Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a variety of mechanisms including increased phosphorus and fibroblast growth factor 23 (FGF23), and decreased calcium and 1,25-dihydroxy vitamin D levels. Patients present with various bone disorders, cardiovascular disease, and typical laboratory abnormalities. Medical treatment consists of controlling hyperphosphatemia, vitamin D/analog and calcium administration, and calcimimetic agents. Improved medical therapies have led to a decrease in the use of parathyroidectomy (PTX). The surgical indications include parathyroid hormone (PTH) levels >800 pg/ml associated with hypercalcemia and/or hyperphosphatemia despite medical therapy. Other indications include calciphylaxis, fractures, bone pain or pruritis. Transplant recipients often show decreased PTH, calcium and phosphorus levels, but some will have persistent HPT. Evidence suggests that PTX may cause deterioration in renal graft function in the short-term calling into the question the indications for PTX in these patients. Pre-operative imaging is only occasionally helpful except in re-operative PTX. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages and disadvantages which are discussed. Intraoperative PTH monitoring has a high positive predictive value of cure but a poor negative predictive value and therefore is of limited utility. Hypocalcemia is the most common complication requiring aggressive calcium administration. Benefits of surgery may include improved survival, bone mineral density and alleviation of symptoms.

Importance: Dynamic computed tomography (CT) is emerging as a first-line alternative to sestamibi scintigraphy for preoperative localization of parathyroid lesions. In recent years, there has been increased concern over the impact of radiation exposure from medical imaging, as well as on the cost of diagnostic medical procedures. An ideal diagnostic procedure would be cost effective while minimizing hazardous exposures and complication rates.Objective: To compare the radiation dose and financial cost of dynamic CT with sestamibi scintigraphy. Main Outcomes and Measures:The 2 primary study outcomes were radiation exposure measured in millisieverts (mSv) and medical charges for the respective diagnostic procedures. The study was conducted with the hypothesis that dynamic parathyroid CT would have slightly greater radiation exposure with similar cost to sestamibi scintigraphy.Results: Dynamic parathyroid CT and sestamibi scintigraphy delivered mean radiation doses of 5.56 and 3.33 mSv, respectively (P Ͻ .05). Charges totaled $1296 for thin-cut dynamic parathyroid CT and a mean of $1112 for sestamibi scintigraphy, depending on the type and amount of radiotracer injected. Although multiphase CT scanning took less than 5 minutes, sestamibi scintigraphy lasted a mean time of 306 minutes. A total of 62 of 119 patients (52%) in the CT group have undergone operative treatment to date, whereas all patients in the sestamibi arm underwent operative treatment of their hyperparathyroidism. Of the patients who underwent a surgical procedure, CT correctly identified the side of the parathyroid adenoma in 54 of 62 patients (87%), while sestamibi scintigraphy only correctly lateralized 90 of 122 adenomas (74%) as confirmed by exploratory surgery, intraoperative parathyroid hormone levels, and pathologic features. A dynamic parathyroid CT correctly predicted multiglandular disease in 1 of 7 patients (14%), while sestamibi scintigraphy correctly predicted multiglandular disease in 8 of 23 patients (35%). Conclusions and Relevance:In patients who underwent directed parathyroid surgery, dynamic CT is comparable to sestamibi scintigraphy in patients with hyperparathyroidism. Although CT delivers a higher dose of radiation, the average background radiation exposure in the United States is 3 mSv/y, and added exposures of less than 15 mSv are considered low risk for carcinogenesis. Overall, dynamic parathyroid CT is a safe, cost-effective alternative to sestamibi scintigraphy.

Maternal antibody is the major form of protection from disease in early life when the neonatal immune system is still immature; however, the presence of maternal antibody also interferes with active immunization, placing infants at risk for severe bacterial and viral infection. We tested the ability of intramuscular and gene gun immunization with DNA expressing influenza virus hemagglutinin (HA) and nucleoprotein (NP) to raise protective humoral and cellular responses in the presence or absence of maternal antibody. Neonatal mice born to influenza virus-immune mothers raised full antibody responses to NP but failed to generate antibody responses to HA. In contrast, the presence of maternal antibody did not affect the generation of long-lived CD8 ؉ T-cell responses to both HA and NP. Thus, maternal antibody did not affect cell-mediated responses but did affect humoral responses, with the ability to limit the antibody response correlating with whether the DNA-expressed immunogen was localized in the plasma membrane or within the cell.Neonates are deficient in several components of inflammatory, innate, and specific immune responses. The presence of high-titer maternal antibody in newborns is the major form of protection from disease in early life. Maternal immunoglobulin G (IgG) crosses the placenta from mother to fetus during development (12) and typically exceeds titers of the same antibody in the mother. This passive antibody slowly declines over the first year of life, a period during which the infant's immune system matures, becomes more experienced, and develops its own repertoire of protective memory immune responses. However, maternal antibody can also interfere with active immunization of the offspring (1). Immunization protocols are often delayed several months and/or require multiple booster immunizations to achieve the desired protective immune response. Thus, a window of time exists when maternal antibody levels are too low to reliably protect an infant from infectious disease but are high enough to prevent responses to vaccines.DNA vaccination is an attractive method for immunization in the presence of maternal antibody. Maternal antibody is thought to interfere with traditional vaccine efficacy by reducing the amount of antigen available for processing and presentation by antigen-presenting cells. The ability of DNA vaccines to directly transfect cells bypasses this problem. The maternal antibody will not inhibit the DNA vaccine itself because antigen is not available until de novo synthesis occurs. Both DNA and subsequent antigen expression persists for several weeks (4, 6). Thus, DNA-raised immune responses could occur as maternal antibody titers wane. Some groups have reported success following neonatal DNA immunization in the presence of maternal antibody (14), while others have failed (11,15,21,25).We have previously shown that intramuscular (i.m.) and gene gun (g.g.) immunization of mice as neonates or adults with an influenza hemagglutinin (HA)-expressing DNA generates long-lasting protectiv...

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