A number of previous studies have reported a potential risk of malignancy, particularly hematological malignancy, developing in patients receiving a metal-on-metal (MoM) hip replacement. We report a ...case of malignant lymphoma that arose in a patient who had an MoM hip arthroplasty complicated by development of a pseudotumour. The tumour was a B cell follicular lymphoma that involved lymph nodes and bone. Metal ions are known to have a genotoxic effect on lymphoid cells. Although epidemiological studies have not established that there is an increased risk of lymphoma associated with MoM implants, only a relatively short time period has elapsed since re-introduction of this type of implant and long-term follow-up of patients with MoM implants is indicated.
Abstract
Although statistically unlikely, early-onset breast cancer tends to be more aggressive and leads to greater mortality than breast cancer among women of screening age. Young African American ...women are disproportionately impacted by early-onset breast cancer compared to women of other races. Given the racial disparities and because young women are typically not the primary audience for breast cancer educational messaging, there is a need to identify recommendations for age-appropriate breast cancer education for African American women below mammogram eligibility. Through N = 30 key informant interviews with young African American breast cancer survivors, family members of young survivors, community organization leaders and healthcare providers, we identified breast cancer educational message content and communication channels relevant for these women. Participants recommended that message content should emphasize the need to address family cancer history and self-advocacy in healthcare encounters in addition to concerns about loss of womanhood, financial costs and opportunity costs associated with preventive healthcare visits. Breast cancer messages for this audience should consider the influences of earlier life stage, culture and race. Recommended communication channels highlighted use of social media and videos. Findings will inform future age-appropriate educational messaging aimed at eliminating early-onset breast cancer disparities disproportionately impacting young African American women.
Summary
Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic
RAS
mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals ...were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found.
Purpose
CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic
RAS
mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia.
Methods
Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed.
Results
Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported.
Conclusion
An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.
The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ...ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel.
The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2).
Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis.
Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.
Urban estuaries around the world are experiencing contamination from diffuse and point sources, which increases risks to public health. To mitigate and manage risks posed by elevated levels of ...contamination in urban waterways, it is critical to identify the primary water sources of contamination within catchments. Source tracking using microbial community fingerprints is one tool that can be used to identify sources. However, results derived from this approach have not yet been evaluated using independent datasets. As such, the key objectives of this investigation were: (1) to identify the major sources of water responsible for bacterial loadings within an urban estuary using microbial source tracking (MST) using microbial communities; and (2) to evaluate this method using a 3-dimensional hydrodynamic model. The Yarra River estuary, which flows through the city of Melbourne in South-East Australia was the focus of this study. We found that the water sources contributing to the bacterial community in the Yarra River estuary varied temporally depending on the estuary's hydrodynamic conditions. The water source apportionment determined using microbial community MST correlated to those determined using a 3-dimensional hydrodynamic model of the transport and mixing of a tracer in the estuary. While there were some discrepancies between the two methods, this investigation demonstrated that MST using bacterial community fingerprints can identify the primary water sources of microorganisms in an estuarine environment. As such, with further optimization and improvements, microbial community MST has the potential to become a powerful tool that could be practically applied in the mitigation of contaminated aquatic systems.
Display omitted
•A novel source tracking method using microbial community fingerprints is proposed.•Sources of water contamination to an estuary were estimated using SourceTracker.•This new method was independently checked against a 3D hydrodynamic model.
Aims/hypothesis
Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, ...we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
Methods
A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.
Results
A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.
Conclusions/interpretation
Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.
