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1.
Vasc Health Risk Manag ; 18: 27-42, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35210781

RESUMO

PURPOSE: Chronic myeloid leukemia (CML) is one of the common hematological malignancies in Nigeria. Cardiac abnormalities are associated with CML irrespective of treatment with tyrosine kinase inhibitors such as imatinib, which is available gratis in Nigeria. OBJECTIVE: To assess the prevalence and patterns of cardiac dysfunction among patients with CML irrespective of treatment with imatinib using transthoracic echocardiography, and 12-lead surface electrocardiography. PATIENTS AND METHODS: CML patients without Imatinib, CML patients with imatinib, and apparently healthy (age- and sex-matched) controls were 70 each in the study. Various echocardiographic parameters were measured and data obtained were analyzed, and the level of significance was taken as p < 0.05. RESULTS: Of 70 CML patients with imatinib, 54.3% were men and 45.7% were women, while the CML group without imatinib had 62.9% men and 37.1% women, non-CML control had 54.3% men and 45.7% women. The average hematocrit was significantly lower in the CML group without Imatinib compared with the other groups (p<0.001). And, 12.9% and 17.1% of CML groups with and without imatinib had LVH, respectively, and none of the non-CML controls had LVH (P<0.041). Impaired left ventricular relaxation in 25.71% and 28.57% of CML patients with and without imatinib respectively but only 8.57% of the non-CML control had impaired left ventricular relaxation (p=0.236). Mitral valve regurgitation was the most frequent valvular abnormality across the groups. Pulmonary hypertension in 17.4% and 20% of CML patients with and without imatinib, respectively, but none of the non-CML controls had pulmonary hypertension (p<0.001). Pericardial effusion in 32.86% and 45.71% of CML patients with and without imatinib, respectively, but none of the non-CML controls had pericardial effusion (p<0.001). There was no significant difference in the QTC interval across the three groups. CONCLUSION: Cardiac abnormalities are present in CML patients with or without Imatinib treatment, with significant prevalence than what is seen in the non-CML control group.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/efeitos adversos , Ecocardiografia , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Nigéria , Inibidores de Proteínas Quinases/efeitos adversos
2.
J Med Case Rep ; 15(1): 504, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625105

RESUMO

BACKGROUND: The occurrence of acute leukemia in patients with sickle cell anemia is uncommon. The Philadelphia chromosome is the hallmark of chronic myeloid leukemia. However, it may also be associated with acute lymphoblastic leukemia and acute myeloblastic leukemia. The common BCR-ABL1 transcripts seen in acute lymphoblastic leukemia are e1a2, e13a2, and e14a2, while other transcripts such as e1a3, e13a3, and e6a2 occur rarely. This report describes the presentation, management, and outcome of the occurrence of B-cell acute lymphoblastic leukemia with the rare e1a3 BCR-ABL1 transcript in a patient with sickle cell anemia. CASE PRESENTATION: A 19-year-old male Nigerian, a known sickle cell anemia patient was admitted on account of severe vaso-occlusive crisis. Examination revealed fever, palor, and jaundice. Full blood count showed anemia and leukocytosis. Peripheral blood and bone marrow smears revealed numerous large and small lymphoblasts in keeping with the L2 subtype of acute lymphoblastic leukemia based on the French-American-British classification. Further evaluation was in keeping with a diagnosis of BCR-ABL1-positive mature B-cell acute lymphoblastic leukemia associated with the rare e1a3 transcript. He was commenced simultaneously on induction chemotherapy and Imatinib while being prepared for allogeneic stem cell transplantation. However, he died  six  months after diagnosis from meningoencephalitis. CONCLUSION: The occurrence of acute lymphoblastic leukemia with a rare BCR-ABL1 e1a3 transcript in association with sickle cell anemia is uncommon and associated with poor prognosis.


