RESUMO
OBJECTIVE: This study investigated mobile health enabled surveillance in ototoxicity. METHOD: This was a longitudinal study of 32 participants receiving chemotherapy. Baseline and exit audiograms that included conventional and extended high frequency audiometry were recorded within the patient's treatment venue using a validated mobile health audiometer. RESULTS: Average hearing thresholds at baseline were within the normal range (81.2 per cent left; 93.8 per cent right), reducing at exit testing (71.9 per cent left; 78.1 per cent right). Half of participants presented with a threshold shift according to ototoxicity monitoring criteria. The frequencies affected the most were between 4000 and 16 000 Hz, with left ears significantly more affected than right ears. Noise levels exceeded the maximum permissible ambient noise levels in up to 43.8 per cent of low frequencies (250-1000 Hz). CONCLUSION: Mobile health supported audiometry proved to be an efficacious tool for ototoxicity monitoring at the treatment venue. Changes in hearing ability over time could be tracked, improving surveillance in patients with full treatment schedules.
Assuntos
Antineoplásicos , Ototoxicidade , Humanos , Cisplatino/efeitos adversos , Antineoplásicos/efeitos adversos , Platina/efeitos adversos , Estudos Longitudinais , Ototoxicidade/etiologia , Audiometria , Audiometria de Tons Puros , Limiar AuditivoRESUMO
CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause DNA damage in vitro and in vivo. Single case reports have indicated a coincidence of PA with renal cell carcinoma and other tumors. However, the prevalence of benign and malignant neoplasms in patients with PA has not yet been studied. PATIENTS AND DESIGN: In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors was investigated in 335 patients with confirmed PA. Matched hypertensive subjects from the population-based Study of Health in Pomerania cohort served as controls. RESULTS: Of the 335 PA patients, 119 (35.5%) had been diagnosed with a tumor at any time, and 30 had two or more neoplasms. Lifetime malignancy occurrence was reported in 9.6% of PA patients compared to 6.0% of hypertensive controls (P = .08). PA patients with a history of malignancy had higher baseline aldosterone levels at diagnosis of PA (P = .009), and a strong association between aldosterone levels and the prevalence of malignancies was observed (P = .03). In total, 157 neoplasms were identified in the PA patients; they were benign in 61% and malignant in 25% of the cases (14% of unknown dignity). Renal cell carcinoma was diagnosed in five patients (13% of all malignancies) and was not reported in controls CONCLUSION: Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.
Assuntos
Aldosterona/sangue , Biomarcadores Tumorais/sangue , Hiperaldosteronismo/fisiopatologia , Hipertensão/fisiopatologia , Neoplasias/epidemiologia , Adulto , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/diagnóstico , Prevalência , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Proteínas de Neoplasias/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Neoplasias/análise , Sequência de Bases , Criança , Humanos , Antígenos CD15 , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Reação em Cadeia da PolimeraseRESUMO
Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.
Assuntos
Transplante de Medula Óssea , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Bussulfano/uso terapêutico , Feminino , Alemanha , Humanos , Interferon-alfa/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , PrognósticoRESUMO
To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow-up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Adulto , Transplante de Medula Óssea , Proteínas de Fusão bcr-abl/genética , Humanos , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance.
Assuntos
Linfoma de Burkitt/diagnóstico , Proteínas de Fusão bcr-abl/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Adulto , Linfoma de Burkitt/genética , Análise Citogenética/normas , Erros de Diagnóstico , Proteínas de Fusão bcr-abl/análise , Humanos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph(+) CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-alpha, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-alpha and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.
Assuntos
Antineoplásicos/administração & dosagem , Medula Óssea/patologia , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Biópsia , Transplante de Medula Óssea , Bussulfano/administração & dosagem , Aberrações Cromossômicas , Resistencia a Medicamentos Antineoplásicos , Feminino , Fibrose , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Falha de TratamentoRESUMO
Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph(+) chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-alpha therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-alpha +/- low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-alpha dose applied (P<0.000005). MF progressed during low-dose therapy (3 x 5 x 10(6) IU/week), but was prevented from progression when applying high dose (5 x 10(6) IU/m(2)/per day). MF disappeared when high-dose interferon-alpha was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-alpha on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-alpha with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-alpha. MF appears to be a significant early indicator of ineffective therapy in CML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Mielofibrose Primária/etiologia , Adulto , Biópsia , Aberrações Cromossômicas , Ensaios Clínicos Controlados como Assunto , Citarabina/administração & dosagem , Análise Citogenética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged >/=60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients >/=60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , Criança , Feminino , Seguimentos , Proteínas de Fusão bcr-abl , Humanos , Hidroxiureia/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We examined karyotypes and their prognostic significance in a series of 122 patients with chronic myeloid leukemia in blast crisis. Of 73 patients cytogenetically examined at the onset of blast crisis 63% had developed secondary cytogenetic abnormalities in addition to the Philadelphia chromosome. These newly emerging abnormalities included a double Philadelphia chromosome in 20 patients, a trisomy 8 in 17, and an isochromosome 17q in 11 patients. Development of such additional karyotypic abnormalities was significantly associated with a shorter median survival and less response to cytoreductive treatment and was significantly more common in nonlymphoid blast crisis than in the lymphoid-type blast crisis. Thus, assessment of karyotypes at the onset of chronic myeloid leukemia blast crisis appears to be of prognostic significance for both remission duration and survival.
