Malignant breast cancer in children: a review of 75 patients

OBJECTIVE: To determine incidence trends and outcomes for pediatric patients with malignant breast disease. METHODS: The Surveillance, Epidemiology, and End Results registry was examined for all females 19 years of age and younger diagnosed with a malignant breast tumor between 1973 and 2004. RESULTS: A total of 75 patients with malignant breast tumors were identified. Overall, 14.5% of patients had in situ tumors, and 85.5% had invasive disease. Tumors were classified as being either carcinomas (n = 41, 54.7%) or sarcomas (n = 34, 45.3%). The majority of sarcomatous lesions were phyllodes tumors (n = 29, 85.5%), whereas most carcinomas were of a ductal etiology (n = 19, 46.3%). The age-adjusted incidence of all malignant pediatric breast tumors in 2003 was 0.08 cases per 100,000 people (0.03 carcinoma and 0.06 sarcoma cases per 100,000 people). In the carcinoma group, regionally advanced disease was present in 11 patients (26.8%), whereas only 3 patients (7.3%) presented with metastatic disease. All patients with sarcomatous tumors presented with localized disease. Adjuvant radiation therapy was administered in only 9.8% of carcinomas and 8.8% of sarcomas, and 85.4% of carcinoma patients and 97.1% of sarcoma patients underwent surgical resection for their primary disease. Subgroup analysis revealed 5- and 10-year survival rates of 89.6% for patients with sarcomatous tumors and 63.1% and 54.3% for carcinomas. CONCLUSIONS: Malignant pediatric breast malignancies remain relatively rare. The two most common histologies of breast neoplasms in children are malignant carcinomas followed by sarcomas. Although uncommon, malignant disease must be considered in the differential diagnosis of the pediatric patient with a breast mass.     

Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes.     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

Association of serum levels of aggrecan ARGS,NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients

ObjectivesProteolytic degradation of aggrecan is a hallmark of the pathology of osteoarthritis. The aim of this study was to develop enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of specific aggrecan fragments generated by aggrecanases-mediated cleavage. We investigated the relationships between these two aggrecan degradations fragments and urinary CTX-II levels.MethodsThe competitive ELISAs employ a polyclonal antibody raised against the aggrecan fragments containing two neoepitopes NITEGE³⁷³ and ³⁷⁴ARGSVI. We measured serum levels of ARGSV and NITEGE in 125 women with knee osteoarthritis (mean ± SD age of 53.6 ± 7.6 years, mean ± SD disease duration of 3.6 ± 3.8 years), and 57 women age-matched controls.ResultsAggrecan neoepitopes assays showed an intra- and inter-assay imprecision (CV) lower than 20% for both tests and good linearity. Median serum ARGSVI (by 18%; P = 0.002), and NITEGE (36.4%; P < 0.001) levels were significantly decreased in patients with knee osteoarthritis compared with controls. Minimal joint space width was negatively correlated with ARGSVI (r = –0.368, P = 0.04) and NITEGE (r = –0.274, P = 0.038) in knee osteoarthritis patients. Median urinary CTX-II levels were significantly increased by 39.5% (P = 0.001) in knee OA patients compared with controls.ConclusionMarkers of degradation aggrecan were analyzed for the first time in an African osteoarthritis population. These markers can be used to monitor aggrecanase activity in human joint disease. Their combination with CTX-II can improve clinical investigation of patients with osteoarthritis patients.     

A total ban on alcohol advertising: presenting the public health case

Evidence from burden of disease and economic costing studies amply indicate that the public health burden from hazardous and harmful use of alcohol in South Africa warrants drastic action. Evidence that banning alcohol advertising is likely to be an effective intervention is reflected in WHO strategy documents on non-communicable diseases and harmful use of alcohol. Studies on young people furthermore support arguments refuting the claim that advertising only influences brand choice. Given the weakness of relying on industry self-regulation, the government is considering legislation to ban alcohol advertising, resulting in heated debate. Tobacco control and studies investigating the effect of alcohol advertising bans on consumption and alcohol-related deaths point to the effectiveness of such action - ideally supplemented by other policy interventions. Arguments against an advertising ban include possible communication sector job losses, but these are likely to have been exaggerated. Banning alcohol advertising will necessitate greater scrutiny of digital media, satellite television and merchandising to reduce the likelihood of subverting the ban.     

Systematic review and meta‐analysis of the efficacy of epidermal grafting for wound healing

Autologous skin grafting is an important method for wound coverage; however, it is an invasive procedure and can cause donor site morbidity. Epidermal grafting (EG) enables epidermal transfer to wounds with minimal donor site morbidity. However, data to date have been heterogeneous. This study aims to synthesise the current evidence on EG for wound healing to establish the efficacy of this surgical technique. A comprehensive search in the MEDLINE, EMBASE and CENTRAL databases was conducted. The endpoints assessed were proportion of wounds healed and mean wound‐healing time. This systematic review was conducted and reported according to the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We identified 1568 articles, of which seven articles were included in this review – a total of 209 wounds in 190 patients. The mean wound duration was 17·06 weeks (95% CI 8·57–25·55). Of these, 71·5% (95% CI 56·7–84·2) of the wounds achieved complete healing. Mean time for complete wound healing was 5·53 weeks (95% CI 3·18–7·88). The mean donor site healing time was 7·48 days (95% CI 4·83–10·13), with no reported donor site morbidity. The current data are small and lack level 1 evidence.     

Effect of apelin on glomerular hemodynamic function in the rat kidney

Apelin is a vasoactive peptide identified as the endogenous ligand of an orphan G protein-coupled receptor called APJ. Apelin and its receptor have been found in the brain and the cardiovascular system. Here we show that the apelin receptor mRNA is highly expressed in the glomeruli while its level of expression is lower in all nephron segments including collecting ducts that express vasopressin V2 receptors. Intravenous injection of apelin 17 into lactating rats induced a significant diuresis. Apelin receptor mRNA was also found in endothelial and vascular smooth muscle cells of glomerular arterioles. Apelin administration caused vasorelaxation of angiotensin II-preconstricted efferent and afferent arterioles as shown by an increase in their diameter. Activation of endothelial apelin receptors caused release of nitric oxide which inhibited angiotensin II-induced rise in intracellular calcium. In addition, it appears that apelin had a direct receptor-mediated vasoconstrictive effect on vascular smooth muscle. These results show that apelin has complex effects on the pre- and post glomerular microvasculature regulating renal hemodynamics. Its role on tubular function (if any) remains to be determined.