ALK rearrangement and KRAS mutation. CONCLUSIONS: We found FISH to be superior to IHC using the ALK-1 monoclonal antibody for the detection of ALK rearrangement in EBUS-TBNA cytology specimens in NSCLC, and also that ALK rearrangement can co-exist with KRAS mutation in the same tumour.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Receptores Proteína Tirosina Quinases/genética , Adenocarcinoma/enzimologia , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Broncoscopia/instrumentação , Broncoscopia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Feminino , Humanos , Hibridização in Situ Fluorescente/instrumentação , Hibridização in Situ Fluorescente/métodos , Neoplasias Pulmonares/enzimologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
A 38-year-old primiparous woman presented with pre-eclampsia at 36 weeks gestation with an abnormal full blood count and leukoerythroblastic blood film. JAK2 V617F was negative and splenomegaly was noted on abdominal ultrasound. Delivery was at 37 weeks gestation by emergency caesarean section due to abnormal cardiotocography. Bone marrow aspirate and trephine confirmed a diagnosis of myelofibrosis. The case highlights a rare presentation of primary myelofibrosis in pregnancy, the difficulties in management, and the UK Obstetric Surveillance System who are collecting epidemiological data on uncommon disorders in pregnancy.
RESUMO
Seven cases were discussed by an expert panel at the 2009 Annual Scientific Meeting of the British Society of Haematology. These cases are presented in a similar format to that adopted for the meeting. There was an initial discussion of the presenting morphology, generation of differential diagnoses and then, following display of further presenting and diagnostic information, each case was concluded with provision of a final diagnosis.
Assuntos
Doenças Hematológicas/diagnóstico , Doenças Hematológicas/patologia , Adolescente , Adulto , Fenômenos Fisiológicos Sanguíneos , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: We describe a case of endolymphatic sac tumour confined to the middle ear, which radiologically mimicked a glomus tympanicum, in a 58-year-old woman with tinnitus. CASE REPORT: A 58-year-old woman presented with a one-year history of right-sided tinnitus. The clinical, radiological and surgical features were felt to be in keeping with a glomus tympanicum. However, the histopathological picture was that of a low grade papillary carcinoma of the endolymphatic sac, i.e. an endolymphatic sac tumour. CONCLUSION: Endolymphatic sac tumours are classically locally aggressive and centred around the petrous temporal bone. Further growth results in complete replacement of the mastoid and petrous pyramid by tumour. To the best of our knowledge, there have been no previous reports of an endolymphatic sac tumour located solely within the hypo- and epitympanum of the middle ear.
Assuntos
Carcinoma Papilar/diagnóstico , Neoplasias da Orelha/diagnóstico , Orelha Média , Saco Endolinfático , Carcinoma Papilar/cirurgia , Diagnóstico Diferencial , Neoplasias da Orelha/cirurgia , Feminino , Tumor de Glomo Timpânico/diagnóstico , Humanos , Terapia a Laser , Pessoa de Meia-Idade , Zumbido/etiologia , Resultado do TratamentoRESUMO
A morphology session is held each year at the Annual Scientific Meeting of the British Society of Haematology. Prior to the meeting this year, eight morphology cases were made available to BSH members as glass slides and also digitally as 'virtual slides'. A panel of invited commentators who had no prior knowledge of the diagnosis discussed the eight cases. An initial limited history and blood count are given with representative images from the case material; this is followed by the discussants' comments and suggested diagnosis. The actual clinical diagnosis is then given with other relevant information.
Assuntos
Hematologia , Adulto , Idoso , Anemia Refratária com Excesso de Blastos/patologia , Pré-Escolar , Técnicas de Laboratório Clínico , Análise Citogenética , Feminino , Testes Hematológicos , História do Século XXI , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/patologia , Masculino , EscóciaRESUMO
Interstitial deletion involving chromosome 4q12 generates the novel tyrosine kinase fusion protein encoded by FIP1L1-PDGFRA, which is present in many patients previously labelled as having hypereosinophilic syndrome, initially reported in 2003. Reports in recent literature document excellent clinical and molecular response to the tyrosine kinase inhibitor imatinib (Glivec). This report describes the case of a 58-year-old lady, diagnosed with FIP1L1-PDGFRA positive hypereosinophilic disorder, who subsequently developed symptoms related to an intracranial lesion. Biopsy and molecular genetic studies confirmed a diffuse infiltrative lesion, with evidence of FIP1L1-PDGFRA gene fusion. Initiation of imatinib treatment led to impressive clinical and radiological response.
