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Sample records for association determines parathyroid

  1. Association between atypical parathyroid adenoma and neurofibromatosis.

    PubMed

    Favere, Aline Mesquita Ferreira de; Tsukumo, Daniela Miti; Matos, Patrícia Sabino de; Santos, Sérgio Luiz Marques dos; Lalli, Cristina Alba

    2015-10-01

    Primary hyperparathyroidism is a disease characterized by excessive production of parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases. An atypical parathyroid adenoma, with some histopathological features of parathyroid carcinoma, may be found in some of the cases, although it may not fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an autosomal dominant systemic disease that may be associated with hyperparathyroidism. We report here the rare combination of a patient with NF1 and clinical manifestations of hyperparathyroidism due to an atypical parathyroid adenoma. PMID:26421674

  2. CDC73 Intragenic Deletion in Familial Primary Hyperparathyroidism Associated With Parathyroid Carcinoma

    PubMed Central

    Korpi-Hyövälti, Eeva; Cranston, Treena; Ryhänen, Eeva; Arola, Johanna; Aittomäki, Kristiina; Sane, Timo; Thakker, Rajesh V.

    2014-01-01

    Context: CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations. Objective: To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations. Patients and Methods: Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA. Results: A previously unreported deletion of CDC73 involving exons 1–10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts. Conclusion: A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder. PMID:24823466

  3. Significant association between parathyroid hormone and uric acid level in men

    PubMed Central

    Chin, Kok-Yong; Ima Nirwana, Soelaiman; Wan Ngah, Wan Zurinah

    2015-01-01

    Background Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men. Methods A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis. Results Increased serum PTH level was significantly associated with increased serum uric acid level (β=0.165; P=0.001). Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017–1.075; P=0.002). All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels. Conclusion There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study. PMID:26346636

  4. Parathyroid Adenoma Associated with Granulomatous Inflammation: A Curious Cause of Hypercalcaemia

    PubMed Central

    Singh, Hena Paul; Sood, Neena; Puri, Harpreet

    2016-01-01

    Primary Hyperparathyroidism (PHPT) due to solitary parathyroid adenoma followed by parathyroid hyperplasia and carcinoma are the most frequent cause of hypercalcaemia. The most common granulomatous disorders causing hypercalcaemia are sarcoidosis and tuberculosis. We have reported a case where unexplained granulomas were seen along with parathyroid adenoma. PMID:27190821

  5. Association of a wide invasive malignant thymoma with myastenia gravis and primary hyperparathyroidism due to parathyroid adenoma: case report and review of the literature.

    PubMed

    Triggiani, Vincenzo; Guastamacchia, Edoardo; Lolli, Ivan; Troccoli, Giuseppe; Resta, Francesco; Sabbà, Carlo; Ruggieri, Nadia; Tafaro, Emilio

    2006-01-01

    There are few cases described in the world literature reporting an association of thymoma (with myasthenia gravis or not) with hyperparathyroidism. In these cases the hyperparathyroidism was due to the presence of an adenoma or hyperplasic parathyroid tissue either in the cervical region or in an ectopic intrathymic location.(12345) In other cases the syndrome of hypercalcemia was due to the secretion of parathyroid-related protein (PTHRP) (6) or parathyroid hormone (PTH) (7) by the thymoma itself. We report the first case, at the best of our knowledge, of a wide invasive malignant thymoma (type B3), associated with myasthenia gravis and hyperparathyroidism caused by parathyroid adenoma. PMID:16873103

  6. Parathyroid cancer

    MedlinePlus

    ... the thyroid gland, which is located at the base of the neck. Parathyroid cancer is a very rare type of cancer. Men and women are equally affected. It usually occurs in people older than 30. The cause of parathyroid cancer ...

  7. Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions.

    PubMed

    Liu, Zhijie; Farley, Alison; Chen, Lizhen; Kirby, Beth J; Kovacs, Christopher S; Blackburn, C Clare; Manley, Nancy R

    2010-01-01

    In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2⁻/⁻ mutants. However, the developmental ontogeny and cellular identity of these "thymic" PTH-expressing cells is unknown. We found that the lethality of aparathyroid Gcm2⁻/⁻ mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2⁻/⁻ mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant "thymic

  8. Primary hyperparathyroidism due to an intrathyroidal parathyroid adenoma associated with chronic lymphocytic thyroiditis

    PubMed Central

    Cating-Cabral, Monica Therese; Cabungcal, Arsenio Claro; Villafuerte, Cesar Vincent; Añel-Quimpo, Joselynna

    2012-01-01

    This is a case of a 44-year-old woman with an anterior neck mass and hypothyroidism who presented with an incidental finding of an elevated serum calcium level and was found to have primary hyperparathyroidism and osteoporosis. During surgical exploration no parathyroid adenoma was found, although a nodule was palpated within the right thyroid lobe. Examination of the excised right thyroid lobe revealed an intrathyroidal parathyroid adenoma and chronic lymphocytic thyroiditis. After surgery, she did not develop severe hypocalcaemia and this was attributed to preoperative treatment with pamidronate. In the months following surgery, parathyroid hormone remained undetectable. PMID:22684835

  9. Parathyroid carcinoma associated with chronic renal failure and previous radiotherapy to the neck.

    PubMed Central

    Ireland, J P; Fleming, S J; Levison, D A; Cattell, W R; Baker, L R

    1985-01-01

    Carcinoma of the larynx was treated by irradiation followed by laryngectomy in a man who had been receiving regular haemodialysis for two years. At least one, and probably two, parathyroid glands were removed at this time, and the remaining two were removed three years later for tertiary hyperparathyroidism. A portion of one gland was implanted into the forearm. The forearm implant was resected the following year for recurrent hypercalcaemia. Six years later, again with recurrent hypercalcaemia, he died of bronchopneumonia. Metastatic parathyroid carcinoma was found in the apex of the left lung. The source of this parathyroid tissue and the possible role of irradiation in the pathogenesis of parathyroid cancer in this patient were investigated. Images PMID:4056066

  10. Association between Parathyroid Hormone Levels and Inflammatory Markers among US Adults

    PubMed Central

    Cheng, Shih-Ping; Liu, Chien-Liang; Liu, Tsang-Pai; Hsu, Yi-Chiung; Lee, Jie-Jen

    2014-01-01

    Background and Aims. High levels of parathyroid hormone (PTH) appear to be associated with an increased mortality. Previous studies concerning the relationship of inflammatory markers with hyperparathyroidism have yielded inconsistent results. This study investigated whether serum PTH concentrations were independently associated with several inflammatory markers among the US adults. Materials and Methods. Using data from the National Health and Nutrition Examination Survey, we examined the relation between serum PTH and C-reactive protein (CRP), red cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR) levels with weighted linear regression. Additionally, we examined the relation with increased modified Glasgow Prognostic Score (mGPS) by using weighted logistic regression. Results. CRP, RDW, and PLR values increased with increasing serum PTH concentration. After extensively adjusting for covariates, CRP and RDW increased linearly and across PTH categories (all P < 0.001), while PLR marginally increased (P = 0.190 and P = 0.095 using PTH as a categorical and continuous variable, resp.). The odds ratio of increased mGPS was 1.11 and 1.31 across PTH categories and with increasing PTH levels continuously. Conclusion. These nationally representative data indicate that serum PTH levels are independently associated with several inflammatory markers in the US population. The casual relationship between PTH levels and inflammation remains to be elucidated. PMID:24782595

  11. Serum parathyroid hormone (PTH) in pregnant women determined by an immunoradiometric assay for intact PTH

    SciTech Connect

    Davis, O.K.; Hawkins, D.S.; Rubin, L.P.; Posillico, J.T.; Brown, E.M.; Schiff, I.

    1988-10-01

    Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

  12. Parathyroid cancer

    PubMed Central

    McClenaghan, Fiona

    2015-01-01

    Parathyroid carcinoma is an exceedingly rare endocrine malignancy first described in 1933. It accounts for between 0.5% and 5% of all cases of primary hyperparathyroidism. Parathyroid carcinoma is unusual among endocrine malignancies, being more hormonally active than its benign counterpart. Parathyroid carcinoma poses a diagnostic challenge both clinically and histologically due to the lack of features which can definitively distinguish malignant from benign disease early in its clinical course. Here, we describe the clinical features of the disease, and present the current opinion on optimal management. Further, we analyse the most recent histological advances made to aid in the diagnosis and management of this rare, but potentially devastating, disease. PMID:26312219

  13. Parathyroid carcinoma.

    PubMed

    Butt, Waqas Tariq; Azim, Asad; Abbas, Ansab; Gauhar, Tooba Mahmud; Afzal, Ameer; Azim, Khawaja Muhammad

    2012-09-01

    Parathyroid carcinoma is a rare endocrine malignancy accounting for less than 1% of all cases of hyperparathyroidism. We present a case of a middle-aged woman who was undiagnosed for 3 years before presenting with renal stones and advanced musculoskeletal disease. Investigations revealed primary hyperparathyroidism. Focused cervical exploration and left inferior parathyroidectomy was carried out based on the pre-operative localization studies. Parathyroid carcinoma was diagnosed on histopathology postoperatively. Subsequent en bloc resection was not performed and the patient is being monitored with serial parathyroid hormone levels which have not shown any increase in 6 months of follow-up. Only two previous cases of parathyroid carcinoma have been reported from Pakistan. PMID:22980615

  14. Parathyroid adenoma

    MedlinePlus

    ... in the neck help control calcium use and removal by the body. They do this by producing parathyroid hormone, or PTH. PTH helps control calcium, phosphorus, and vitamin D levels in the blood and ...

  15. A case of congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma mimicking a carotid body tumor.

    PubMed

    Malm, Ian-James; Olcott, Clara M; Chan, Jason Y K; Loyo, Myriam; Kim, Young J

    2013-01-01

    Ectopic parathyroid adenomas can be encountered during four gland explorations, but nearly 80% of adenomas are localized with ultrasound and sestamibi imaging. Ectopic adenomas are thought to arise from abnormal migration during development. As a cervical congenital anomaly, common carotid artery agenesis is an extremely rare anomaly characterized by separate origins of the internal and external carotid arteries directly from the aortic arch. Here we present a case of a 75 year old man with primary hyperparathyroidism who was found to have congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma within the parapharyngeal space, which mimicked a carotid body tumor based on location and imaging. The successful identification and resection of the ectopic parathyroid adenoma presented here demonstrate the importance of preoperative imaging studies to allow appropriate operative planning as well as the utility of intraoperative parathyroid hormone assay in predicting cure during surgery. PMID:23993711

  16. Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

    PubMed

    Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

    2012-06-01

    Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. PMID:22407786

  17. 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study

    PubMed Central

    Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Kim, Hee Nam; Shin, Min-Ho

    2016-01-01

    In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30–7.63], Q2: 7.25% [7.09–7.40], Q3: 7.17% [7.02–7.32], Q4: 7.19% [7.02–7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19–7.51], Q2: 7.34% [7.19–7.50], Q3: 7.28% [7.13–7.43], Q4: 7.09% [6.94–7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID:27362844

  18. 25-Hydroxyvitamin D and Parathyroid Hormone Levels Are Independently Associated with the Hemoglobin A1c Level of Korean Type 2 Diabetic Patients: The Dong-Gu Study.

