Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent risk factors?

BACKGROUND: Vitamin D (Vit D) deficiency has been associated with prevalent and incident cardiovascular (CV) disease, suggesting a role for bioregulators of bone and mineral metabolism in CV health. Vitamin D deficiency leads to secondary hyperparathyroidism, and both primary and secondary hyperparathyroidism are associated with CV pathology. Parathyroid hormone (PTH) is an important regulator of calcium homeostasis, and its impact on CV disease risk is of interest. We tested whether elevated PTH is associated with CV disease and whether risk associations depend on Vit D status and renal function. METHODS: Patients in the Intermountain Healthcare system with concurrent PTH and Vit D as 25-hydroxy-vitamin D (25[OH]D) levels were studied (N = 9,369, age 63 ± 16 years, 36% male). Parathyroid hormone levels were defined as low (<15 pg/mL), normal (15-75 pg/mL), or elevated (>75 pg/mL). Prevalence and incidence of hypertension, diabetes, hyperlipidemia, coronary artery disease/myocardial infarction, heart failure, stroke, and peripheral vascular disease were determined by the International Classification of Diseases, Ninth Revision codes documented in electronic medical records at baseline and, for incident events, during an average of 2.0 ± 1.5 years (maximum 7.5 years) of follow-up. RESULTS: Parathyroid hormone elevation at baseline was noted in 26.1% of the study population. Highly significant differential CV prevalence/incidence rates for most CV risk factors, disease diagnoses, and mortality were noted for PTH >75 pg/mL (by 1.25- to 3-fold). Parathyroid hormone correlated only weakly (r = -0.15) with 25(OH)D and moderately with glomerular filtration rate (r = -0.36). 25(OH)D, standard risk factors, and renal dysfunction variably attenuated PTH risk associations, but risk persisted after full multivariable adjustment. CONCLUSIONS: Elevated PTH is associated with a greater prevalence and incidence of CV risk factors and predicts a greater likelihood of prevalent and incident disease, including mortality. Risk persists when adjusted for 25(OH)D, renal function, and standard risk factors. Parathyroid hormone represents an important new CV risk factor that adds complementary and independent predictive value for CV disease and mortality.

EUS diagnosis of a primary pancreatic metastasis of alveolar rhabdomyosarcoma.

CONTEXT: Alveolar rhabdomyosarcoma are rare malignancies. These lesions typically metastasize to the lungs, liver, and bone marrow. Pancreatic metastases from alveolar rhabdomyosarcoma are exceptionally uncommon. CASE REPORT: An 18-year-old man with a history of right orbital alveolar rhabdomyosarcoma, which had been treated with neoadjuvant therapy, surgery and adjuvant chemotherapy developed an episode of pancreatitis. CT at that time demonstrated acute pancreatitis with no mass lesions. Two months later, the patient developed abdominal pain and an MRI documented a 6.4 cm mass in the pancreatic body and tail. EUS guided FNA confirmed the diagnosis of alveolar rhabdomyosarcoma metastatic to the pancreas. CONCLUSION: To our knowledge this is the first reported case of EUS guided FNA diagnosis of alveolar rhabdomyosarcoma metastatic to the pancreas. This is also the only case report of a primary pancreatic metastasis of this type of tumor in a male patient (which occurs less commonly than in females).

Contemporary issues in the prevention and management of postthrombotic syndrome.

OBJECTIVE: To provide an evidence-based review and clinical summary of postthrombotic syndrome (PTS). DATA SOURCES: A literature review was performed via MEDLINE (1950-July 1, 2009) and International Pharmaceutical Abstracts (1970-June 2009) searches using the terms post-thrombotic syndrome, post-phlebitic syndrome, deep vein thrombosis, and compression stockings. DATA SYNTHESIS: PTS is best characterized as a chronic syndrome of clinical signs and symptoms including pain, swelling, parasthesias, and ulceration in the affected limb following deep vein thrombosis (DVT). It occurs in up to half of patients with symptomatic DVT, usually within the first 2 years. Although the pathophysiology of PTS is not well understood, a thrombus may cause venous hypertension and valvular incompetence resulting in edema, tissue hypoxia, and in severe cases, ulceration. Risk factors for PTS include recurrent ipsilateral DVT, obesity, and poor quality of anticoagulant therapy. PTS diagnosis is based on the presence of typical signs and symptoms and may be made using one of several clinical scoring systems. Prevention of PTS should focus on DVT prevention and the use of elastic compression stockings following DVT, while fibrinolysis remains under investigation as an effective method for PTS prevention. The treatment of PTS may include either pharmacologic or mechanical modalities, although none of these regimens has been rigorously tested. Pharmacists have the opportunity to provide more comprehensive antithrombotic management by educating patients and providers on PTS, recommending appropriate preventive therapy, assisting patients in obtaining and adhering to this therapy, and assisting providers with the management of PTS. CONCLUSIONS: Providers should be proactive in preventing PTS, with pharmacists taking an active role in optimal DVT prevention, identifying patients at risk for PTS, and counseling and directing preventive therapies.

Mouse models of hematopoietic engraftment: limitations of transgenic green fluorescent protein strains and a high-performance liquid chromatography approach to analysis of erythroid chimerism.

Transgenic mouse strains ubiquitously expressing green fluorescent protein (GFP) have enabled investigators to develop in vivo transplant models that can detect donor contributions to many different tissues. However, most GFP transgenics lack expression of the reporter in the erythroid lineage. We evaluated expression of GFP in the bone marrow of the OsbY01 transgenic mouse (B6-GFP) in the context of CD71 and TER-119 expression and found that GFP fluorescence is lost prior to the basophilic erythroblast stage of development. However, platelets in B6-GFP mice were found to be uniformly positive for GFP. We therefore used the GFP transgenic model in combination with allelic variants of CD45 and the hemoglobin beta (Hbb) chain to develop a model system that allows all blood lineages to be followed in a mouse model of bone marrow transplantation (BMT). To detect Hbb variant molecules, we developed a new protocol based on high-performance liquid chromatography that is sensitive and precise, allowing rapid and quantitative analysis of erythroid chimerism. Platelet and leukocyte engraftment were detected by flow cytometry. BMT into sublethally irradiated (4 Gy) recipients demonstrated the failure of B6-GFP-derived cells to engraft relative to B6-CD45(a)-derived cells, suggesting that an immune barrier may prevent efficient engraftment of the transgenic cells in a setting of minimal ablation. These results establish limitations in the use of transgenic GFP expression as a donor marker in transplantation models.