BACKGROUND Adverse pregnancy outcomes have been associated with maternal celiac disease (CD). In this study, we investigate the effect of treated and untreated maternal CD on infant birthweight and ...preterm birth. METHODS A population-based cohort study consisted of all singleton live births in Denmark between 1 January 1979 and 31 December 2004 was used. A total of 1 504 342 babies were born to 836 241 mothers during the study period. Of those, 1105 babies were born to women with diagnosed CD and 346 were born to women with undiagnosed CD. Women with diagnosed CD were considered as treated with a gluten free diet while women with undiagnosed CD were considered as untreated. The outcome measures were: birthweight, small for gestational age (SGA: birthweight <10th centile), very small for gestational age (VSGA: birthweight <5th centile) and preterm birth. We compared these measures in treated and untreated women with those of a reference group (no history of CD). RESULTS Women with untreated CD delivered smaller babies difference = −98 g (95% CI: −130, −67), with a higher risk of SGA infants OR = 1.31 (95% CI: 1.06, 1.63), VSGA infants OR = 1.54 (95% CI: 1.17, 2.03) and preterm birth OR = 1.33 (95% CI: 1.02, 1.72) compared with women without CD. Women with treated CD had no increased risk of reduced mean birthweight, risk of delivering SGA and VSGA infants or preterm birth compared with women without CD. CONCLUSION Untreated maternal CD increases the risk of reduced birthweight, the risk of delivering SGA and VSGA infants and preterm birth. Diagnosis and presumed treatment of maternal CD with a gluten-free diet appeared to result in a birthweight and preterm birth rate similar to those in women without CD.
Background:
Altered intestinal dendritic cell (DC) function underlies dysregulated T‐cell responses to bacteria in Crohn's disease (CD) but it is unclear whether composition of the intestinal ...microbiota impacts local DC function. We assessed the relationship between DC function with disease activity and intestinal microbiota in patients with CD.
Methods:
Surface expression of Toll‐like receptor (TLR)‐2, TLR‐4, and spontaneous intracellular interleukin (IL)‐10, IL‐12p40, IL‐6 production by freshly isolated DC were analyzed by multicolor flow cytometry of cells extracted from rectal tissue of 10 controls and 28 CD patients. Myeloid DC were identified as CD11c+HLA‐DR+lin‐/dim cells (lin = anti‐CD3, CD14, CD16, CD19, CD34). Intestinal microbiota were analyzed by fluorescent in situ hybridization of fecal samples with oligonucleotide probes targeting 16S rRNA of bifidobacteria, bacteroides‐prevotella, C. coccoides‐E. rectale, and Faecalibacterium prausnitzii.
Results:
DC from CD produced higher amounts of IL‐12p40 and IL‐6 than control DC. IL‐6+ DC were associated with the CD Activity Index (r = 0.425; P = 0.024) and serum C‐reactive protein (CRP) (r = 0.643; P = 0.004). DC expression of TLR‐4 correlated with disease activity. IL‐12p40+ DC correlated with ratio of bacteroides: bifidobacteria (r = 0.535, P = 0.003). IL‐10+ DC correlated with bifidobacteria, and IL‐6+ DC correlated negatively with F. prausnitzii (r = −0.50; P = 0.008). The amount of TLR‐4 on DC correlated negatively with the concentration of F. prausnitzii.
Conclusions:
IL‐6 production by intestinal DC is increased in CD and correlates with disease activity and CRP. Bacterially driven local IL‐6 production by intestinal DC may overcome regulatory activity, resulting in unopposed effector function and tissue damage. Intestinal DC function may be influenced by the composition of the commensal microbiota. (Inflamm Bowel Dis 2011;)
The brain has been known to be a sensitive target organ for the permanent organisational effects of gonadal steroids for close to 50 years. Recent advances have revealed a variety of unexpected ...cellular mechanisms by which steroids impact on the synaptic profile of hypothalamic nuclei critical to the control of reproduction. This review focuses on three in particular: 1) prostaglandins in the masculinisation of the preoptic area and control of male sexual behaviour; 2) GABA in the arcuate nucleus and potential control of the anterior pituitary; and 3) non‐genomic activation of phosphotydolinositol 3 (PI3) kinase and glutamate in the ventromedial nucleus, which is relevant to the control of female reproductive behaviour. The importance of cell‐to‐cell communication, be it between neurones or between neurones and astrocytes, is highlighted as an essential principle for expanding the impact of steroids beyond those cells that express nuclear receptors.
PDF