    PubMed

    Choi, Seong-Woo; Kweon, Sun-Seog; Lee, Young-Hoon; Ryu, So-Yeon; Choi, Jin-Su; Rhee, Jung-Ae; Nam, Hae-Sung; Jeong, Seul-Ki; Park, Kyeong-Soo; Kim, Hee Nam; Shin, Min-Ho

    2016-01-01

    In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30-7.63], Q2: 7.25% [7.09-7.40], Q3: 7.17% [7.02-7.32], Q4: 7.19% [7.02-7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19-7.51], Q2: 7.34% [7.19-7.50], Q3: 7.28% [7.13-7.43], Q4: 7.09% [6.94-7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels. PMID:27362844

  19. [Parathyroid carcinoma].

    PubMed

    Poissonnet, Gilles; Castillo, Laurent; Bozec, Alexandre; Peyrottes, Isabelle; Ettore, Francette; Santini, José; Demard, François; Dassonville, Olivier

    2006-03-01

    Parathyroid carcinoma is a rare disease accounting for 1 to 5% of parathyroid neoplasms. This malignant tumour must be suspected when a severe primary hyperparathyroidism occurs with high hypercalcemia and elevated parathormon levels. At this time, a cervical mass is often palpable. Both head and neck ultrasonography and 99mTc-sestamibi scintigraphy are the best preoperative imaging tests to suspect and localize the tumour. Surgical approach with simultaneous tumorectomy and hemithyroidectomy, completed by selective neck dissection (level VI) is the treatment of choice. An elective lateral neck dissection should be performed if necessary. Tumour control should be monitored by regular measurement of calcium and parathormon levels. Local recurrence or metastasis risk is 30 to 70% and the 5 year overall survival about 50 to 80%. In case of recurrence, aggressive surgical management should be applied and adjuvant radiation therapy may be discussed. PMID:16567315

  20. Vitamin D status among Thai school children and the association with 1,25-Dihydroxyvitamin D and parathyroid hormone levels.

    PubMed

    Houghton, Lisa A; Gray, Andrew R; Harper, Michelle J; Winichagoon, Pattanee; Pongcharoen, Tippawan; Gowachirapant, Sueppong; Gibson, Rosalind S

    2014-01-01

    In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6-14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations (geometric mean ± geometric SD) were 72.7±1.2 nmol/L, 199.1±1.3 pmol/L and 35.0±1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P = 0.001); no decline was seen in male participants with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)2D, height and sex were associated with 1,25(OH)2D with females exhibiting statistically significantly higher serum 1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption. PMID:25111832

  1. Parathyroid hormone - Secretion and metabolism in vivo.

    NASA Technical Reports Server (NTRS)

    Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

    1971-01-01

    Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

  2. Minimally invasive parathyroid surgery

    PubMed Central

    Noureldine, Salem I.; Gooi, Zhen

    2015-01-01

    Traditionally, bilateral cervical exploration for localization of all four parathyroid glands and removal of any that are grossly enlarged has been the standard surgical treatment for primary hyperparathyroidism (PHPT). With the advances in preoperative localization studies and greater public demand for less invasive procedures, novel targeted, minimally invasive techniques to the parathyroid glands have been described and practiced over the past 2 decades. Minimally invasive parathyroidectomy (MIP) can be done either through the standard Kocher incision, a smaller midline incision, with video assistance (purely endoscopic and video-assisted techniques), or through an ectopically placed, extracervical, incision. In current practice, once PHPT is diagnosed, preoperative evaluation using high-resolution radiographic imaging to localize the offending parathyroid gland is essential if MIP is to be considered. The imaging study results suggest where the surgeon should begin the focused procedure and serve as a road map to allow tailoring of an efficient, imaging-guided dissection while eliminating the unnecessary dissection of multiple glands or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may be measured during the procedure, or a gamma probe used during radioguided parathyroidectomy, to ascertain that the correct gland has been excised and that no other hyperfunctional tissue is present. MIP has many advantages over the traditional bilateral, four-gland exploration. MIP can be performed using local anesthesia, requires less operative time, results in fewer complications, and offers an improved cosmetic result and greater patient satisfaction. Additional advantages of MIP are earlier hospital discharge and decreased overall associated costs. This article aims to address the considerations for accomplishing MIP, including the role of preoperative imaging studies, intraoperative adjuncts, and surgical techniques. PMID:26425454

  3. Immunochemical Localization of Parathyroid Hormone in Cancer Tissue from Patients with Ectopic Hyperparathyroidism

    PubMed Central

    Palmieri, Genaro M. A.; Nordquist, Robert E.; Omenn, Gilbert S.

    1974-01-01

    Immunoreactive parathyroid hormone (PTH) in nonparathyroid malignant tumors associated with hypercalcemia and hypophosphatemia in the absence of demonstrable bone metastases was determined by radioimmunoassay and immunofluorescent techniques. Six of seven tumors contained material with immunological cross-reactivity to bovine PTH by radioimmunoassay and immunofluorescence. The intensity of the immunofluorescent stain varied considerably in the different tumors. From 15 to 90% of neoplastic cells were stained specifically with fluorescein-labeled anti-PTH. In contrast, normal parathyroid glands and parathyroid adenomas showed uniform distribution of immunofluorescence in all parenchymal cells. In one malignant tumor, PTH was localized also by immunoautoradiography. In every case PTH was detected only in the cytoplasm of parenchymal cells. One patient lacked detectable PTH in his tumor, yet showed regression of the hypercalcemia to normal values after removal of large masses of neoplastic tissue and recurrence of hypercalcemia when new growth occurred. Dilutional radioimmunoassay curves of nonparathyroid malignant tumors were in most cases different from those obtained with extracts of normal parathyroid glands and parathyroid adenomas. Although both nonparathyroid neoplasmas and parathyroid extracts demonstrated immunoheterogeneity by gel filtration, greater heterogeneity was found in nonparathyroid malignant tumors. In those tumors in which immunological cross-reactivity to PTH was detected, the capability of secreting PTH may be restricted to derepressed cell clones amidst other neoplastic cells, whereas the greater heterogeneity of ectopic PTH may reflect hormone cleavage by proteolytic enzymes in the tumor that is less specific than the Pro-PTH cleaving enzyme in the parathyroids. Images PMID:4364410

  4. Parathyroid Carcinoma

    PubMed Central

    Givi, B.; Shah, J.P.

    2013-01-01

    Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. The cause is unknown, but clinical correlations with different genetic syndromes exist. Mutations in the HPRT2 gene seem to play a significant role in the pathogenesis of this disease. Men and women are equally affected, usually in the fourth or fifth decade of life. Most patients will present with signs and symptoms of hypercalcaemia. Cases of non-functioning carcinoma are exceedingly rare. Surgical resection is the most effective method of treatment and palliation. A significant proportion of patients will experience recurrence, and will need further surgical and, eventually, medical management of hypercalcaemia. The disease is progressive but slow growing. Most patients will require multiple operations to resect recurrent disease. The main cause of morbidity and mortality is the sequela of uncontrolled chronic hypercalcaemia rather than tumour burden. The current paper will review the epidemiology, pathogenesis, clinical presentation and diagnostic work-up of this disease. Surgical management in different scenarios is reviewed in detail, followed by other types of treatment and management of incurable disease. PMID:20510594

  5. Parathyroid biopsy (image)

    MedlinePlus

    ... be removed because of conditions such as a tumor or increased blood calcium levels. The parathyroid glands are located near the thyroid gland. They secrete parathyroid hormone (PTH), which functions ...

  6. Remedial Parathyroid Surgery

    PubMed Central

    Udelsman, Robert; Donovan, Patricia Irvin

    2006-01-01

    Objective: To review the outcomes in 130 consecutive remedial explorations for primary hyperparathyroidism. Summary Background Data: Remedial surgery for primary hyperparathyroidism is challenging and requires meticulous preoperative evaluation and imaging to expedite a focused surgical exploration that has traditionally been performed under general anesthesia. This prospective series of 130 consecutive remedial operations for primary hyperparathyroidism selectively used minimally invasive techniques and tested the hypothesis that these techniques could improve outcomes. Methods: Between 1990 and 2005, 1090 patients were evaluated and explored for primary hyperparathyroidism. Of these, 130 remedial explorations were performed in 128 patients who underwent either conventional exploration under general anesthesia (n = 107) or minimally invasive parathyroidectomy (n = 23) employing cervical block anesthesia, directed exploration, and curative confirmation with the rapid intraoperative parathyroid hormone assay. Results: The sensitivity of preoperative imaging were: Sestamibi (79%), ultrasound (74%), MRI (47%), CT (50%), venous localization (93%), and ultrasound guided parathyroid fine needle aspiration (78%). The cure rate in the conventional remedial group (n = 107) was 94% and was associated with a mean length of stay of 1.6 ± 0.2 days. Remedial exploration employing minimally invasive techniques (n = 23) resulted in a cure rate of 96% and a mean length of stay of 0.4 ± 0.1 days. Complications were rare in both remedial groups. These results were almost identical to those achieved in 960 unexplored patients. Conclusions: Remedial parathyroid surgery can be accomplished with acceptable cure and complication rates. Minimally invasive techniques can achieve outcomes that are similar to those obtained in unexplored patients. PMID:16926573

  7. Nonfunctional parathyroid carcinoma.

    PubMed Central

    Giessler, G. A.; Beech, D. J.

    2001-01-01

    Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with elevated serum levels of parathormone and calcium. These tumors may also be nonfunctional. Clinical detection of nonfunctioning parathyroid malignancies preoperatively is primarily based on symptoms of an expanding neck mass. This ominous complaint is typically accompanied with an advanced stage of the disease at initial diagnosis. Because there is a paucity of data in the literature regarding nonfunctioning parathyroid carcinoma, prognosis can not be readily assessed. In both functional and nonfunctional parathyroid carcinoma, early surgery has proven to be the only curative treatment approach whereas both chemotherapy and radiation therapy fail to produce systemic or regional benefit when used alone. Hence, parathyroid cancer should be considered in every patient evaluated for a neck mass regardless of the blood calcium and blood parathormone level. PMID:11491274

  8. Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients.

