RESUMO
High foetal haemoglobin (HbF) levels are believed to ameliorate the manifestations of homozygous sickle cell (SS) disease. The corollary implies that patients with low HbF levels should have more severe clinical courses. We investigated this in a retrospective study of 50 Jamaican patients with steady-state HbF levels below 1% compared with a control group (A) of 54 subjects with steady-state HbF levels between 2.5 and 3.4% (around the 25th centile for our population), and a second control group (B) of 60 patients with steady-state HbF levels between 4.6 and 5.2% (around the 50th centile). Comparisons across the groups indicated significantly fewer females in the study group (16, 50 and 57%, respectively). Examination for haematological trends across the groups showed positive linear trends for haemoglobin (Hb) (P=0.004), packed cell volume (PCV) (P=0.01), mean cell volume (MCV) (P= < 0.001), mean cell haemoglobin (MCH) (P= < 0.001) and a negative trend for haemoglobin A2 (P=0.03). Clinically, there were no differences in the incidence of painful crises, abdominal crises and the acute chest syndrome, but leg ulcers were significantly less frequent in the study group (P=0.04). Therefore low HbF levels do not appear to increase the clinical severity of SS disease and may be protective against leg ulceration.
Assuntos
Anemia Falciforme/sangue , Hemoglobina Fetal/metabolismo , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Índices de Eritrócitos , Feminino , Hemoglobina Fetal/farmacologia , Seguimentos , Homozigoto , Humanos , Jamaica , Úlcera da Perna , Masculino , Dor , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The sickling disorders are a common cause of morbidity and mortality in Jamaica. Sickle cell beta+-thalassaemia is the fourth commonest form, occurring in one in every 3000 births. This is a heterogeneous condition, producing HbS, HbF and HbA2 with variable amounts of HbA, depending on the mutation and, within a defined population, only a few beta-thalassaemia mutations occur at high frequency. This study establishes the frequency of beta-thalassaemia mutations in Sbeta+-thalassaemia patients in Jamaica. In addition, comparison of the haematological phenotypes is possible by looking at the 'average steady-state haematology' of the different mutational groups. Blood samples from 132 unrelated Sbeta+-thalassaemia patients attending the MRC Sickle Cell Unit at the University of the West Indies were analysed by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) or sequencing to determine the nature and frequencies of the underlying beta-thalassaemia mutations. Ten mutations were identified, four of which accounted for 93% of patients studied. These were -29(A --> G) in 71 (54%), -88(C --> T) in 27 (20%), polyA(T --> C) in 17 (13%) and IVS1-5(G --> C) in nine (7%). The six remaining mutations found at low frequency were C24(T --> A) in two patients and one each of IVS2-848(C --> A), -90(C --> T), IVS1-5(G --> T), IVS1-5(G --> A) and IVS1-6 (T --> C). In one individual, no mutation was found. The three commonest mutations were all associated with haemoglobin levels of greater than 10 g/dl, whereas IVS1-5 (G --> C) had a more severe haematological phenotype. The predominance of -29(A --> G) and -88(C --> T) is in keeping with other studies on populations of African origin. IVS1-5(G --> C) is found chiefly in Indian populations, and all affected families acknowledged Indian ancestry, reflecting the prominent Indian community in Jamaica.