Assuntos
Anemia Falciforme , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/genética , Linfócitos B , Proteínas de Fusão bcr-abl/genética , Humanos , Masculino , Nigéria , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto Jovem
3.
Infect Agent Cancer ; 16(1): 36, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030716

RESUMO

BACKGROUND: The present study aimed to classify lymphoid neoplasms according to the latest World Health Organization (WHO) classification and outlining the distribution in Nigeria of different entities. Additionally, the study describes the prevalence of lymphoid neoplasms associated with Epstein-Barr virus (EBV) infection in the Nigerian population. METHODS: We collected 152 formalin-fixed paraffin-embedded (FFPE) tissues diagnosed as lymphoma from 2008 to 2018, coming from three different institutions located within three geopolitical zone in Nigeria. These institutions included the University College Hospital (UCH), Ibadan, Oyo State, the Enugu State University of Science and Technology Teaching Hospital (ESUTH), Enugu, Enugu State, and the Meena Histopathology and Cytology Laboratory (MHCL), Jos, Plateau State. RESULTS: From the total 152 cases retrieved, 50 were excluded due to insufficient tissue materials or inconclusive antigen reactivity. We confirmed 66 (64.7%) cases as lymphomas out of the remaining 102 FFPE with a male to female ratio of 2:1 and a mean age of 44.4 years. Ten entities were identified, and of these, chronic lymphocytic leukemia (CLL) was the most prevalent category (34.8%). For the diffuse large B-cell lymphomas not otherwise specified (DLBCL, NOS), the germinal centre B-cell type was the most common (71.4%). Ten lymphoma cases (15.2%) were positive for Epstein-Barr virus (EBV), most of which were Hodgkin lymphoma (HL). CLL was common in the Hausa ethnic group, HL in the Yoruba ethnic group, while the Igbo ethnic group had an equal distribution of CLL, HL, and DLBCL diagnosis. CONCLUSION: Although the distribution of lymphomas in Nigeria shares some similarities with those of other countries, we described distinct features of some subtypes of lymphomas. Also, the study underscores the need for a more precise diagnosis and classification of lymphoid neoplasms in Nigeria using the latest WHO classification.

4.
Indian J Hematol Blood Transfus ; 36(4): 646-651, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100706

RESUMO

The distribution of BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") in Nigerians with chronic myeloid leukemia (CML) had not been previously studied. In addition, there is paucity of data on the impact of BCR-ABL1 transcript variants on clinical presentation and survival in CML patients in Nigeria. The BCR-ABL1 transcript variants were analyzed in 230 Imatinib-treated CML patients at diagnosis. Patients with incomplete data (n = 28), e19a2 (n = 3) and e1a2 (n = 1) were excluded from analysis of transcript variant on disease presentation and survival leaving only 198. The frequencies of BCR-ABL1 transcript variants were 30 (13.0%), 114 (49.6%), 82 (35.7%), three (1.3%) and one (0.4%) for e13a2, e14a2, co-expression of e13a2/e14a2, e19a2 and e1a2, respectively. A significantly higher platelet count was found in patients with e13a2 variant (531.1 ± 563.4 × 109/L) than in those expressing e14a2 (488.2 ± 560.3 × 109/L) or e13a2/e14a2 (320.7 ± 215.8 × 109/L); p = 0.03. No significant differences were found between the variants with regards to gender, age, phase of disease at diagnosis, total white blood cell count, neutrophil percentage, hematocrit, splenomegaly or hepatomegaly. Overall survival was higher but not statistically significant (p = 0.4) in patients with e14a2 variant (134 months) than in e13a2 (119 months) and co-expression of e13a2/e14a2 (115 months). Nigerian CML patients have the highest incidence of co-expression of e13a2 and e14a2. Distinct disease characteristics which contrast with findings from the Western countries were also identified in Nigerians which may be due to genetic factors.