Assuntos
Crise Blástica/genética , Aberrações Cromossômicas/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Crise Blástica/diagnóstico , Aberrações Cromossômicas/diagnóstico , Transtornos Cromossômicos , Feminino , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , PrognósticoRESUMO
Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.
Assuntos
Transplante de Medula Óssea , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Leucócitos , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Trombocitopenia/etiologia , Transplante HomólogoRESUMO
The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adolescente , Adulto , Southern Blotting , Medula Óssea/patologia , Transformação Celular Neoplásica/patologia , Citogenética , Feminino , Proteínas de Fusão bcr-abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Recombinação Genética , Indução de Remissão , Transcrição GênicaRESUMO
As opposed to standard polymerase chain reaction (PCR) using specific primers, genome analysis involving short random primers, for example RAPD, may yield inconsistent results if crude plant DNA preparations are used as the template. When RNase A, a thermostable enzyme, was added to such reactions, highly repeatable banding patterns were obtained from crude plant DNA, thus speeding up analyses substantially.
Assuntos
DNA de Plantas/genética , Reação em Cadeia da Polimerase/métodos , Ribonuclease Pancreático , Biotecnologia , DNA de Plantas/isolamento & purificação , Técnicas Genéticas , Árvores/genéticaRESUMO
From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.
Assuntos
Bussulfano/uso terapêutico , Hidroxiureia/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Feminino , Alemanha/epidemiologia , Alemanha Ocidental/epidemiologia , Humanos , Fatores Imunológicos/efeitos adversos , Interferon-alfa/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/mortalidade , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/terapia , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Suíça/epidemiologia , Resultado do TratamentoRESUMO
PURPOSE: The detection of long-term persistent chromosome aberrations in circulating haemopoietic stem cells after accidental radiation exposure. MATERIAL AND METHODS: Peripheral blood samples from highly exposed persons were collected 7-25 years after the radiation accidents in Moscow (1971), Kazan (1975) and Chernobyl (1996). Haemopoietic blood stem cells were analysed when investigating individual colonies derived from haemopoietic progenitor cells: burst-forming units-erythroid (BFU-E), granulocyte-macrophage-colony-forming cells (GM-CFC) and multipotent granulocyte-erythrocyte-macrophage- megakaryocyte-colony-forming cells (GEMM-CFC). Colony formation was obtained in methylcellulose cultures. Chromosome preparations in single colonies were performed using a microtechnique. RESULTS: Nine patients were investigated at 1 to 4 follow-up time points after radiation exposure. Three hundred and thirty-four single colonies were analyzed resulting in 1375 mitoses. It was found that colonies showed chromosome aberrations (ChA) up to 25 years after radiation exposure by classical cytogenetics and by fluorescence in situ hybridization (FISH). Stable aberrations were detected in 21% of colonies. They were clonal in 19% of colonies, i.e. the same abnormality was found in all cells derived from a single colony. In 2% of colonies ChA were stable but non-clonal; unstable ChA were not observed. CONCLUSIONS: The results indicate that blood-derived haemopoietic stem cells may serve as a biological indicator to detect radiation-induced ChA. Since they are considered to be in dynamic and functional exchange with stem cells in the medullary sites of blood cell formation such as bone marrow, the use of blood stem cells as a marker of radiation effects should be explored to assess the repair status of the stem cell pool as such.