    PubMed Central

    Fukuda, N; Tanaka, H; Tominaga, Y; Fukagawa, M; Kurokawa, K; Seino, Y

    1993-01-01

    The resistance of parathyroid cells to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in uremic hyperparathyroidism is thought to be caused, in part, by a 1,25(OH)2D3 receptor (VDR) deficiency in the parathyroids. However, results of biochemical studies addressing VDR numbers in the parathyroids are controversial. Several studies have found VDR content to be decreased in the parathyroids of uremic patients and animals, while others have found no such decrease in the parathyroids of uremic animals. To clarify the role of VDR, we investigated VDR distribution in surgically-excised parathyroids obtained from chronic dialysis patients by immunohistochemistry. We classified the parathyroids as exhibiting nodular or diffuse hyperplasia. Our studies demonstrated a lower density of VDR in the parathyroids showing nodular hyperplasia than in those showing diffuse hyperplasia. Even in the parathyroids showing diffuse hyperplasia, nodule-forming areas were present; these areas were virtually negative for VDR staining. A significant negative correlation was found between VDR density and the weight of the parathyroids. These findings indicate that the conflicting results of biochemical studies may be caused by the heterogeneous distribution of VDR; the decreased VDR density in parathyroids may contribute to the progression of secondary hyperparathyroidism and to the proliferation of parathyroid cells that is seen in uremia. Images PMID:8397225

  9. Parathyroid diseases and animal models.

    PubMed

    Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

    2012-01-01

    CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies. PMID:22754549

  10. Intrapericardial parathyroid adenoma†

    PubMed Central

    Long, Kristin L.; Lee, Cortney Y.; Ramaiah, Chand; Sloan, David A.

    2013-01-01

    Primary hyperparathyroidism from a parathyroid adenoma is common. Ectopic parathyroid glands have been reported in numerous locations, including the chest. We present a single case report of an intrapericardial parathyroid gland found after failed bilateral neck exploration. The patient presented with severe, recurrent nephrolithiasis and acute renal failure prior to his surgical intervention. Repeat imaging identified a parathyroid adenoma in the mediastinum that was localized to the aortopulmonary window. After attempts at minimally invasive thoracotomy and posterolateral thoracotomy, a median sternotomy was ultimately required to identify the adenoma. PMID:24964470

  11. Parathyroid Hormone Levels and Cognition

    NASA Technical Reports Server (NTRS)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  12. Stages of Parathyroid Cancer

    MedlinePlus

    ... of the head and neck. SPECT scan (single photon emission computed tomography scan) : A procedure that uses ... a recurrence. The parathyroid cancer usually recurs between 2 and 5 years after the first surgery , but ...

  13. Parathyroid Cancer Treatment

    MedlinePlus

    ... of the head and neck. SPECT scan (single photon emission computed tomography scan) : A procedure that uses ... a recurrence. The parathyroid cancer usually recurs between 2 and 5 years after the first surgery , but ...

  14. Aluminum, parathyroid hormone, and osteomalacia

    SciTech Connect

    Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

    1983-01-01

    Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

  15. Parathyroid carcinoma: a silent presentation

    PubMed Central

    Lal, Karan; Chang, Robert; Mandava, Nageswara

    2014-01-01

    Primary hyperparathyroidism is most commonly diagnosed in the setting of benign parathyroid adenoma(s). However, it can also rarely be caused by parathyroid malignancy and when it is, the clinical manifestations far supercede the presentation of benign parathyroid adenoma. We report a case of suspected benign parathyroid adenoma induced primary hyperparathyroidism in which pathologic diagnosis of parathyroid carcinoma was made. Due to the lack of signs and symptoms, this indicates parathyroid malignancy can be masked clinically as benign adenomas, until a histologic diagnosis can be ascertained. PMID:25207215

  16. Coexisiting adenoma and granuloma involving the right inferior parathyroid gland with adjacent ectopic thymic tissue

    PubMed Central

    Gupta, Mayank; Kandasamy, Subramaniam

    2014-01-01

    Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. PMID:24957592

  17. Treatment Option Overview (Parathyroid Cancer)

    MedlinePlus

    ... not lung cancer. There is no standard staging process for parathyroid cancer. Parathyroid cancer is described as ... Clinical trials are part of the cancer research process. Clinical trials are done to find out if ...

  18. Nonfunctional parathyroid carcinoma.

    PubMed

    Nakamura, Yosuke; Kataoka, Hideyuki; Sakoda, Takema; Horie, Yasushi; Kitano, Hiroya

    2010-10-01

    A 65-year-old female patient was admitted to our hospital presenting with a superior mediastinal big mass that was elastic, hard, and painless. Laboratory data including serum calcium level and thyroid and parathyroid hormonal functions revealed no abnormalities. Further examination consisting of computed tomography, magnetic resonance imaging, and ultrasonography demonstrated that it was a solid tumor extending into the superior mediastinum. Technetium (Tc-99) sestamibi scan revealed a hypofunctioning focus in that area. The preoperative diagnosis was a thyroid tumor or a metastatic lymph node. Parathyroid carcinoma was suspected on intraoperative frozen pathological examination. The tumor was successfully removed with left thyroid lobectomy, and neck node dissection was performed. Macroscopically, it appeared as a dark reddish solid tumor, and the cut surface presented opalescence. Immunohistology confirmed that there was proliferation of tumor cells with positive chromogranin A staining. Thus, the tumor was diagnosed as parathyroid carcinoma histopathologically despite a lack of clinical evidence for hyperparathyroidism. This patient has been followed with no evidence of recurrence, a normal serum calcium 4 years after surgery, and postoperative radiotherapy. This report describes a case of nonfunctional parathyroid carcinoma with a massive mass that technetium (Tc-99) sestamibi scan failed to detect, and we showed negative immunostaining for parathyroid hormone (PTH) (N). PMID:20224881

  19. Associations of Sun Exposure with 25-Hydroxyvitamin D and Parathyroid Hormone Levels in a Cohort of Hypertensive Patients: The Graz Endocrine Causes of Hypertension (GECOH) Study

    PubMed Central

    Pilz, Stefan; Kienreich, Katharina; Stückler, Daniel; Meinitzer, Andreas; Tomaschitz, Andreas

    2012-01-01

    Sunlight-induced vitamin D, synthesis in the skin is the major source of vitamin D, but data on the relationship of sun-related behaviour with vitamin D and parathyroid hormone (PTH) levels are relatively sparse. We evaluated whether habitual sun exposure is associated with 25-hydroxyvitamin D (25[OH]D) and PTH levels and whether there exist seasonal variations. We examined 111 hypertensive patients in Austria (latitude 47° N). Frequent sunbathing at home and outdoor sports were associated with higher 25(OH)D levels (P < 0.05 for both). Red or blond scalp hair as a child, memory of sunburns, preferring sunbathing, frequent stays on the beach or in open-air pools, and solarium use were associated with lower PTH levels (P < 0.05 for all). Multiple linear regression analyses including age, sex, and body mass index showed that sun exposure score was significantly associated with 25(OH)D (beta coefficient = 0.27; P = 0.004) and by trend with PTH (beta coefficient = −0.16; P = 0.09). These associations were more prominent in summer in which 25(OH)D levels were significantly higher compared to winter. Translation of these findings into recommendations for the prevention and treatment of vitamin D deficiency remains a challenge for the future. PMID:22518130

  20. Thyroid and parathyroid imaging

    SciTech Connect

    Sandler, M.P.; Patton, J.A.; Partain, C.L.

    1986-01-01

    This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies. X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.

  1. Undescended parathyroid adenoma.

    PubMed

    Kanack, Melissa D; Maawy, Ali A; Oh, Deborah K; Bouvet, Michael

    2015-01-01

    Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222

  2. Polyclonality of Parathyroid Tumors in Neonatal Severe Hyperparathyroidism.

    PubMed

    Corrado, Kristin R; Andrade, Simone Caixeta; Bellizzi, Justin; D'Souza-Li, Lilia; Arnold, Andrew

    2015-10-01

    Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder characterized by major hypercalcemia, elevated parathyroid hormone levels, and marked enlargement of multiple parathyroid glands, usually associated with germline mutations in the calcium receptor gene CASR. However, little is known about the outgrowth of parathyroid tumors in NSHPT, including whether they represent monoclonal or polyclonal expansions. We sought to examine the clonality of parathyroid tissues resected from a patient with NSHPT and biallelic CASR mutations. DNA from two distinct parathyroid tumors resected from a girl with NSHPT, plus polyclonal/monoclonal control samples, were subjected to analyses of clonality by two independent methods, X-chromosome inactivation analysis at the androgen receptor locus (HUMARA) and BAC array comparative genomic hybridization (CGH). Both parathyroid tumor samples revealed polyclonal patterns by X-inactivation analysis, with polyclonal and monoclonal controls yielding the expected patterns. Similarly, by BAC array CGH, neither parathyroid sample contained monoclonal copy number changes and both appeared identical to the patient-matched polyclonal controls. Our observations provide direct experimental evidence that the markedly enlarged parathyroid tumors in the setting of NSHPT constitute polyclonal, generalized hyperplastic growths rather than monoclonal neoplasms. PMID:25828954

  3. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

    PubMed Central

    Miller, Gerald; Davis, James; Shatzen, Edward; Colloton, Matthew; Martin, David

    2012-01-01

    Background. Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. Methods. We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. Results. Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. Conclusions. The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH. PMID:22036941

  4. Normal parathyroid function with decreased bone mineral density in treated celiac disease.

    PubMed

    Lemieux, B; Boivin, M; Brossard, J H; Lepage, R; Picard, D; Rousseau, L; D'Amour, P

    2001-05-01

    Decreased bone mineral density (BMD) has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH) remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7+/-3.7 years (range 1.1 to 15.9). In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH) (3.77+/-0.88 pmol/L versus 2.28+/-0.63 pmol/L, P<0.001), which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score), patients had significantly lower BMDs of the hip (-0.60+/-0.96 SDs, P<0.05) and lumbar spine (-0.76+/-1.15 SDs, P<0.05). T scores were also decreased for the hip (-1.3+/-0.9 SDs, P<0.0001) and lumbar spine (-1.4+/-1.35 SDs, P<0.0001), with two to three patients being osteoporotic (T score less than -2.5 SDs) and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs) in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not