5.
Leuk Lymphoma ; 60(1): 216-221, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741432

RESUMO

Imatinib has been successful in the management of chronic myeloid leukemia (CML) but some patients experience adverse reactions or develop resistance to its use. The roles of some polymorphisms in genes encoding enzymes critical for the biotransformation of imatinib have been previously examined. This study, hence, evaluated some other unstudied functionally significant polymorphisms in CYP1A2, CYP2C8, CYP2C9, and CYP3A5. Trough imatinib blood levels and genotypes were determined in 42 CML patients by an HPLC-UV technique and a Sequenom iPLEX assay, respectively. Statistical analysis of the influence of genetic polymorphisms on standardized trough level detected no significant relationship. However, higher trough levels were observed in two homozygous carriers of CYP2C8*2 while diminished imatinib levels were seen in two homozygous carriers of CYP3A5*7. The study findings suggest that polymorphisms in drug metabolizing enzymes may be significant for imatinib therapy only in instances where all copies of the relevant studied genes are functionally impaired.


Assuntos
Antineoplásicos/farmacocinética , Variação Biológica da População/genética , Mesilato de Imatinib/farmacocinética , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biotransformação , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2C8/metabolismo , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/genética , Masculino , Pessoa de Meia-Idade , Nigéria , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Adulto Jovem
6.
J Clin Pharmacol ; 57(12): 1554-1563, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28618035

RESUMO

Imatinib, a tyrosine kinase inhibitor, is the drug of choice for the treatment of chronic myeloid leukemia in Nigeria. Several studies have established interindividual and interpopulation variations in imatinib disposition although no pharmacokinetic study have been conducted in an African population since the introduction of the drug. This study explored a population pharmacokinetic approach to investigate the disposition of imatinib in Nigerians and examined the involvement of some covariates including genetic factors in the variability of the drug disposition with a view to optimize the use of the drug in this population. A total of 250 plasma concentrations from 126 chronic myeloid leukemia patients were quantified using a validated method. A population pharmacokinetic model was fitted to the data using NONMEM VII software, and the influences of 12 covariates were investigated. The mean population-derived apparent steady-state clearance, elimination half-life, area under the concentration-time curve over 24 hours, and volume of distribution were 17.2 ± 1.8 L/h., 12.05 ± 2.1 hours, 23.26 ± 0.6 µg·h/mL, and 299 ± 20.4 L, respectively. Whole blood count, ethnicity, CYP3A5*3, and ABCB1 C3435T were found to have significant influence on the apparent clearance, while the interindividual variability in clearance and interoccasion variability in bioavailability were 17.4% and 20.4%, respectively. There was a wide variability in apparent clearance and area under the curve compared to those reported in other populations. Thus, treatment with a standard dose of imatinib in this population may not produce the desired effect in most of the patients, whereas continuous exposure to a low drug concentration could lead to pharmacokinetic-derived resistance. The authors suggest the need for therapeutic drug monitoring-guided dose individualization in this population.


Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Mesilato de Imatinib/farmacocinética , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Modelos Biológicos , Adolescente , Adulto , População Negra , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Reprodutibilidade dos Testes , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-27375361

RESUMO

OBJECTIVES: The advent of the tyrosine kinase inhibitors has markedly changed the prognostic outlook for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia (CML). This study was designed to assess the overall survival (OS) of Nigerian patients with CML receiving imatinib therapy and to identify the significant predictors of OS. METHODS: All patients with CML receiving imatinib from July 2003 to June 2013 were studied. The clinical and hematological parameters were studied. The Kaplan-Meier technique was used to estimate the OS and median survival. P-value of <0.05 was considered as statistically significant. RESULTS: The median age of all 527 patients (male/female = 320/207) was 37 (range 10-87) years. There were 472, 47, and 7 in chronic phase (CP), accelerated phase, and blastic phase, respectively. As at June 2013, 442 patients are alive. The median survival was 105.7 months (95% confidence interval [CI], 91.5-119.9); while OS at one, two, and five years were 95%, 90%, and 75%, respectively. Multivariate Cox regression analysis revealed that OS was significantly better in patients diagnosed with CP (P = 0.001, odds ratio = 1.576, 95% CI = 1.205-2.061) or not in patients with anemia (P = 0.031, odds ratio = 1.666, 95% CI = 1.047-2.649). Combining these variables yielded three prognostic groups: CP without anemia, CP with anemia, and non-CP, with significantly different median OS of 123.3, 92.0, and 74.7 months, respectively (χ (2) = 22.042, P = 0.000016). CONCLUSION: This study has clearly shown that for Nigerian patients with CML, the clinical phase of the disease at diagnosis and the hematocrit can be used to stratify patients into low, intermediate, and high risk groups.