Assuntos
Aberrações Cromossômicas , Células-Tronco Hematopoéticas/efeitos da radiação , Liberação Nociva de Radioativos , Adulto , Estudos de Casos e Controles , Bandeamento Cromossômico , Ensaio de Unidades Formadoras de Colônias , Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Moscou , Exposição Ocupacional , Federação Russa , Fatores de Tempo , UcrâniaRESUMO
Structural chromosome aberrations (SCAs) are sensitive indicators of a preceding exposure of the hematopoietic system to ionizing radiation. Cytogenetic investigations have therefore become routine tools for an assessment of absorbed radiation doses and their biological effects after occupational exposure or radiation accidents. Due to its speed and ease of use, fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes has become a method of choice to visualize SCAs. Until recently, this technique was limited to a rather small number of chromosomes, which could be tested simultaneously. As a result, only a fraction of the structural aberrations present in a sample could be detected and the overall dose effect had to be calculated by extrapolation. The recent introduction of two genome-wide screening techniques in tumor research, i.e., Spectral Karyotyping (SKY) and multicolor FISH (mFISH) now allows the detection of translocations involving any two non-homologous chromosomes. The present study was prompted by our desire to bring the power of mFISH to bear for the rapid identification of radiation-induced SCAs. We chose two model systems to investigate the utility of mFISH: lymphocytes that were exposed in vitro to 3 Gy photons and single hematopoietic progenitor cell colonies isolated from a Chernobyl victim 9 years after in vivo exposure to 5.4 Sv.In lymphocytes, we found up to 15 different chromosomes involved in rearrangements indicating complex radiation effects. Stable aberrations detected in hematopoietic cell colonies, on the other hand, showed involvement of up to three different chromosomes. These results demonstrated that mFISH is a rapid and powerful approach to detect and characterize radiation-induced SCAs in the hemopoietic system. The application of mFISH is expected to result in a more detailed and, thus, more informative picture of radiation effects. Eventually, this technique will allow researchers to rapidly delineate chromosomal breakpoints and facilitate the identification of the genes involved in radiation tumorigenesis.
Assuntos
Aberrações Cromossômicas , Células-Tronco Hematopoéticas/efeitos da radiação , Linfócitos/efeitos da radiação , Adulto , Bandeamento Cromossômico , Coloração Cromossômica , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Cariotipagem , Linfócitos/citologia , Linfócitos/metabolismo , MasculinoRESUMO
BACKGROUND: This study compared vestibulocollic reflex and vestibulo-ocular reflex functioning in subjects with and without human immunodeficiency virus. It also described test results throughout progression of the disease and compared the results of human immunodeficiency virus positive subjects who were receiving antiretroviral therapies with those not receiving this treatment. METHODS: Subjects comprised 53 adults with human immunodeficiency virus (mean age 38.5 ± 4.4 years) and 38 without human immunodeficiency virus (mean age 36.9 ± 8.2 years). Clinical examinations included cervical vestibular-evoked myogenic potential and bithermal caloric testing. RESULTS: Abnormal cervical vestibular-evoked myogenic potential and caloric results were significantly higher in the human immunodeficiency virus positive group (p = 0.001), with an odds ratio of 10.2. Vestibulocollic reflex and vestibulo-ocular reflex involvement increased with progression of the disease. There were more abnormal test results in subjects receiving antiretroviral therapies (66.7 per cent) than in those not receiving antiretroviral therapies (63.6 per cent), but this difference was insignificant. CONCLUSION: Human immunodeficiency virus seems to influence vestibulocollic reflex pathways. Combining cervical vestibular-evoked myogenic potential and caloric testing may be useful to detect early neurological involvement in human immunodeficiency virus positive subjects.
Assuntos
Soropositividade para HIV/complicações , Reflexo Vestíbulo-Ocular/fisiologia , Doenças Vestibulares/fisiopatologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos de Casos e Controles , Progressão da Doença , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Potenciais Evocados Miogênicos Vestibulares , Adulto JovemRESUMO
Objective: To characterise auditory involvement secondary to excessive craniotubular bone growth in individuals with sclerosteosis in South Africa. Methods: This cross-sectional study assessed the auditory profile of 10 participants with sclerosteosis. An auditory test battery was used and results for each ear were recorded using descriptive and comparative analyses. Results: All participants presented with bilateral, mixed hearing losses. Of the 20 ears, hearing loss was moderate in 5 per cent (n = 1), severe in 55 per cent (n = 11) and profound in 40 per cent (n = 8). Air-bone gaps were smaller in older participants, although the difference was not statistically significant (p > 0.05). Computed tomography scans indicated pervasive abnormalities of the external auditory canal, tympanic membrane, middle-ear space, ossicles, oval window, round window and internal auditory canal. Narrowed internal auditory canals corresponded to poor speech discrimination, indicative of retrocochlear pathology and absent auditory brainstem response waves. Conclusion: Progressive abnormal bone formation in sclerosteosis involves the middle ear, the round and oval windows of the cochlea, and the internal auditory canal. The condition compromises conductive, sensory and neural auditory pathways, which results in moderate to profound, mixed hearing loss.
Assuntos
Pinus/genética , Cruzamentos Genéticos , Desastres , Biologia Molecular/métodos , Pinus/fisiologia , ÁrvoresRESUMO
INTRODUCTION: Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear. OBJECTIVE: To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome. METHOD: Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched. RESULTS: We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study. DISCUSSION: We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. CONCLUSION: Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life.