  5. Genetic characterization of large parathyroid adenomas

    PubMed Central

    Sulaiman, Luqman; Nilsson, Inga-Lena; Juhlin, C Christofer; Haglund, Felix; Höög, Anders; Larsson, Catharina; Hashemi, Jamileh

    2012-01-01

    In this study, we genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated in our institution during 2005–2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (P<0.001). Further analysis of 21 LPTAs revealed low MIB1 proliferation index (0.1–1.5%), MEN1 mutations in five cases, and one HRPT2 (CDC73) mutation. Total or partial loss of parafibromin expression was observed in ten tumors, two of which also showed loss of APC expression. Using array CGH, we demonstrated recurrent copy number alterations most frequently involving loss in 1p (29%), gain in 5 (38%), and loss in 11q (33%). Totally, 21 minimal overlapping regions were defined for losses in 1p, 7q, 9p, 11, and 15q and gains in 3q, 5, 7p, 8p, 16q, 17p, and 19q. In addition, 12 tumors showed gross alterations of entire or almost entire chromosomes most frequently gain of 5 and loss of chromosome 11. While gain of 5 was the most frequent alteration observed in LPTAs, it was only detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A significant positive correlation was observed between parathyroid hormone level and total copy number gain (r=0.48, P=0.031). These results support that LPTAs represent a group of patients with pronounced parathyroid hyperfunction and associated with specific genomic features. PMID:22454399

  6. Prospective associations of vitamin D status with β-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status.

    PubMed

    Kramer, Caroline K; Swaminathan, Balakumar; Hanley, Anthony J; Connelly, Philip W; Sermer, Mathew; Zinman, Bernard; Retnakaran, Ravi

    2014-11-01

    Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer β-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of β-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis. PMID:24875346

  7. The history of parathyroid endocrinology

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Sahay, Rakesh; Sawhney, Kanishka

    2013-01-01

    The parathyroid glands are now recognized as being essential for life. Their structure and function is well delineated, and their disease and dysfunction, well characterized. Diagnosis and management of parathyroid disease has improved in the past few decades. The path of parathyroid science, however, has been far from smooth. This paper describes the early history of parathyroid endocrinology. In doing so, it focuses on major events and discoveries, which improved the understanding and practice of our specialty. Contribution in anatomy, physiology, pathology, medicine, surgery and biochemistry are reviewed. PMID:23776911

  8. The history of parathyroid endocrinology.

    PubMed

    Kalra, Sanjay; Baruah, Manash P; Sahay, Rakesh; Sawhney, Kanishka

    2013-03-01

    The parathyroid glands are now recognized as being essential for life. Their structure and function is well delineated, and their disease and dysfunction, well characterized. Diagnosis and management of parathyroid disease has improved in the past few decades. The path of parathyroid science, however, has been far from smooth. This paper describes the early history of parathyroid endocrinology. In doing so, it focuses on major events and discoveries, which improved the understanding and practice of our specialty. Contribution in anatomy, physiology, pathology, medicine, surgery and biochemistry are reviewed. PMID:23776911

  9. Spontaneous cervical haemorrhage of a parathyroid adenoma

    PubMed Central

    Knee, Graham; Todd, Colin

    2015-01-01

    Summary Haemorrhage of a parathyroid adenoma is a rare clinical presentation. This report describes a previously fit and well 54-year-old woman who presented with acute neck swelling and pain with an overlying ecchymosis. Admission laboratory tests revealed a raised parathyroid hormone and hypercalcaemia. A computed tomography (CT) scan showed widespread anterior cervical haemorrhage and a lesion at the inferior pole of the left thyroid gland. A working diagnosis of spontaneous haemorrhage from a parathyroid adenoma was made. As she was haemodynamically stable, she was treated conservatively with a period of observation in hospital to monitor for signs of neck organ compression. Follow-up imaging with CT, ultrasound and sestamibi confirmed the likely source of haemorrhage as a parathyroid nodule with significant vascularity. The diagnosis was confirmed on histopathological analysis after elective surgical exploration of the neck 6 months after her presentation. This revealed a benign parathyroid adenoma with evidence of acute and chronic bleeding. The patient made a full recovery with immediate normalisation of her biochemistry post-operatively. Despite developing a hoarse voice in the immediate post-operative period, this resolved completely within 1 month. This case report provides further evidence to support a minimal delay for elective surgery after conservative management to reduce the risks associated with recurrent bleeding. Learning points Haemorrhage of a parathyroid adenoma should be a differential for all cases of acute cervical swelling or ecchymosis with no precipitating factor.The clerking should identify any risk factors for endocrine disease.Blood tests to screen for abnormal parathyroid biochemistry should be performed on admission.Detailed imaging of the neck is essential to identify the source of haemorrhage and risk of compression to vital neck organs.Conservative management is a suitable option for patients who remain haemodynamically stable

  10. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status [25(OH)D], parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose...

  11. Improvement of calcium balance by Fructus Ligustri Lucidi extract in mature female rats was associated with the induction of serum parathyroid hormone levels.

    PubMed

    Dong, Xiao-Li; Zhao, Ming; Wong, Kwun-Kit; Che, Chun-Tao; Wong, Man-Sau

    2012-07-14

    Fructus Ligustri Lucidi (FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague-Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague-Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats. PMID:22018100

  12. Association between vitamin D status and serum parathyroid hormone concentration and calcaneal stiffness in Japanese adolescents: sex differences in susceptibility to vitamin D deficiency.

    PubMed

    Tsugawa, Naoko; Uenishi, Kazuhiro; Ishida, Hiromi; Ozaki, Reo; Takase, Tomoki; Minekami, Takuya; Uchino, Yuri; Kamao, Maya; Okano, Toshio

    2016-07-01

    There is currently insufficient information on serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and bone mineral status in healthy adolescents to allow reference values to be set. This study aimed to provide comparable data on vitamin D status in Japanese adolescents and to assess sex differences in susceptibility to vitamin D insufficiency. Serum 25OHD and PTH concentrations were measured in 1,380 healthy adolescents (aged 12-18 years). Subjects completed a questionnaire on exercise history, diet, and lifestyle factors. Calcaneal stiffness was evaluated by quantitative ultrasound. Serum 25OHD concentrations in boys and girls were 60.8 ± 18.3 and 52.8 ± 17.0 nmol/L, respectively. Approximately 30 % of boys and 47 % of girls had suboptimal 25OHD concentrations (<50 nmol/L). Serum PTH concentration was negatively correlated with serum 25OHD concentration in boys, but negatively correlated with calcium intake rather than serum 25OHD in girls. In contrast, the increment in calcaneal stiffness as a result of elevation of serum 25OHD was higher in girls than in boys. As vitamin D deficiency is common in Japanese adolescents, it was estimated that intakes of ≥12 and ≥14 μg/day vitamin D would be required to reach 25OHD concentrations of 50 nmol/L in boys and girls, respectively. Moreover, the results of the present study indicate that vitamin D deficiency has a greater association with calcaneal stiffness in girls than in boys. PMID:26260151

  13. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China.

    PubMed

    Zhang, Qiao; Shi, Lixin; Peng, Nianchun; Xu, Shujing; Zhang, Miao; Zhang, Song; Li, Hong; Zhuang, Huijun; Gong, Mingxian; Wu, Danrong; Wang, Rui

    2016-03-28

    Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57°), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12·6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0·207, P=0·003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0·004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l. PMID:26843386

  14. Thyroid and parathyroid imaging.

    PubMed

    Freitas, J E; Freitas, A E

    1994-07-01

    With the advent of better thyroid function tests, a tumor marker, and fine-needle aspiration, the role of thyroid imaging studies in the evaluation of the patients with thyroid disease has diminished. Although multimodality thyroid imaging had improved our understanding of thyroid disease, current indications for thyroid imaging are the solitary or dominant thyroid nodule, an upper mediastinal mass, differentiation of hyperthyroidism, detection and staging of postoperative thyroid cancer, neonatal hypothyroidism, thyroid developmental anomalies, and the thyroid mass post-thyroidectomy for benign disease. To provide optimal, cost-effective, care for the thyroid patient, the physician must understand the advantages and disadvantages of each imaging modality--scintigraphy, real-time sonography (RTS), computed tomography, and magnetic resonance--in specific clinical settings. Similarly, preoperative noninvasive localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism undergoing their initial neck exploration usually is not warranted. In this situation, the best localization procedure is to enlist the services of an experienced parathyroid surgeon. However, if this is not feasible because of local constraints, both sestamibi methoxy isobutyl isonitrile (MIBI) scintigraphy and magnetic resonance imaging (MRI) provide excellent localization (< 90%) of juxta-thyroidal and ectopic parathyroid adenomas. Hyperplastic glands are more difficult to detect because of their smaller size, and tandem studies (MIBI and MRI) should provide higher sensitivity before initial exploration, especially in patients with ectopic glands. In patients with persistent or recurrent disease, multimodality imaging with MIBI, MR, computed tomography and RTS in a sequential fashion is warranted to optimize two-test, site-specific localization. PMID:7973759

  15. Concurrent papillary thyroid cancer and parathyroid adenoma as a rare condition: a case report.

    PubMed

    Javadi, Hamid; Jallalat, Sara; Farrokhi, Shokrollah; Semnani, Shahriar; Mogharrabi, Mehdi; Riazi, Ahmad; Nabipour, Iraj; Moshtaghi, Darab; Assadi, Majid

    2012-01-01

    Although the pathological relationship between parathyroid and thyroid diseases is common, an association between parathyroid adenoma and thyroid cancer is rare. Concomitant thyroid cancer in patients with primary hyperparathyroidism (pHPT) has been reported at varying frequencies. WE present here a 23-year-old man who had papillary thyroid carcinoma in the right thyroid lobe and a parathyroid adenoma in the left thyroid lobe, which were confirmed surgically. PMID:22936512

  16. Diagnostic value of GATA-3 in cytological identification of parathyroid tissues.

    PubMed

    Takada, Nami; Hirokawa, Mitsuyoshi; Suzuki, Ayana; Higuchi, Miyoko; Kuma, Seiji; Miyauchi, Akira