8.
Niger J Med ; 25(1): 60-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29963822

RESUMO

Background: Individuals with sickle cell anaemia (SCA) have lower systemic blood pressures compared to individuals with haemoglobin Hb AA phenotype. Objective: Seventy-nine (79) individuals with SCA (subjects) in steady state and 50 age-matched individuals with Hb AA (controls) were prospectively studied. Height, blood pressure (BP), weight, creatinine clearance (by 24-hour urine collection), full blood count (FBC) and reticulocyte count were obtained from all subjects and controls. Body mass index (BMI), corrected reticulocyte count, mean arterial pressure (MAP) and pulse pressure (PP) were calculated using standard protocols.The frequency of vaso-occlusive crises in the last one year and number of blood transfusions in the last two years were obtained from subjects. Data was analyzed using descriptive and inferential statistics and p ≤0.05 was used to define the level of statistical significance. Methodology: Seventy-nine (79) individuals with SCA (subjects) in steady state and 50 age-matched individuals with Hb AA (controls) were prospectively studied. Height, blood pressure (BP), weight, creatinine clearance (by 24-hour urine collection), full blood count (FBC) and reticulocyte count were obtained from all subjects and controls. Body mass index (BMI), corrected reticulocyte count, mean arterial pressure (MAP) and pulse pressure (PP) were calculated using standard protocols.The frequency of vaso-occlusive crises in the last one year and number of blood transfusions in the last two years were obtained from subjects. Data was analyzed using descriptive and inferential statistics and p ≤0.05 was used to define the level of statistical significance. Results: The systolic (105.52±11.75mmHg and 113.20±7.94mmHg respectively; P = 0.01), diastolic (62.59±9.33mmHg and 75.40±5.70mmHg respectively; P=0.03) and mean arterial pressures (76.90±8.81mmHg and 88.00±5.51mmHg respectively; P =0.04) were significantly lower in subjects when compared with controls. ; pulse pressure (PP) was however significantly higher in subjects than controls (42.92±10.91mmHg and 37.80±7.43mmHg respectively (P = 0.03). In female subjects, the white cell count was negatively correlated with systolic BP (r = -0.39;P = 0.01) and PP (r = -0.33; P = 0.03). Conclusion: Lower systolic and pulse pressures may predict worsening disease severity in individuals with sickle cell anaemia.


Assuntos
Anemia Falciforme/fisiopatologia , Pressão Arterial/fisiologia , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/terapia , Pressão Sanguínea/fisiologia , Transfusão de Sangue/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Prognóstico , Fatores Sexuais , Adulto Jovem
9.
Adv Hematol ; 2015: 908708, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26435715

RESUMO

Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML. Methods. All adult patients on imatinib (400-600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20-75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques. Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%. Conclusion. Imatinib's place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations.