Assuntos
Encefalopatias/genética , Síndrome Hipereosinofílica/genética , Proteínas de Fusão Oncogênica/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Benzamidas , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Feminino , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Mesilato de Imatinib , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and alpha-2 agonist (dexmedetomidine, DEX). Protocol 1: incremental phenylephrine was administered during control and combined GLY-DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2: muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY-DEX. Blood pressure was higher with GLY-DEX (99+/-3 mm Hg) and lower with TMP (78+/-3 mm Hg) relative to control (GLY-DEX: 90+/-2 mm Hg; TMP: 91+/-2 mm Hg; P<0.05). Incremental phenylephrine increased pressure during GLY-DEX (P<0.01 vs control) and TMP (P<0.01 vs control) to a similar degree. Both GLY-DEX and TMP infusion inhibited norepinephrine release (P<0.01 vs control). GLY-DEX inhibited baseline MSNA (P<0.05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Bloqueadores Ganglionares/administração & dosagem , Glicopirrolato/administração & dosagem , Trimetafano/administração & dosagem , Agonistas alfa-Adrenérgicos/administração & dosagem , Adulto , Bloqueio Nervoso Autônomo/métodos , Barorreflexo/efeitos dos fármacos , Barorreflexo/fisiologia , Débito Cardíaco/efeitos dos fármacos , Sistema Cardiovascular/inervação , Catecolaminas/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Antagonistas Muscarínicos/administração & dosagem , Fenilefrina/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
The leading region of the conjugal bacterial plasmid ColIb-P9 contains three dispersed repeats of a 328 bp sequence homologous to Frpo, a sequence from plasmid F that acts as a promoter in single-stranded DNA. One of these sequences, ssi3, inactive in the double-stranded form, promoted in vitro transcription exclusively from the single strand that is transferred during conjugation. Promoter activity was dependent on the presence of RNA polymerase holoenzyme containing sigma 70. Transcription initiated from the position predicted from folding the single-stranded DNA to form a pseudo double-stranded hairpin structure containing recognizable -35 and -10 promoter elements. Footprinting of RNA polymerase holoenzyme on single-stranded ssi3 DNA was consistent with this suggestion. Mutagenesis of the putative -35 region inactivated the promoter, but random mutations in the -10 region had little effect. The putative -10 region is a poor match to the consensus sequence and contains mismatched bases. Elimination of these mismatches invariably destroyed single-strand promoter activity. These observations reveal the crucial contribution of the unpaired bases in the -10 region in potentiating the formation of the productive open complex with RNA polymerase.
Assuntos
Plasmídeos de Bacteriocinas/genética , DNA de Cadeia Simples/fisiologia , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas , Sequências Repetitivas de Ácido Nucleico , Transcrição Gênica , Pareamento Incorreto de Bases , Conjugação Genética , Sequência Consenso , Pegada de DNA , DNA Bacteriano/genética , DNA Bacteriano/fisiologia , DNA de Cadeia Simples/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Fator F/genética , Regulação Bacteriana da Expressão Gênica , Mutação , Homologia de Sequência , Fator sigma/metabolismoRESUMO
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) can occur in patients maintained on immunosuppressive therapy following transplantation. This paper describes two cases of PTLD occurring in gingival tissues, in patients receiving ciclosporin following cardiac transplantation. TREATMENT: The lesions were localised to gingival tissues, mimicking ciclosporin-induced gingival overgrowth. They were removed surgically and the ciclosporin dose reduced to help prevent recurrence. CONCLUSION: The importance of histopathological examination of all tissue removed during routine gingivectomy procedures for ciclosporin-induced gingival overgrowth is highlighted.
Assuntos
Ciclosporina/efeitos adversos , Neoplasias Gengivais/diagnóstico , Crescimento Excessivo da Gengiva/induzido quimicamente , Transplante de Coração/efeitos adversos , Imunossupressores/efeitos adversos , Linfoma/diagnóstico , Diagnóstico Diferencial , Crescimento Excessivo da Gengiva/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Sickle cell/haemoglobin D-Punjab disease is a disorder with similar clinical features to sickle cell anaemia. This report describes the case of an 11 year old boy with this disease who was treated with regular transfusions from infancy. He underwent splenectomy at the age of 10 years for hypersplenism. Histology of the spleen revealed a striking pattern of heavy sinusoidal endothelial iron loading, with only moderate uptake by macrophages. Possible explanations for this unusual distribution of iron include phagocytosis of sickled erythrocytes by sinusoidal endothelial cells or direct endothelial iron uptake via transferrin receptors. Transfusion programmes ameliorate the symptoms of sickle cell disease but the dangers of iron overload should always be remembered.
Assuntos
Anemia Falciforme/complicações , Hemoglobinas Anormais/análise , Sobrecarga de Ferro/etiologia , Anemia Falciforme/terapia , Pré-Escolar , Humanos , Sobrecarga de Ferro/patologia , Masculino , Baço/patologia , Reação TransfusionalRESUMO
Enteropathy-type T-cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis for detection of mutations in exons 5-8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36%) ETLs, but not in UJ. Five of nine (56%) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25%) tumours with small- or medium-sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR-SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL.