Assuntos
Desoxirribonucleases de Sítio Específico do Tipo II/genética , Mutação/genética , Talassemia beta/etnologia , Hemoglobina Fetal/genética , Globinas/genética , Humanos , Jamaica/etnologia , Polimorfismo Genético , Talassemia beta/genéticaRESUMO
The sickling disorders are a common cause of morbidity and mortality in Jamaica. Sickle cell betañthalassaemia is the fourth commonest form, occuring in one in every 3000 births. This is a heterogeneous condition, producing HbS, HbF and HbA2 with variable amounts of HbA, depending on the mutation and, within a defined population, only a few beta-thalassaemia mutations occur at high frequency. This study establishes the frequency of beta-thalassaemia mutations in Sbetañthalassaemia patients in Jamaica. In addition, comparison of the haematological phenotypes is possible by looking at the "average steady-state haematology" of the different mutational groups. Blood samples from 132 unrelated Sbetañthalassaemia patients attending the MRC Sickle Cell Unit at the University of the West Indies were analysed by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) or sequencing to determine the nature and frequencies of the underlying beta-thalassaemia mutations. Ten mutations were identified, four of which accounted for 93 percent of the patients studied. These were 29 (A --> G) in 71 (54 percent), -88 (C --> T) in 27 (20 percent), polyA (T --> C) in 17 (13 percent) and IVS1-5 (G --> C) in nine (7 percent). The six remaining mutations found at lower frequency were C24 (T --> A) in two patients and one each of IVS2-848 (C --> A), -90 (C --> T), IVS1-5 (G --> T),IVS1-6 (T --> C). In one individual, no mutation was found. The three commonest mutations were all associated with levels of greater than 10 g/dl, whereas IVS1-5 (G --> C) had a more severe haematological phenotype. The predominance of -29 (A --> G) and -88 (C --> T) is in keeping with other studies on populations of African origin. IVS1-5 (G --> C) is found chiefly in Indian populations, and all affected families acknowledged Indian ancestry, reflecting the prominent Indian community in Jamaica. (AU)
Assuntos
Humanos , Talassemia beta/etnologia , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Mutação/genética , Talassemia beta/genética , Hemoglobina Fetal/genética , Globinas/genética , Jamaica/etnologia , Polimorfismo GenéticoRESUMO
A study of the á-thalassaemia mutations by amplification refractory mutation system (ARMS) PCR of 130 Sá+ thalassaemia patients attending the sickle-cell clinic at the University of the West Indies revealed that 70 (53.9 percent) had the -29 (A to G) mutation, 23 (17.7 percent) had -88 (C to T), 19 (14.6 percent) had Poly A(AATAAA to AACAAA) and 2(1.5 percent) had C24 (T to A). In 16 (12.3 percent) patients we were unable to identify the mutations with the available primers. Of the three major groups, the -88 group had a higher foetal haemoglobin (HbF) than the -29 groups, who in turn had a higher haemoglobin (p<0.001). The -88 and -29 groups had a higher haemoglobin (p<0.01), a higher corrected haemoglobin A2(p<0.001), a higher calculated cell volume (p<0.001), a higher packed cell volume (p<0.01) and a higher mean cell volume (p<0.05) than the Poly A group. The -29 group also had fewer reticulocytes than the Poly A group (p<0.001). The difference in HbF levels could be a consequence of the thalassaemia mutations affecting the interaction of the á-globin gene to differing extents (AU)
Assuntos
Talassemia beta/genética , JamaicaRESUMO
Foram relatados diferenças na concentraçäo de alguns constituintes da saliva (esteroides, eletrólitos, glicose e enzimas) que ocorrem durante o ciclo menstrual e que talvez poderiam ser usados para predizer a ovulaçäo. Nos medimos estradiol, progesterona, glicose, sódio, potássio e cálcio em amostras da mistura salivar colhidas diariamente durante todo o ciclo menstrual. O dia da ovulaçäo foi determinado por ultra-sonografia e medidas de LH em urina. O perfil de estradiol e progesterona em saliva refletiu aquele classicamente encontrado em sangue. Os níveis dos eletrólitos em saliva näo mostraram padräo ciclíco definido mesmo após a correçäo da taxa de produçäo da saliva. Foram observadas alteraçöes cíclicas na concentraçäo de glicose em saliva, sendo que os valores máximos (picos) foram encontrados no dia ou no dia após a aovulaçäo, ou seja, durante o período periovulatório. Pequenos picos foram observados durante as fases folicular e lútea sem, entretanto, mostrarem um padräo reprodutivel. Estas alteraçöes foram melhor vistas nas amostras de jejum. Amostras sem o jejum tiveram concentraçöes altas de glicose o que tornou difícil a identificaçäo dos picos. Este estudo confirma o valor da medida dos esteróides em saliva, mas entretanto, sugere que medidas de glicose e eletrólitos em saliva têm, provavelmente, pouco valor como teste preditivo para ovulaçäo