10.
J Clin Diagn Res ; 9(6): EC14-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26266128

RESUMO

BACKGROUND: The proper histopathological characterization of malignant lymphomas requires the use of immunohistochemistry along with other molecular pathology techniques. MATERIALS AND METHODS: Malignant lymphomas histologically diagnosed in our hospital were reclassified according to the WHO scheme using immunohistochemistry while in-situ hybridization was performed for the detection of Epstein-Barr virus encoded RNA. RESULTS: There were 83 cases of lymphoma. The male to female ratio was 1.9:1 while the overall mean age was 41.7 years. Non-Hodgkin lymphomas (NHL) constituted about 79.5% of cases. The majority of cases (98.8%) were B-cell lymphomas. Nine subtypes of lymphomas were identified with diffuse large B-cell lymphomas (56.4% of which were of the germinal centre type) constituting the largest group (47.0%). Intermediate and high grade subtypes were more common. The majority of cases (72.3%) were nodal lymphomas with cervical lymph node being the commonest site (48.2%). Only classical Hodgkin lymphoma (HL) (20.5%) was seen of which the mixed cellularity subtype was the most common. Epstein Barr virus (EBV) encoded ribonucleic acid was detected in 7 cases (8.4%) including 4 cases of HL, 2 cases of Burkitt lymphoma and the only case of plasmablastic lymphoma. About five cases were reclassified as non-lymphoid malignant lesions. CONCLUSION: Immunohistochemistry is vital to the proper classification of lymphomas even in a resource poor environment. Although nine subtypes of lymphomas were identified, diffuse large B-cell lymphomas formed the largest single group. Epstein-Barr virus probably plays an important role in lymphomatogenesis in this environment. A larger multicentre study is required to prove this.

11.
Med Princ Pract ; 23(3): 271-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24751459

RESUMO

OBJECTIVE: To study degrees of chronic kidney disease (CKD) using creatinine clearance in adult Nigerian patients with sickle-cell disease (SCD). METHODS: One hundred SCD patients, made up of 79 HbSS (homozygous haemoglobin S) patients and 21 HbSC (heterozygous haemoglobins S and C) patients, were investigated prospectively, along with 50 normal controls. Their sociodemographic data, weight and drug history were documented. Each participant underwent dipstick urinalysis, and creatinine clearance was calculated following a 24-hour urine collection and serum creatinine measurement. They were categorized into stages of CKD based on the creatinine clearance. RESULTS: Of the 79 HbSS patients, 14 (18%), 28 (35%), 33 (42%) and 4 (5%) had stage 1, 2, 3 and 4 CKD, respectively. In the HbSC group, 3 (14%), 9 (43%) and 9 (43%) patients had stage 1, 2 and 3 CKD, respectively. Proteinuria was noted in 16 (20%) HbSS patients but not in any of the HbSC patients. Of the subjects aged ≤24 years (n = 49), 9 (18%), 18 (37%), 21 (43%) and 1 (2%) had stage 1, 2, 3 and 4 CKD, respectively. Of those aged >24 years (n = 51), 8 (16%), 19 (37%), 21 (41%) and 3 (6%) had stage 1, 2, 3 and 4 CKD, respectively. None of the subjects had stage 5 CKD. CONCLUSION: In this study, the adult subjects with SCD had various degrees of CKD. Adequate follow-up and active intervention are advocated to delay the onset of end-stage nephropathy.


Assuntos
Anemia Falciforme/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Creatinina/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Nigéria/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Urinálise
12.
Breast J ; 19(5): 470-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23865786

RESUMO

The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily (2,000 mg/m(2) total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11-59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20-70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand-foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Terapia Neoadjuvante , Adulto , Idoso , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Estudos de Viabilidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Nigéria
13.
Br J Haematol ; 158(6): 749-62, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22844968

RESUMO

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Adolescente , Adulto , África Subsaariana/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patologia , Causas de Morte , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Mesna/administração & dosagem , Mesna/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Indução de Remissão , Risco , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
14.
Br J Haematol ; 154(6): 696-703, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21707579

RESUMO

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub-Saharan African centres is presented. Among children (<18 years of age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub-Saharan Africa for fostering high-quality translational research.