    2016-07-30

    Parathyroid and thyroid lesions appear morphologically similar in cytological smears, and their differentiation can be difficult. The purpose of this study was to determine the diagnostic value of T-cell-specific transcription factor GATA-3 as a marker of parathyroid differentiation in cytology specimens, and to examine the utility of liquid-based cytology (LBC). Cytology smears obtained from surgically removed parathyroid and thyroid specimens, including 15 normal parathyroid glands, 12 cases of parathyroid hyperplasia, 55 parathyroid adenomas, 2 follicular thyroid adenomas, and 3 papillary thyroid carcinomas, were examined by immunocytochemistry using antibodies against GATA-3, parathyroid hormone (PTH), chromogranin A, and thyroid transcription factor 1 (TTF-1). All normal and hyperplastic parathyroids and 98.2% of parathyroid adenomas were positive for GATA-3, while 33.3%, 66.7%, and 60.0% of them, respectively, were positive for PTH. The positive rates for chromogranin A among normal parathyroids (80.0%) and parathyroid adenomas (87.3%) were lower than those for GATA-3. At the same time, all thyroid-derived tumours were positive for TTF-1 and negative for GATA-3, PTH, and chromogranin A. LBC smears of 35 parathyroid lesions indicated that the positive rates for GATA-3, PTH, and chromogranin A were 97.1 %, 97.1%, and 100%, respectively, while in conventional smears, those for PTH (25.5%) and chromogranin A (78.7%) were significantly lower (p < 0.01). Our results suggest that GATA-3 is a more reliable biomarker than PTH or chromogranin A in differentiating parathyroid from thyroid lesions in cytology smears and that LBC is useful in detecting cytoplasmic antigens such as PTH and chromogranin A. PMID:27097544

  17. Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

    PubMed

    Wong, Yin Ping; Sharifah, Noor Akmal; Tan, Geok Chin; Gill, Anthony James; Ali, Syed Z

    2016-08-01

    Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016;44:688-692. © 2016 Wiley Periodicals, Inc. PMID:27229757

  18. A middle aged lady with recurrent low trauma fracture due to parathyroid adenoma.

    PubMed

    Saifuddin, M; Selim, S; Haq, T; Shefin, S M; Latif, Z A

    2015-01-01

    A 48 year old lady was referred to BIRDEM Hospital, Dhaka, Bangladesh by her local physician for evaluation of hypercalcaemia and increased serum parathyroid hormone (PTH) in the background history of low trauma fracture. Ultrasound of neck and parathyroid scintigraphy with 99mTc-MIBI revealed a parathyroid adenoma. Parathyroidectomy was done. Histopathology report showed features consistent with parathyroid adenoma. Primary hyperparathyroidism should be kept in mind in all patients presenting with history of bone problems ranging from simple bone pain to spontaneous or low trauma fracture associated with hypercalcemia. By the help of appropriate localization technique it can be localized and cured by parathyriodectomy. PMID:25725690

  19. Phantom experiments to improve parathyroid lesion detection

    SciTech Connect

    Nichols, Kenneth J.; Tronco, Gene G.; Tomas, Maria B.; Kunjummen, Biju D.; Siripun, Lisa; Rini, Josephine N.; Palestro, Christopher J.

    2007-12-15

    This investigation tested the hypothesis that visual analysis of iteratively reconstructed tomograms by ordered subset expectation maximization (OSEM) provides the highest accuracy for localizing parathyroid lesions using {sup 99m}Tc-sestamibi SPECT data. From an Institutional Review Board approved retrospective review of 531 patients evaluated for parathyroid localization, image characteristics were determined for 85 {sup 99m}Tc-sestamibi SPECT studies originally read as equivocal (EQ). Seventy-two plexiglas phantoms using cylindrical simulated lesions were acquired for a clinically realistic range of counts (mean simulated lesion counts of 75{+-}50 counts/pixel) and target-to-background (T:B) ratios (range=2.0 to 8.0) to determine an optimal filter for OSEM. Two experienced nuclear physicians graded simulated lesions, blinded to whether chambers contained radioactivity or plain water, and two observers used the same scale to read all phantom and clinical SPECT studies, blinded to pathology findings and clinical information. For phantom data and all clinical data, T:B analyses were not statistically different for OSEM versus FB, but visual readings were significantly more accurate than T:B (88{+-}6% versus 68{+-}6%, p=0.001) for OSEM processing, and OSEM was significantly more accurate than FB for visual readings (88{+-}6% versus 58{+-}6%, p<0.0001). These data suggest that visual analysis of iteratively reconstructed MIBI tomograms should be incorporated into imaging protocols performed to localize parathyroid lesions.

  20. Considerations in parathyroid hormone testing.

    PubMed

    Cavalier, Etienne; Plebani, Mario; Delanaye, Pierre; Souberbielle, Jean-Claude

    2015-11-01

    Parathyroid hormone (PTH) is a major player in phosphocalcic metabolism and its measurement is very important for the correct diagnosis and treatment of several diseases. PTH determination represents the paradigm of quality in laboratory medicine as many variables in the pre-, intra-, and post-analytical phases strongly affect the value of the clinical information. Analytical determination of PTH has been rendered difficult by the presence, in the circulation, of truncated fragments that can cross-react with the antibodies used for its determination. In addition, pre-analytical phase is complicated by the lack of stability of the peptide and the best sample to use for its determination remains controversial, as well as sample handling and storage. PTH secretion is also affected by circadian and seasonal rhythms and by physical exercise. Finally, from the post-analytical perspective, establishment of reliable reference ranges requires further efforts as the selection criteria for reference subjects should take into consideration new variables such as gender, race and vitamin D levels. Finally, clinical guidelines have recently revised and improved the criteria for a correct interpretation of PTH values. PMID:26035114

  1. Parathyroid hormone (PTH) blood test

    MedlinePlus

    ... in the blood Radiation to the parathyroid glands Sarcoidosis Excess vitamin D intake Other conditions for which ... I Multiple endocrine neoplasia (MEN) II Osteomalacia Rickets Sarcoidosis Update Date 10/28/2015 Updated by: Brent ...

  2. Medical management after parathyroid intervention

    PubMed Central

    Tanaka, Motoko; Fukagawa, Masafumi

    2008-01-01

    Vitamin D or vitamin D analogues pulse therapy is seldom effective in patients with at least one parathyroid gland with nodular hyperplasia, and surgical parathyroidectomy or parathyroid intervention is indicated. In parathyroid interventions, especially in selective percutaneous ethanol injection therapy (PEIT), the enlarged parathyroid gland(s) with nodular hyperplasia is selectively destroyed by ethanol injection, while other glands with diffuse hyperplasia are managed by medical therapy. Thus, medical management, e.g., use of appropriate dose of vitamin D or vitamin D analogues after the PEIT procedure, is as important as the destruction of the hyperplastic tissue itself. Recent studies showed that the combination of PEIT and intravenous vitamin D pulse therapy lead to reduce serum PTH level and calcium-phosphorus products in haemodialysis patients. In this article, we focus on the importance of medical therapy after PEIT, and review the efficacy of the combination of PEIT and intravenous vitamin D pulse therapy for haemodialysis patients with secondary hyperparathyroidism. PMID:25983966

  3. General Information about Parathyroid Cancer

    MedlinePlus

    ... of the head and neck. SPECT scan (single photon emission computed tomography scan) : A procedure that uses ... a recurrence. The parathyroid cancer usually recurs between 2 and 5 years after the first surgery , but ...

  4. Parathyroid hormone-related protein blood test

    MedlinePlus

    ... gov/ency/article/003691.htm Parathyroid hormone-related protein blood test To use the sharing features on ... page, please enable JavaScript. The parathyroid hormone-related protein (PTH-RP) test measures the level of a ...

  5. Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome.

    PubMed

    Posada-González, María; Gómez-Ramírez, Joaquín; Luque-Ramírez, Manuel; Guijarro, Mercedes; Martín-Pérez, Elena; Rodríguez-Sánchez, Ana; García-Sanz, Iñigo; Larrañaga, Eduardo

    2014-01-01

    Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1) and 2A (MEN-2A) syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome. PMID:25374962

  6. Evaluation of parathyroid autograft growth and function in hemodialysis patients

    SciTech Connect

    Karsenty, G.; Petraglia, A.; Bourdeau, A.; Gambini, D.J.; Moreau, J.F.; Lecharpentier, Y.; Zingraff, J.; Bournerias, F.; Buisson, C.; Dubost, C.

    1986-07-01

    The aim of our study was to evaluate the function and growth of parathyroid tissue autografted into the forearm of hemodialysis patients using several presently available methods. In a dynamic study, the secretory function of autografted tissue was evaluated in seven patients using either zero calcium dialysate or calcium infusion. In an additional prospective study, seven patients had repeated determinations of plasma immunoreactive parathyroid hormone (iPTH) concentration on samples from both forearms, a radionuclide evaluation of autograft function using thallium-201 chloride, and real time ultrasonography. Light microscopy analysis was performed in two patients. The dynamic study demonstrated that induction of hypocalcemia was followed by an increase, and induction of hypercalcemia by a decrease in circulating iPTH in both forearms using three different radioimmunoassays similar to what has been reported for normal parathyroid tissue. A significant gradient (ie, greater than 2.0) of plasma iPTH concentration in samples from both forearms was observed in only three out of the seven patients of the prospective study. Two of these patients disclosed an increased uptake of /sup 201/TI chloride at the site of autografted tissue and had an echographically detectable mass. In both, hyperplastic parathyroid tissue was removed. At present, the remaining third patient does not have other features of recurrent hyperparathyroidism. In conclusion, autotransplanted parathyroid tissue of hemodialysis patients shows an adequate response to physiologic stimuli such as hypo- and hypercalcemia. Dynamic tests, therefore, appear to be a useful tool in the assessment of its function. In addition, radionuclide and echographic studies may be reliable adjuncts in the detection of marked parathyroid autograft hyperplasia.