Assuntos
Cromossomos Humanos Par 9/genética , Neoplasias Intestinais/genética , Perda de Heterozigosidade , Linfoma de Células T/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Humanos , Imunofenotipagem , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Doenças do Jejuno/genética , Doenças do Jejuno/metabolismo , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Polimorfismo Conformacional de Fita Simples , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Adult elite competitive rock climbers are small in stature with low body mass and very low body fat percentage. These characteristics have generated concern that young climbers may attempt body mass reduction to extreme levels with adverse consequences for health and performance. No published anthropometry data for young competitive climbers exist. OBJECTIVE: To describe the general anthropometric characteristics of junior US competitive rock climbers. METHODS: Ninety subjects (mean (SD) age 13.5 (3.0) years) volunteered to participate. All competed at the Junior Competition Climbers Association US National Championship. Anthropometric variables, including height, mass, body mass index (BMI), arm span, biiliocristal and biacromial breadths, skinfold thickness at nine anatomical sites, forearm and hand volumes, and handgrip strength, were measured. Selected variables were expressed as ratio values and as normative age and sex matched centile scores where appropriate. A control group (n=45) of non-climbing children and youths who participated in a variety of sports activities, including basketball, cross country running, cross country skiing, soccer, and swimming, underwent the same testing procedures in the Exercise Science Laboratory of Northern Michigan University. RESULTS: Mean (SD) self reported climbing ability was 11.80 (1.20), or about 5.11 d on the Yosemite decimal system scale. The mean (SD) experience level was 3.2 (1.9) years, and subjects competed in 10 (5) organised competitions over a 12 month period. Despite similarity in age, there were significant differences (p<0.01) between climbers and control subjects for height, mass, centile scores for height and mass, ratio of arm span to height ("ape index"), biiliocristal/biacromial ratio, sum of seven and sum of nine skinfolds, estimated body fat percentage, and handgrip/mass ratio. Despite significantly lower skinfold sums and estimated body fat percentage, no differences were found between climbers and controls for absolute BMI or BMI expressed as a centile score. CONCLUSIONS: Young competitive climbers have similar general anthropometric characteristics to elite adult climbers. These include relatively small stature, low body mass, low sums of skinfolds, and high handgrip to mass ratio. Relative to age matched athletic non-climbers, climbers appear to be more linear in body type with narrow shoulders relative to hips. Differences in body composition exist between climbers and non-climbing athletes despite similar BMI values.
Assuntos
Antropometria , Montanhismo/fisiologia , Adolescente , Composição Corporal , Estatura , Índice de Massa Corporal , Criança , Comportamento Competitivo , Feminino , Antebraço/anatomia & histologia , Força da Mão , Humanos , Masculino , Caracteres Sexuais , Dobras CutâneasRESUMO
Mantle cell lymphoma is characterized by the presence of the t(11;14)(q13;q32) translocation that causes over-expression of the BCL-1 gene and consequent overproduction of its gene product cyclin D1. We have developed a competitive fluorescent reverse transcription polymerase chain reaction assay for the detection and semiquantitation of cyclin D1 over-expression. Using this assay a definitive ratio of the expression of cyclin D1 to cyclins D2 and D3 can be determined, provided good quality RNA is available. A single upstream primer derived from a consensus sequence found in cyclins D1, D2, and D3 was labeled at the 5' end using a fluorescent dye. Downstream primers specific to cyclins D1 and D2 were designed and used in conjunction with a previously published D3 specific primer. The fluorescently labeled PCR products were separated by electrophoresis using an ABI 377 DNA sequencer. Fluorescence emitted from each product was used to determine the ratio of expression of cyclin D1 to D2 and D3 by assigning a dosage quotient [D1/(D2+D3)]. The mean dosage quotient recorded from samples representing 29 non-MCL patients was 0.03 (SD +/- 0.03), the maximum value being 0.11. Samples from eight patients with a diagnosis of MCL generated values greater than 2. Calculation of a dosage quotient using this competitive fluorescent reverse transcription polymerase chain reaction assay allows unequivocal identification of patients with over-expression of cyclin D1, providing a new tool for the differential diagnosis of MCL.