Assuntos
Linfoma/diagnóstico , Linfoma/epidemiologia , Melhoria de Qualidade , Pesquisa Translacional Biomédica/métodos , África Subsaariana/epidemiologia , Atenção à Saúde/normas , Gerenciamento Clínico , Humanos , Cooperação Internacional , Linfoma/terapia
15.
J Natl Cancer Inst ; 103(7): 553-61, 2011 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-21422402

RESUMO

BACKGROUND: Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. PATIENTS AND METHODS: Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ(2) distribution. All statistical tests were two-sided. RESULTS: A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. CONCLUSIONS: In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Benzamidas , Esquema de Medicação , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Reação em Cadeia da Polimerase , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
16.
Arch Environ Occup Health ; 65(1): 27-33, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20147000

RESUMO

The blood of 76 cacao farmers from Southwestern Nigeria was monitored for erythrocyte cholinesterase enzyme activity (AChE) and hemoglobin values before and after insecticide application. Eight farmers had 30% to 50% baseline AChE activity, which suggests chronic organophosphate insecticide poisoning. AChE activity inhibition suggestive of occupational exposure (20% to 30%) was manifested by 28% of the farmers, whereas 30% to 50% inhibition suggestive of hazard was manifested by 11%. Significantly depressed post-insecticide application hemoglobin values were similarly recorded among the farmers. AChE activity inhibition, depression in hemoglobin values, and the years of involvement of the farmers in insecticide application on cacao, were positively correlated. Occupational exposure hazard due to organophosphate insecticides is therefore real among cacao farmers in Southwestern Nigeria. Regular biomonitoring of their blood for AChE activity and hemoglobin level is necessary.


Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Colinesterases/sangue , Eritrócitos/enzimologia , Hemoglobinas/efeitos dos fármacos , Inseticidas/toxicidade , Exposição Ocupacional/efeitos adversos , Acetilcolinesterase/sangue , Doenças dos Trabalhadores Agrícolas/sangue , Doenças dos Trabalhadores Agrícolas/epidemiologia , Agricultura , Cacau , Inibidores da Colinesterase/toxicidade , Eritrócitos/efeitos dos fármacos , Humanos , Nigéria/epidemiologia , Compostos Organofosforados/toxicidade , Estatística como Assunto
17.
J Health Care Poor Underserved ; 21(1 Suppl): 11-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20173281

RESUMO

We assessed the efficacy of a pilot questionnaire designed to elicit information about external risk factors for breast cancer in sub-Saharan African women. Preliminary analysis identified areas of the questionnaire and interviewing process that required modification, as well as socioeconomic factors that contribute to reduced participation among these understudied populations.


Assuntos
Neoplasias da Mama/epidemiologia , Inquéritos e Questionários , Adulto , África Subsaariana/epidemiologia , Estudos de Casos e Controles , Coleta de Dados/métodos , Feminino , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Participação do Paciente , Projetos Piloto , Projetos de Pesquisa , Fatores de Risco , População Rural , Fatores Socioeconômicos
18.
J Microbiol Immunol Infect ; 42(1): 69-73, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19424561

RESUMO

BACKGROUND AND PURPOSE: Lupus anticoagulants (LACs) are frequently found in patients with human immunodeficiency virus (HIV). This study was designed to examine the prevalence of LACs and its significance in HIV-infected Nigerian patients. METHODS: LACs were assayed, and complete blood count and direct Coombs' test (DCT) were performed for 155 participants. Patients with other conditions known to be associated with LACs such as autoimmune disease, pregnancy, malignancies, and illegal drug use were excluded. There were 104 highly active antiretroviral therapy-naive patients with HIV and 51 HIV-negative control participants. RESULTS: The prevalences of LACs in HIV-infected patients and controls were 2.9% and 1.9%, respectively (p = 0.973). The majority of the patients (76%) had clinical and/or immunological acquired immunodeficiency syndrome. The mean (+/- standard deviation) hematocrit levels of patients (0.32 +/- 0.05) were significantly lower than those of the controls (0.40 +/- 0.04) [p <0.0001]. Although within the normal range, the platelet count of HIV-infected patients (180 +/- 667 x 10(9)/L) was significantly lower than that of the controls (213 +/- 80 x 10(9)/L) [p = 0.026]. None of the participants had neutropenia or DCT-positivity. There was no correlation between LAC and opportunistic illness, thrombosis, or cytopenia. CONCLUSIONS: The prevalence of LACs was low and was not associated with opportunistic illness, thrombosis, or cytopenia.