  7. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight

    PubMed Central

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-01-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. PMID:25648860

  8. Intrathyroidal parathyroid carcinoma mimicking a thyroid nodule in a MEN type 1 patient.

    PubMed

    Lee, Kyung Mi; Kim, Eui Jong; Choi, Woo Suk; Park, Won Seo; Kim, Sung Won

    2014-05-01

    A 59-year-old woman with classic manifestations of hyperparathyroidism associated with multiple endocrine neoplasia type 1 presented with a right adrenal mass and two pituitary microadenomas on imaging studies. For evaluation of hypercalcemia, (99m) Tc-MIBI scintigraphy was done and showed focal uptake at the thyroid level of the right anterior neck. Subsequent neck sonography showed several thyroid nodules, but there was no parathyroid tumor. Percutaneous fine-needle aspiration of the dominant thyroid nodule indicated a follicular nodule. After surgery, final histopathology revealed intrathyroidal parathyroid carcinoma. This case illustrates the difficulty in diagnosing parathyroid carcinoma via fine-needle aspiration. PMID:24037737

  9. Hyperparathyroidism with a functioning parathyroid cyst.

    PubMed

    Ak, Ilknur; Acikalin, Mustafa Fuat

    2007-09-01

    A rare case of primary hyperparathyroidism with a functioning parathyroid cyst in whom Tc-99m MIBI scintigraphy failed to detect a parathyroid tumor is presented. A 62-year-old woman with primary hyperparathyroidism was referred for Tc-99m MIBI imaging to investigate a parathyroid adenoma. Plasma levels of intact parathyroid hormone were elevated to 2250 pg/mL. Neck ultrasonography revealed a cystic lesion measured 30 x 42 x 35 mm on the right inferior side of the thyroid gland. The cystic lesion was successfully removed at surgery. Pathologic diagnosis revealed a benign parathyroid cyst. The cyst contained clear fluid, and was lined by 1 layer of cuboidal epithelial cells. Her postoperative course was uneventful and plasma levels of intact parathyroid hormone normalized after operation. PMID:17710026

  10. Parathyroid adenoma in patients with Graves' disease: a report of 21 cases.

    PubMed

    Wei, Shuanzeng; Baloch, Zubair W; LiVolsi, Virginia A

    2015-03-01

    Graves' disease (GD) is frequently associated with mild hypercalcemia. The hypercalcemia may be due to the activation of osteoclastic bone resorption caused by the excess thyroid hormone. In some cases of GD, the hypercalcemia can be attributable to concomitant parathyroid diseases. In this study, 21 patients with a history of GD developed parathyroid adenoma based on histology, intraoperative parathyroid hormone (IOPTH) monitoring, and other clinical features. There were 11 patients with a history of radioactive iodine therapy (RAI) for GD. The latency time of RAI was from 12 to 41 years. The case cohort was divided into two groups: patients with (group GR: 11 patients) and patients without a history of RAI (group G: 10 patients). Mean age of patients in group GR was 54.8 years compared to 62.2 years of group G (P = 0.08). There were no statistically significant differences regarding the parathyroid weight, serum calcium, and pre- and post-parathyroidectomy PTH levels. There was no histopathologic difference between the two groups. In conclusion, we report 21 cases of parathyroid adenoma in patients with Graves' disease. There may be a possible link between GD patients with a RAI history and an increased risk of parathyroid adenoma. The parathyroid adenomas showed no clinicopathological differences between GD patient with and without a history of RAI. PMID:25501495

  11. Effect of phorbol myristate acetate on secretion of parathyroid hormone

    SciTech Connect

    Morrissey, J.J. )

    1988-01-01

    The influence of phorbol myristate acetate (PMA), an activator of protein kinase c, on the secretion of parathyroid hormone from collagenase-dispersed bovine parathyroid cells was tested. The cells were incubated at low or high concentrations of calcium in the medium, and the hormone secreted into the medium was measured by a radioimmunoassay that recognizes both intact and C-terminal fragments of hormone. A stimulatory effect of PMA at high calcium, seen at PMA concentrations as low as 1.6 nM, did not occur with a biologically inactive 4{alpha}-isomer of phorbol ester, and was independent of changes in cellular adenosine 3{prime},5{prime}-cyclic monophosphate levels. Examination of {sup 32}P-labeled phosphoproteins by two-dimensional gel electrophoresis revealed acidic proteins of {approximately}20,000 and 100,000 Da that were phosphorylated at low and high calcium + 1.6 {mu}M PMA but not at high calcium alone. The protein kinase c activity associated with the membrane fraction of parathyroid cells significantly decreased 40% when the cells were incubated at high vs. low calcium. The data suggest that calcium may regulate parathyroid hormone secretion through changes in protein kinase c activity of the membrane fraction of the cell and protein phosphorylation.

  12. Parathyroid cysts: a clinical and radiological challenge.

    PubMed

    Witherspoon, Jolene; Lewis, Michael

    2012-02-01

    Parathyroid cysts are rare causes of neck swelling accounting for 0.6% of thyroid and parathyroid lesions. They may be functional, resulting in the release of parathyroid hormone, or non-functional. Non-functional cysts may be cosmetically unacceptable or cause dysphagia, dyspnoea or recurrent laryngeal nerve palsy as a result of compression. This article presents a young woman who was diagnosed with a thyroid cyst both on examination and imaging. However, the final histology confirmed this to be parathyroid in origin and this should be considered in the differential of such neck swellings. PMID:22504755

  13. Amphibian parathyroids: morphological and functional aspects.

    PubMed

    Srivastav, A K; Das, V K; Das, S; Sasayama, Y; Suzuki, N

    1995-10-01

    Amphibians living partially or totally in a terrestrial environment are the first tetrapods to possess parathyroid glands. Purely aquatic amphibians and amphibian larvae lack these endocrine glands. The parathyroids develop at the time of metamorphosis. The parathyroid glands in caecilians consist of a single cell type, that of urodeles may be composed of basal (supporting) cells and suprabasal (chief) cells, and that of anurans of small and large chief cells. Parathyroid glands of caecilians and anurans lack connective tissue, blood vessels, and nerves. The parathyroid cells become activated in response to decreased blood calcium concentration and undergo changes indicating increased parathyroid hormone secretion. Increased blood calcium concentration suppresses secretory activity. Usually, parathyroidectomy elicits hypocalcemia in most amphibians. Such operations have no effect in lower urodeles. Parathyroid hormone administration provokes hypercalcemia in most amphibians. The parathyroids of caecilians have not been studied in detail. The urodeles and anurans exhibit seasonal changes in the parathyroid glands. These changes may be initiated by environmental stimuli such as light, temperature, or alterations in blood calcium levels caused by natural hibernation. PMID:8580512

  14. Optimal scan time for evaluation of parathyroid adenoma with [18F]-fluorocholine PET/CT

    PubMed Central

    Rep, Sebastijan; Lezaic, Luka; Kocjan, Tomaz; Pfeifer, Marija; Sever, Mojca Jensterle; Simoncic, Urban; Tomse, Petra; Hocevar, Marko

    2015-01-01

    Background Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [18F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism. Patients and methods. 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated. Results Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05). Conclusions According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH. PMID:26834518

  15. Current applications of the intraoperative parathyroid hormone assay in parathyroid surgery.

    PubMed

    Richards, Melanie L; Grant, Clive S

    2007-04-01

    Parathyroid hormone measurement using a two-site immunochemiluminometric assay has allowed for a rapid and accurate technique that has found its way into the operative armamentarium of some parathyroid surgeons. It can be used to assess the completeness of parathyroid gland resection and allow for a minimally invasive parathyroidectomy. This operative approach has become a popular marketing tool, providing patients with confidence in their surgical outcome. The purpose of this review is to provide the surgeon with the practical points and pitfalls of the use of intraoperative parathyroid hormone in the treatment of parathyroid disease. PMID:17439020

  16. Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis

    PubMed Central

    2013-01-01

    Background Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies. Methods We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels. Results A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89). Conclusions Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates. PMID:23594621

  17. Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions

    PubMed Central

    Dimashkieh, Haytham; Krishnamurthy, Savitri

    2006-01-01

    Background Parathyroid gland and their tumors comprise a small proportion of non-palpable neck masses that are investigated by ultrasound (US) guided fine needle aspiration biopsy. We reviewed our institution's cases of US guided FNAB of parathyroid gland and their lesions to determine the role of cytology for the preoperative diagnosis of parathyroid gland and their lesions. Method All cases of FNAB of parathyroid gland and lesions in the last 10 years were reviewed in detail with respect to clinical history and correlated with the histopathologic findings in available cases. The cytologic parameters that were evaluated included cellularity assessed semiquantitatively as scant, intermediate or abundant (<50, 51–500 or >500 cells), cellular distribution (loose clusters, single cells/naked nuclei, rounded clusters, two- and three-dimensional clusters, and presence of prominent vascular proliferation), cellular characteristics (cell size, nuclear shape, presence/absence of a nucleolus, degree of mitosis, amount of cytoplasm, and appearance of nuclear chromatin), and background (colloid-like material and macrophages). Immunostaining for parathyroid hormone (PTH) was performed on selected cases using either destained Pap smears or cell block sections. Results Twenty cases of US-guided FNAB of parathyroid glands and their lesions including 13 in the expected locations in the neck, 3 in intrathyroid region, 3 in thyroid bed, and 1 metastatic to liver were studied. Majority of the cases showed intermediate cellularity (51–500 cells) with round to oval cells that exhibited a stippled nuclear chromatin, without significant pleomorphism or mitotic activity. The cells were arranged in loose two dimensional groups with many single cells/naked nuclei around the groups. Occasionally macrophages and colloid like material was also encountered. There was no significant difference in the cytomorphologic features between normal gland, hyperplasia adenoma, or carcinoma

  18. Original technique for preoperative preparation of patients and intraoperative localization of parathyroid adenomas.

    PubMed

    Pasta, V; Monteleone, F; Del Vecchio, L; Iacobelli, S; Urciuoli, P; D'Orazi, V

    2015-01-01

    Surgical approach of single parathyroid adenoma treatment is turning to a less invasive surgery, allowing us to obtain better aesthetic results, reduction of duration of surgical operation, reduction of post-operative morbidity and hospital stay. Tc99m-sestaMIBI scintigraphy is mainly performed for preoperative localization of parathyroid adenomas. Our technique is instead based on the possibility to inhibit the interference of Tc99m-sestaMIBI uptake of the thyroid gland by means of the administration of Lugol's solution. Indeed, to confirm the identification and removal of the hyperfunctional parathyroid, it is accepted as adequate an ex vivo radioactivity count of the adenoma 20% or 40% greater than the value of the post-excisional background radioactivity, in association or not with intraoperative measurement of PTH. This method allows us to perform surgery with no timetable restriction, and to clearly distinguish the radioactivity of parathyroid adenoma from that of the surrounding tissues and thyroid gland. PMID:26188752

  19. [Lithium carbonate-induced hyperparathyroidism in a patient after removal of a parathyroid adenoma].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    Lithium compounds are widely used and effective drugs in the treatment of mood disorders. However, despite their efficacy, the use of lithium salts is limited by their narrow therapeutic window. Treatment with lithium salts may be associated with the risk of development of numerous adverse effects. Endocrine complications include: thyroid dysfunction, nephrogenic diabetes insipidus and hyperparathyroidism. Because symptoms of lithium-induced hyperparathyroidism may resemble those of the underlying disorder, hyperparathyroidism sometimes remains undetected. The pathogenic mechanism for parathyroid dysfunction in lithium-treated patients is still unclear. We report a patient who had undergone removal of a parathyroid adenoma and later developed lithium-induced hyperparathyroidism. Cessation of lithium treatment normalised parathyroid function. The described case suggests that patients with pre-existing parathyroid disorders may be particularly susceptible to the development of lithium-induced hyperparathyroidism. PMID:26094339

  20. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  1. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  2. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  3. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  4. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  5. Childhood parathyroid adenoma: a rare but important cause of nephrolithiasis.

