Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.     

T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking

Background  

The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs.     

The clinical spectrum of homozygous HOXA1 mutations

We describe nine previously unreported individuals from six families who have homozygous mutations of HOXA1 and either the Bosley-Salih-Alorainy syndrome (BSAS) or the Athabascan brainstem dysgenesis syndrome (ABDS). Congenital heart disease was present in four BSAS patients, two of whom had neither deafness nor horizontal gaze restriction, thus raising the possibility that cardiovascular malformations might be a clinically isolated, or relatively isolated, manifestation of homozygous HOXA1 mutations. Two ABDS probands had relatively mild mental retardation. These individuals blur the clinical distinctions between the BSAS and ABDS HOXA1 variants and broaden the phenotype and genotype of the homozygous HOXA1 mutation clinical spectrum.     

The genetic aetiology of Silver-Russell syndrome

Silver-Russell syndrome (SRS MIM180860) is a disorder characterised by intrauterine and/or postnatal growth restriction and typical facies. However, the clinical picture is extremely diverse due to numerous diagnostic features reflecting a heterogeneous genetic disorder. The mode of inheritance is variable with sporadic cases also being described. Maternal uniparental disomy (mUPD) of chromosome 7 accounts for 10% of SRS cases and many candidate imprinted genes on 7 have been investigated. Chromosome 11 has moved to the forefront as the key chromosome in the aetiology, with reports of methylation defects in the H19 imprinted domain associated with the phenotype in 35-65% of SRS patients. Methylation aberrations have been described in a number of other imprinted growth related disorders such as Beckwith-Wiedmann syndrome. This review discusses these recent developments as well as the previous work on chromosome 7. Other candidate genes/chromosomal regions previously investigated are tabled.     

Knowledge,attitude and behaviour regarding dietary salt intake among medical students in Angola

High salt (sodium chloride) consumption is an important determinant of high blood pressure and cardiovascular risk. According to World Health Organisation (WHO) statistics, over 80% of cardiovascular disease (CVD) deaths take place in low-and middle-income countries, and elevated blood pressure levels were a major cause of these CVD deaths in those countries.1 Lifestyle factors such as unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol have been considered the most important behavioural risk factors for heart disease and stroke.2Among dietary factors, high salt intake has been the most strongly associated with raised blood pressure and increased risk of stroke and CVD.3 Therefore dietary sodium restriction has been recommended as a non-pharmacological approach to blood pressure lowering,4-6 and for the prevention and control of non-communicable diseases at the population level.7,8Cumulative evidence has shown that even a modest reduction in salt intake was associated with blood pressure lowering and therefore with a significant reduction in incidence of cardiovascular events.9-12 Furthermore, data from the most recent systematic review and meta-analyses has shown the benefit of lowering sodium intake in apparently healthy adults and children,13 and in both hypertensive and normotensive individuals, irrespective of gender and ethnic group.9Since hypertension is associated with CVD worldwide, a public health intervention to reduce high blood pressure must target the role of lifestyle, particularly reduced sodium intake.7 Therefore, several countries have initiated strategies to reduce dietary salt intake in the general population by a combination of various procedures such as public education, food labelling, and collaboration with the food industry to reduce the salt content of processed food.14Among sub-Saharan African countries, only Nigeria and South Africa have developed dietary guidelines regarding salt intake.15 Recently, the South African government implemented important specific legislation towards decreasing salt intake in the population by reducing sodium content of processed foods by industries.16 Therefore, the current public health recommendation is that countries should launch national initiatives to reduce the over-consumption of salt as part of non-communicable disease prevention and healthy nutrition policies for limiting salt intake to less than 5 g/day for the general population including children.7 Despite of this guideline, however, high sodium intake remains prevalent around the world, with average daily salt intake varying from 5 to 18 g/day per person.17Although processed foods have been found to be the principal source of excessive dietary salt intake,18 sources of dietary sodium vary largely worldwide and may be influenced by cultural context and dietary habits of the population.19 In sub-Saharan African countries experiencing demographic and epidemiological transition, the rapid rise in prevalence of CVD (chiefly hypertension) has been attributed to lifestyle change, including high dietary sodium intake.20,21 However, consistent data from studies on risk factors are lacking for the majority of these countries.With regard to Angola, available data from a cross-sectional study reported a high prevalence of multiple cardiovascular risk factors, such as hypertension, sedentary lifestyle, electrocardiographic left ventricular hypertrophy,22 and high rate of the metabolic syndrome23 in an apparently healthy middle-aged population of university public employees living in urban and peri-urban areas.Determining the level of sodium intake in the population is crucial to establish intervention strategies and policy on reduction of sodium intake. For medical students in particular, it is very important to assess their awareness regarding dietary salt intake, since they are the future providers of healthcare information for the counselling of people about the need to reduce salt consumption. The aim of this study was to determine salt intake and to assess the knowledge, attitude and behaviour regarding dietary salt among medical students.     

A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.