Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene

The product of the SLC40A1 gene, ferroportin 1, is a main iron export protein. Pathogenic mutations in ferroportin 1 lead to an autosomal dominant hereditary iron overload syndrome characterized by high serum ferritin concentration, normal transferrin saturation, iron accumulation predominantly in macrophages, and marginal anemia. Iron overload occurs in both the African and the African-American populations, but a possible genetic basis has not been established. We analyzed the ferroportin 1 gene in 19 unrelated patients from southern Africa (N = 15) and the United States (N = 4) presenting with primary iron overload. We found a new c. 744 C-->T (Q248H) mutation in the SLC40A1 gene in 4 of these patients (3 Africans and 1 African-American). Among 22 first degree family members, 10 of whom were Q248H heterozygotes, the mutation was associated with a trend to higher serum ferritin to amino aspartate transferase ratios (means of 14.8 versus 4.3 microg/U; P = 0.1) and lower hemoglobin concentrations (means of 11.8 versus 13.2 g/dL; P = 0.1). The ratio corrects serum ferritin concentration for alcohol-induced hepatocellular damage. We also found heterozygosity for the Q248H mutation in 7 of 51 (14%) southern African community control participants selected because they had a serum ferritin concentration below 400 microg/L and in 5 of 100 (5%) anonymous African-Americans, but we did not find the change in 300 Caucasians with normal iron status and 25 Caucasians with non-HFE iron overload. The hemoglobin concentration was significantly lower in the African community controls with the Q248H mutation than in those without it. We conclude that the Q248H mutation is a common polymorphism in the ferroportin 1 gene in African populations that may be associated with mild anemia and a tendency to iron loading.     

Immunosuppression among HIV‐1‐positive patients attending for care: experience from two large HIV centres in the United Kingdom

Objectives

The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4<200 cells/μL) among HIV‐infected patients attending two large inner London treatment centres.

Methods

Patients attending for care who had a CD4 count <200 cells/μL during a 6‐month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count >200 cells/μL at any time under follow‐up which had decreased (group A) or never had a CD4 count >200 cells/μL (group B; late presenters).

Results

Of 4589 patients, 10.2% (467) had at least one CD4 count <200 cells/μL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to <200 cells/μL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS‐defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B.

Conclusion

The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care.     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Injection drug use among street-involved youth in a Canadian setting

Background  

Street-involved youth contend with an array of health and social challenges, including elevated rates of blood-borne infections and mortality. In addition, there has been growing concern regarding high-risk drug use among street-involved youth, in particular injection drug use. We undertook this study to examine the prevalence of injection drug use and associated risks among street-involved youth in Vancouver, Canada.     

Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting

Background  

There has emerged growing recognition of the link between housing and health. Since Vancouver, Canada has had increasing concerns with homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games, we evaluated hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing.     

Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is effective in advanced multiple myeloma

Fifty-three patients with multiple myeloma (MM) underwent an allogeneic stem cell transplant (HSCT) from their HLA identical siblings using a reduced-intensity conditioning consisting of thioteopa 5 mg/kg, fludarabine 90 mg/m(2), and melphalan 80 mg/m(2). Their median age was 52 years (range 38 - 68) and the interval from diagnosis 12 months. Forty-three patients (82%) had advanced disease and 33 had previously been treated with high-dose therapy with one (N = 21), or more (N = 12) autologus transplants. Ten (18%) had their allograft programmed after induction chemotherapy. The majority (N = 44) received peripheral blood as stem cell source. Acute graft-versus-host disease (GVHD) grade II - IV developed in 45%, but grade III - IV in only 5%. Cumulative incidence of chronic GVHD was 64%. Sixty-two per cent were in complete remission (CR) following transplantation. Transplant-related mortality was 13%. Relapse incidence was 32%. With a median follow-up of 22 months, 3-year overall survival is 45% and progression free survival (PFS) 37%. The thiotepa, fludarabine, and melphalan conditioning regimen can produce remissions in the majority of MM patients with a limited transplant mortality rate. When used as first line treatment the results of transplantation appear even more encouraging.