    PubMed

    Menon, Prema; Dayal, Devi; Rao, Suhitha G; Bhattacharya, Anish; Narasimha Rao, Katragadda Lakshmi

    2016-07-01

    Primary hyperparathyroidism is very rare in children and adolescents. The management of a 12-year-old boy with renal calculi due to parathyroid adenoma is discussed. The single tumor after localization with sestamibi scintigraphy and SPECT-CT scan was excised with amelioration of symptoms. The case is reported due to the rarity of the disease and successful unilateral exploration. The association with hypopigmented areas of skin has also not been previously reported in literature. PMID:27054596

  6. Evidence-Based Workflows for Thyroid and Parathyroid Surgery

    PubMed Central

    Meltzer, Charles; Budayr, Amer; Chavez, Annette; Dlott, Richard; Greif, William; Gurushanthaiah, Deepak; Klonecke, Andrew; Lando, Matthew; Leary, Joyce; Nayak, Sundeep; Niederkohr, Ryan; Park, Judith; Savitz, Alison; Schwartz, Henry

    2016-01-01

    A need exists to reduce care variations by standardizing the practice of thyroid and parathyroid surgery. During the course of a year, a task force developed algorithms representing decision points and workflows based on American Thyroid Association guidelines and three internal studies of surgical practices in the Northern and Southern California Regions of Kaiser Permanente conducted in collaboration with Health Information Technology Transformation & Analytics (HITTA). PMID:27479948

  7. Evidence-Based Workflows for Thyroid and Parathyroid Surgery.

    PubMed

    Meltzer, Charles; Budayr, Amer; Chavez, Annette; Dlott, Richard; Greif, William; Gurushanthaiah, Deepak; Klonecke, Andrew; Lando, Matthew; Leary, Joyce; Nayak, Sundeep; Niederkohr, Ryan; Park, Judith; Savitz, Alison; Schwartz, Henry

    2016-01-01

    A need exists to reduce care variations by standardizing the practice of thyroid and parathyroid surgery. During the course of a year, a task force developed algorithms representing decision points and workflows based on American Thyroid Association guidelines and three internal studies of surgical practices in the Northern and Southern California Regions of Kaiser Permanente conducted in collaboration with Health Information Technology Transformation & Analytics (HITTA). PMID:27479948

  8. The reasons for failure in parathyroid operations.

    PubMed

    Levin, K E; Clark, O H

    1989-08-01

    Primary hyperparathyroidism occurs in about 1 in every 700 individuals. We analyzed our experience with 81 patients with persistent or recurrent hyperparathyroidism who were treated at the University of California, San Francisco, and the Veterans Administration Medical Center, San Francisco, from January 1979 through September 1988. In the 89 reoperations performed, the following six reasons or combination of reasons were responsible for the failed initial operation: (1) in 50 patients, there were multiple abnormal glands (30 hyperplastic and 20 second adenoma); (2) in 40 patients, the tumor was located in an ectopic position (22 mediastinal, 9 deep-seated cervical, 7 intrathyroidal, and 2 undescended); (3) in 17 patients, there were supernumerary parathyroid glands; (4) in 12 patients, the abnormal parathyroid glands were found in normal locations and the tumors were missed because of surgeon inexperience; (5) in 4 patients, failure was due to metastatic parathyroid cancer; and (6) in 4 patients, failure was due to errors on frozen section examinations. Preoperative localization studies usually identified the abnormal parathyroid tumor(s) prior to reoperations and were helpful in these patients. Knowledge of the reasons for failed parathyroid operations and the usual and unusual sites where parathyroid tumors are situated as well as a complete exploration should decrease the frequency of failed parathyroid operations. Localization studies are helpful for identifying these often elusive tumors. PMID:2757503

  9. Parathyroid autotransplantation in rats having hypoparathyroidism

    PubMed Central

    Erikoglu, Mehmet; Colak, Bayram; Toy, Hatice; Gurbilek, Mehmet

    2015-01-01

    Re-implantation techniques of extracted parathyroid tissue were developed in order to prevent temporary hypocalcemia. During thyroid surgery; inadvertently removed or devascularized parathyroid gland is usually implanted in the sternocleidomastoid muscle. In this experimental study using rats with hypoparathyroidism, our aim was to investigate whether the excised parathyroid tissue could be seeded in the liver and in the peritoneum, instead of the SCM muscle. In our study, four different groups, each consisting of 10 Wistar albino rats were used (Control group, sternocleidomastoid muscle group, liver group, peritoneum group). Parathyroidectomy was performed and the parathyroid tissue was seeded into the sternocloid mastoid muscle, liver and peritoneum. After 14 days, the rats were sacrificed and levels of calcium, magnesium, phosphorus, alkaline phosphatase and parathyroid hormone were measured in rats’ blood samples. The autotransplanted parathyroid tissue was then excised and examined. In all groups, parathyroid tissues were analyzed histopathologically according to calcification, necrosis, tissue loss, foreign body reaction, inflammation and fibrosis. Regarding Ca, Mg, PO4, ALP; There were no difference between the groups. When we compared control group with the other groups; a difference was observed in the levels of PTH (P<0.05). In pathological examination; regarding tissue loss; there was a difference between liver and peritoneum groups (P<0.05). In our study, we expected better result in plantings inside liver and peritone compared to SKM. However, there were no difference between the groups. PMID:26629152

  10. Imaging of the thyroid and parathyroid glands.

    PubMed

    Vazquez, Bianca J; Richards, Melanie L

    2011-02-01

    Current multimodal imaging techniques offer practicing providers the adequate framework to plan and accomplish care for patients with thyroid and parathyroid disorders. Available imaging modalities include ultrasonography (US), nuclear scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI). US remains the most cost-effective and the safest approach for the initial evaluation of the thyroid gland. Parathyroid subtraction scintigraphy provides localization of pathologic parathyroid glands with the greatest sensitivity. Localizing imaging studies allow for surgical planning with minimal risk and morbidity to the patient. CT scan and MRI play an adjunctive role in the further characterization of neck pathology. PMID:21184899

  11. Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics

    PubMed Central

    Abdelgadir Adam, Mohamed; Untch, Brian R.

    2010-01-01

    Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma. PMID:20051478

  12. Parathyroid cancer - difficult diagnosis - a case report.

    PubMed

    Pyzik, Aleksandra Joanna; Matyjaszek-Matuszek, Beata; Zwolak, Agnieszka; Chrapko, Beata; Pyzik, Dawid; Strawa-Zakościelna, Katarzyna

    2016-01-01

    Parathyroid cancer is a rare disorder of unclear etiology that is difficult to diagnose and treat. It is most often diagnosed incidentally based on multi-organ non-specific symptoms of hypercalcemia as a consequence of parathyroid hormone oversecretion. We present a case of a male with primary hyperparathyroidism who was diagnosed with parathyroid cancer ectopically located in the mediastinum only after the third surgery. However, due to chronic hypercalcemia, problems with localization and a bad clinical condition, the patient was not able to undergo a radical resection and one year after the first pathological fracture died. Taking into consideration the whole clinical picture we want to emphasize the need to apply comprehensive differential diagnosis of hypercalcemia and localization diagnosis of parathyroid tissue with a use of MIBI scintigraphy accompanied by the computed tomography and magnetic resonance imaging, as the most specific diagnostic tools employed in this pathology. PMID:26838944

  13. Robotic transaxillary and retroauricular parathyroid surgery

    PubMed Central

    Mohamed, Hossam Eldin; Bhatia, Parisha; Aslam, Rizwan; Moulthrop, Thomas

    2015-01-01

    Current advancement in robotic surgery has provided a safe, precise, 3-dimensional (3D) magnified dissection for parathyroid surgery without the need for CO2 insufflation, and with a better cosmetic outcome due to an invisible scar in the axillary or retroauricular region. Preoperative imaging studies that assist in the localization of lesions have been key elements in patients’ selection for targeted parathyroid surgery. PMID:26425455

  14. The management of 50 unusual hyperfunctioning parathyroid glands.

    PubMed

    Gaz, R D; Doubler, P B; Wang, C A

    1987-12-01

    From 1926 to 1984, 1200 patients with hyperparathyroidism were treated surgically at Massachusetts General Hospital (MGH). This series included 50 (4%) unusual cases that involved anomalous parathyroid locations or supernumerary hyperfunctioning parathyroid glands. In 42 cases the diseased glands were found in unusual locations: In three patients, glands were high in the neck behind the angle of the jaw; nine patients' glands were entirely encapsulated within the thyroid gland; and 30 patients required sternotomy for removal of mediastinal tumors. The eight remaining patients (as well as five of the mediastinal cases) had supernumerary hyperfunctioning glands. The three undescended parapharyngeal neoplasms, five of the cervical supernumerary tumors, and the majority of the mediastinal glands were associated with the thymus gland or thymic remnants. These glands appeared to arise from undescended parapharyngeal vestiges, partially descended parathymus remnants deposited along the path of developmental migration, or hyperdescended mediastinal inferior glands from branchial pouch III. The nine intrathyroid parathyroids were totally enclosed within the thyroid parenchyma. These appeared to arise from superior parathyroid glands that were trapped during fusion of the lateral wing portion from branchial pouch IV with the developing lateral lobes of the median thyroid primordium. Of these fifty cases, 39 patients had undergone a total of 60 previous operations (57 cervical and three mediastinal explorations) at MGH (16 patients) or other institutions (23 patients). In eleven patients the unusual hyperfunctioning gland was successfully identified at the time of the initial operation. Forty-four patients (88%) were surgically cured, as evidenced by eucalcemia. There were six patients with permanent hypoparathyroidism and none with persistent or recurrent hyperparathyroidism. PMID:3686358

  15. Defining the syndromes of parathyroid failure after total thyroidectomy

    PubMed Central

    Lorente-Poch, Leyre; Sancho, Juan J.; Muñoz-Nova, Jose Luis; Sánchez-Velázquez, Patricia

    2015-01-01

    Acute and chronic parathyroid insufficiency syndromes are the most common complication after total thyroidectomy. Permanent hypoparathyroidism imposes an important medical burden on patient lifestyle due to the need for lifetime medication, regular visits and significant long-term costs. Its true prevalence has been underestimated due to lack of clear definitions, inadequate follow-up and conflicts of interest when reporting individual patient series. The aim of this review is to propose precise definitions for the different syndromes associated to parathyroid failure based on the follow-up and management of patients developing hypocalcemia (<8 mg/dL at 24 hours) after first-time total thyroidectomy for cancer or goiter at our unit. Short and long-term post-thyroidectomy parathyroid failure presents as three different metabolic syndromes: (I) postoperative hypocalcemia is defined as a s-Ca <8 mg/dL (<2 mmol/L) within 24 hours after surgery requiring calcium/vit D replacement therapy at the time of hospital discharge; (II) protracted hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement at 4-6 weeks; and (III) permanent hypoparathyroidism as a subnormal iPTH concentration (<13 pg/mL) and/or need for calcium/vit D replacement 1 year after total thyroidectomy. Each of these syndromes has its own pattern of recovery and should be approached with different therapeutic strategies. PMID:25713783

  16. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia.