Assuntos
Infecções por HIV/complicações , Inibidor de Coagulação do Lúpus/sangue , Adulto , Idoso , Anemia , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia , Nigéria , Tempo de Tromboplastina Parcial , Trombocitopenia , Trombose
19.
J Natl Med Assoc ; 101(4): 361-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19397228

RESUMO

BACKGROUND: This study describes the pattern of idiopathic infranuclear facial palsy (facial neuropathy) and highlights the role of human immunodeficiency virus (HIV)/AIDS in its occurrence and management. PATIENTS AND METHODS: This study conducted in Ile-Ife, Nigeria, assessed individuals with idiopathic facial neuropathy seen at the neurology; maxillofacial surgery; and ear, nose and throat outpatient clinics between 1994 and 2006. RESULTS: Eighty-eight patients with idiopathic facial neuropathy were seen during the 13-year study period. Forty-six (52.3%) were males, and the age range was 15 to 76 years, with a median of 35.5 years and interquartile range of 24.5 to 54 years. The right side was affected in 59.1%, compared with 40.9% on the left side. Twenty-six patients (29.5%) were HIV positive at presentation: 16 males, 10 females; mean age for HIV-positive patients was 29.15 +/- 8.12 years and 44.39 +/- 18.48 years for HIV-negative patients. There was a significant relationship among the status of the patients and the severity at presentation (p = .035), treatment given (p = .019), and the occurrence of flu-like symptoms (p = .004). CONCLUSION: A high index of suspicion of seroconversion is essential in patients presenting with idiopathic facial neuropathy since it has implications for management. Serological testing for HIV, especially in patients at risk and those with history of recent flu-like symptoms, is recommended.


Assuntos
Paralisia de Bell/virologia , Infecções por HIV/complicações , HIV-1 , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Paralisia de Bell/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Prognóstico , Inquéritos e Questionários , Adulto Jovem
20.
Chemosphere ; 72(5): 781-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18471864

RESUMO

The blood serum of cacao farmers and their domestic water sources were analyzed for insecticide residues in selected cacao growing communities of Southwestern Nigeria. The farmers were grouped into five exposure periods based on their years of involvement in insecticide application, viz, <5 years, 5-9 years, 10-14 years, 15-19 years and >20 years. The residue analyses revealed that 42 out of the 76 farmers had residues of diazinon, endosulfan, propoxur and lindane in their blood; and 47.6% out of these farmers belonged in the >20 years exposure duration period. About 34% of the farmers had diazinon with a mean concentration of 0.067 mg kg(-1), 29% endosulfan (mean=0.033 mg kg(-1)), 23% propoxur (mean=0.095 mg kg(-1)), and 17% lindane (mean=0.080 mg kg(-1)) in their blood. The residues of lindane, endosulfan and propoxur in all the exposure duration categories were found to be far below the no observable adverse effect level (NOAEL) while diazinon residues detected in the blood serum of the farmers in all the exposure duration categories exceeded the NOAEL of 0.02 mg kg(-1) for the insecticide. The study also revealed that the sources of drinking water had been contaminated with dazinon and propoxur in some of the farmers' localities; and the concentrations of the insecticides exceeded the acceptable daily intake (ADI). It is concluded that cacao farmers in Southwestern Nigeria may have been occupationally exposed due to insecticide application for mirid control in their cacao plantations; and the exposure at times is of such magnitude as to be hazardous to the farmers and their respective communities.


Assuntos
Agricultura , Cacau , Inseticidas/análise , Inseticidas/sangue , Exposição Ocupacional/análise , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/sangue , Abastecimento de Água/análise , Adulto , Feminino , Humanos , Masculino , Nigéria , Nível de Efeito Adverso não Observado , Manejo de Espécimes
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