Assuntos
Ciclina D1/genética , Imunofluorescência/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Linfoma de Célula do Manto/genética , Proteínas Oncogênicas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Idoso , Idoso de 80 Anos ou mais , Ligação Competitiva , Ciclina D1/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Célula do Manto/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/metabolismo , RNA Mensageiro/análiseRESUMO
AIMS: Progressive changes have been reported in lymph nodes in HIV infection, but few accounts describe altered splenic histology at different stages of the disease. Investigation of splenic changes accompanying the progressive CD4+ T-cell depletion that occurs in HIV infection could shed light on normal immunological interactions in this organ. Therefore, we assessed the amount and distribution of lymphoid tissue in spleens from adults with documented early or advanced HIV disease. METHODS AND RESULTS: Immunohistochemistry was used to study splenic tissue collected in an extensive autopsy survey of HIV+ adults in West Africa. Compared with post-mortem spleens from HIV- West African adults and control UK spleens, those from HIV-infected patients showed severe atrophy of white pulp B- and T-cell compartments. In early and advanced HIV disease, marginal zone atrophy was significant. Peri-arteriolar lymphoid sheaths contained increased numbers of CD8+/CD45RO+ T-cells in advanced HIV disease. In red pulp, early and advanced cases showed a lymphocytosis of CD8+/CD45RO- T-lymphocytes. CONCLUSIONS: Atrophic changes were more extreme in advanced than early HIV infection. Reduced marginal zone function possibly explains the known predisposition of HIV+ patients to infection by encapsulated bacteria. Possible immunological consequences of these CD8+/CD45RO+ (peri-arteriolar lymphoid sheaths) and CD8+/CD45RO- (red pulp) responses deserve further study. Comparison of West African and UK control spleens indicated that there were no major ethnic differences in spleen structure to prevent extrapolation of our results to European adults.
Assuntos
Linfócitos T CD8-Positivos/patologia , Infecções por HIV/patologia , Linfocitose/patologia , Baço/patologia , Adolescente , Adulto , Atrofia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Côte d'Ivoire , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Técnicas Imunoenzimáticas , Antígenos Comuns de Leucócito/metabolismo , Linfocitose/etiologia , Linfocitose/imunologia , Pessoa de Meia-Idade , Tamanho do Órgão , Baço/metabolismo , Subpopulações de Linfócitos T/patologiaRESUMO
We conducted a retrospective study of treatment outcomes and survival in 120 consecutive, unselected patients with peripheral T-cell non-Hodgkin's lymphoma, presenting at a single centre over a 20-year period. Cases met the criteria of the Revised European-American Lymphoma (REAL) Classification and patients with peripheral T-cell lymphoma of the following subtypes were included: anaplastic large T-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILD), peripheral T-cell lymphoma unspecified (PTCLu), and intestinal T-cell lymphoma (ITCL). The study population consisted of 120 patients with a presenting diagnosis of peripheral T-cell lymphoma. Cases that had been previously confirmed as T-cell lymphoma at formal pathology review were identified from the lymphoma database of this institution. Staging investigations, treatment type and outcomes were taken from patient records. For each subtype, clinical characteristics, response to initial treatment, duration of response and any subsequent relapse were recorded. Overall, relapse, and progression-free survival figures were calculated. The ALCL group had the best response rate to first line treatment 19 of 22 (86 percent) while the AILD group had the lowest response 12 of 29 (41 percent). Relapse rates were PTCLu 13 of 35 (37 percent), ITCL 10 of 34 (29 percent), ALCL 6 of 22 (27 percent) and AILD 7 of 29 (24 percent). In terms of median overall survival, a significantly superior survival was demonstrated for the ALCL group (7.05 years) compared to the remaining three groups. The ALCL group had the lowest risk of death while the ITCL group had the highest risk (hazard ratio: 2.82). Five-year survival rates were estimated to be ALCL 60 percent, PTCLu 40 percent, AILD 30 percent and ITCL 25 percent. This single-centre study demonstrated different outcomes for each group with significant differences in overall survival rates. These findings support the clinical utility of the REAL lymphoma classification in respect to the PTCL subgroups included in this study.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/radioterapia , Adulto , Idoso , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Linfoma de Células T/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Estimates have been made of the reduction in dissolved oxygen levels in coastal waters that would result from the disposal of contaminated milk following a radiological accident. Two contrasting sites were chosen: the Bristol Channel near Hinkley Point and the coast of Cumbria near Sellafield. The results suggest that the dilution would be sufficiently strong near Hinkley Point, due to vigorous tidal mixing, that the impact on the DO levels of the coastal waters would be negligible. However, at both Sellafield and Heysham the disposal of milk could result in a reduction of the DO by 1-2 mg l(-1). In contrast to shallow estuarine waters, the recovery of oxygen levels due to the effects of re-aeration through surface gas exchange is unlikely to be significant due to the depth of the coastal waters. However, the recovery of the dissolved oxygen levels to ambient conditions following the completion of the discharge would occur on a time scale of about 17 days due to mixing of the DO deficit plume into the surrounding waters.