    PubMed Central

    Arnold, A; Brown, M F; Ureña, P; Gaz, R D; Sarfati, E; Drüeke, T B

    1995-01-01

    The pathogeneses of parathyroid disease in patients with uremia and nonfamilial primary parathyroid hyperplasia are poorly understood. Because of multigland involvement, it has been assumed that these common diseases predominantly involve polyclonal (non-neoplastic) cellular proliferations, but an overall assessment of their clonality has not been done. We examined the clonality of these hyperplastic parathyroid tumors using X-chromosome inactivation analysis with the M27 beta (DXS255) DNA polymorphism and by searching for monoclonal allelic losses at M27 beta and at loci on chromosome band 11q13. Fully 7 of 11 informative hemodialysis patients (64%) with uremic refractory hyperparathyroidism harbored at least one monoclonal parathyroid tumor (with a minimum of 12 of their 19 available glands being monoclonal). Tumor monoclonality was demonstrable in 6 of 16 informative patients (38%) with primary parathyroid hyperplasia. Histopathologic categories of nodular versus generalized hyperplasia were not useful predictors of clonal status. These observations indicate that monoclonal parathyroid neoplasms are common in patients with uremic refractory hyperparathyroidism and also develop in a substantial group of patients with sporadic primary parathyroid hyperplasia, thereby changing our concept of the pathogenesis of these diseases. Neoplastic transformation of preexisting polyclonal hyperplasia, apparently due in large part to genes not yet implicated in parathyroid tumorigenesis and possibly including a novel X-chromosome tumor suppressor gene, is likely to play a central role in these disorders. Images PMID:7738171

  17. 18F-FDG PET/CT Osteometabolic Activity in Metastatic Parathyroid Carcinoma.

    PubMed

    do Vale, Rômulo Hermeto Bueno; Queiroz, Marcelo Araújo; Coutinho, Artur Martins Novaes; Buchpiguel, Carlos Alberto; de Menezes, Marcos Roberto

    2016-09-01

    Parathyroid cancer is an uncommon type of malignancy, which is frequently associated with poor prognosis. Clinical manifestations are caused by elevated serum calcium and parathyroid hormone (PTH). Diagnostic imaging studies as neck ultrasonography, technetium Tc Tc-sestamibi whole body scintigraphy, CT, and MR are already established tools for this malignancy. Nevertheless, the role of F-FDG PET/CT remains unknown in this scenario, with few published studies in literature. Hence, in this article, we aimed to report an illustrative case of increased skeletal FDG uptake associated with high calcium and PTH levels. PMID:27276208

  18. Thyroid cancer incidence in simultaneous thyroidectomy with parathyroid surgery

    PubMed Central

    Emirikçi, Selman; Özçınar, Beyza; Öner, Gizem; Omarov, Nail; Ağcaoğlu, Orhan; Soytaş, Yiğit; Aksakal, Nihat; Yanar, Fatih; Barbaros, Umut; Erbil, Yeşim

    2015-01-01

    Objective: Primary hyperparathyroidism (PHPT) is often seen in conjunction with an underlying thyroid disorder. Imaging methods that are used to localize the parathyroid adenoma also detect associated thyroid nodules and thyroid cancer. The aim of this study was to detect the rate of thyroid cancer identified while performing parathyroidectomy and thyroidectomy in patients with PHPT. Material and Methods: Files of all patients who were operated for PHPT and who underwent simultaneous thyroidectomy were analyzed. Data regarding parathyroid pathology, surgical procedures, indications of thyroid surgery, and pathology results were retrospectively recorded. The indications for thyroid surgery included presence of suspicious thyroid nodules in ultrasonography, increase in size of thyroid nodules in follow-up ultrasound, or presence of suspicious thyroid fine needle aspiration biopsy (FNAB) findings. Rates of thyroid cancer detection were investigated according to definite pathology reports. Results: Eighty-three patients who underwent parathyroidectomy with a diagnosis of PHPT with concurrent thyroidectomy in Department of General Surgery, İstanbul University İstanbul Faculty of Medicine were included in the study. Eighteen patients were male (22%) and 65 were female (78%). The median age was 53 (18–70) years. The primary indication for parathyroidectomy was primary hyperparathyroidism in all patients. The thyroid procedures applied in addition to parathyroidectomy were lobectomy + isthmusectomy in 29 patients (35%), bilateral subtotal thyroidectomy in 20 patients (24%), bilateral total thyroidectomy in 23 patients (28%), and total thyroidectomy on one side and near total thyroidectomy to the other side in 11 patients (13%). The only indication for thyroidectomy was the presence of thyroid nodules until 2000 (20 patients, 24%). Indications in the remaining 63 patients included the presence of multiple nodules that cannot be followed up by ultrasonography in 25

  19. Xeno-Klotho Inhibits Parathyroid Hormone Signaling.

    PubMed

    Takenaka, Tsuneo; Inoue, Tsutomu; Miyazaki, Takashi; Hayashi, Matsuhiko; Suzuki, Hiromichi

    2016-02-01

    Although fibroblast growth factor (FGF) 23 was recently identified as a phosphatonin that influences vitamin D metabolism, the underlying signaling mechanisms remain unclear. FGF23 elevates the renal levels of membrane-associated klotho as well as soluble klotho. Klotho is expressed on distal tubules. Upon enzymatic cleavage, soluble klotho is released into the renal interstitial space and then into the systemic circulation. The expression of 25-hydroxyvitamin D3 1α-hydroxylase (1-OH) on proximal tubular cells is controlled by parathyroid hormone (PTH). Klotho binds to various membrane proteins to alter their function. Here, the interaction between the PTH receptor and klotho was studied using various approaches, including immunoprecipitation, in vitro cell culture, and in vivo animal experiments. Immunoprecipitation studies demonstrate, for the first time, that recombinant human klotho protein interacts with human PTH receptors to inhibit the binding of human PTH. Furthermore, when applied to human proximal tubular cells, recombinant human klotho suppresses PTH-stimulated generation of inositol trisphosphate in vitro. Moreover, PTH-induced increase of cyclic AMP secretion and 1α,25-dihydroxyvitamin D3 (1,25VD) was attenuated by recombinant human klotho in vivo. In addition, recombinant human klotho inhibits the expression of 1-OH by PTH both in vitro and in vivo. These results suggest that free klotho mediates the FGF23-induced inhibition of 1,25VD synthesis. © 2015 American Society for Bone and Mineral Research. PMID:26287968

  20. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    PubMed Central

    Underbjerg, Line; Sikjaer, Tanja

    2015-01-01

    Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy. PMID:26394728

  1. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone.

    PubMed

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2015-12-01

    Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy. PMID:26394728

  2. Multiple brown tumours from parathyroid carcinoma.

    PubMed

    Dagang, Daryl Jade Tardo; Gutierrez, Jerico Baliton; Sandoval, Mark Anthony Santiago; Lantion-Ang, Frances Lina

    2016-01-01

    We report a case of a 29-year-old woman who suffered from severe bilateral inguinal pain and left mandibular mass. CT scan showed innumerable expansile osteolytic bone masses on the iliac wings, femur, ribs and vertebral bodies, diffuse skeletal osteopaenia, calyceal lithiasis on the right kidney and a left thyroid mass. Ionised calcium and intact parathyroid hormone (PTH) were elevated. Parathyroid sestamibi scan showed a hyperfunctioning left inferior parathyroid gland. Biopsy of the left mandibular mass was consistent with brown tumour. The patient underwent parathyroidectomy of the enlarged parathyroid gland. Final histopathology, however, revealed parathyroid carcinoma, 4.7 cm in widest dimension, with capsular and vascular space invasion. The patient underwent repeat surgery, specifically, left thyroid lobectomy, isthmectomy and central node dissection. Intact PTH decreased from 681.3 to 74 pg/mL (normal range: 10-65) 24 hours postoperatively. Follow-up at 6 months showed normal serum calcium levels, size reduction of bone lesions and improvement of quality of life. PMID:27358103

  3. Parathyroid carcinoma presenting as normocalcemic hyperparathyroidism.

    PubMed

    Campennì, Alfredo; Ruggeri, Rosaria M; Sindoni, Alessandro; Giovinazzo, Salvatore; Calbo, Enrico; Ieni, Antonio; Calbo, Letterio; Tuccari, Giovanni; Baldari, Sergio; Benvenga, Salvatore

    2012-05-01

    Parathyroid carcinoma (PC) is a rare malignancy, with an indolent but progressive course. Long-term survival is largely dependent on the extent of the primary surgical resection. Hence, pre- or intraoperative suspicion of malignancy is of great importance. We describe the case of a 62-year-old woman with a 2-year history of asthenia and mental depression. Her past medical history was significant for osteoporosis. A diagnosis of primary normocalcemic hyperparathyroidism was established and the patient underwent surgery. PC was suspected intraoperatively because of the size and appearance of the parathyroid mass (a grayish, lobulated 3.5 cm mass). Thus, aggressive surgery (en bloc resection) was performed, along with bilateral neck exploration. Pathological examination of the specimens confirmed the suspicion of PC, demonstrating vascular invasion and extracapsular infiltration into adjacent soft tissue. Immunohistochemical staining revealed an elevated Ki-67 score (8.43%; cut-off value 5%). The mean area of silver-stained nucleolar organizer regions (AgNOR) was high (4.972 μm(2)), indicating an elevated proliferation rate. Serum calcium and parathyroid hormone levels normalized postoperatively, and the patient's 5-year outcome was good. The present case provides evidence that parathyroid malignancy cannot be excluded a priori based on normocalcemic hyperparathyroidism, emphasizing the variability in clinical presentation. Moreover, Ki-67 expression and AgNOR analysis confirmed their additional value in complementing the histological evaluation of a parathyroid malignant mass. PMID:22246083

  4. Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis.

    PubMed

    Kamali, D; Sharpe, A; Nagarajan, S; Elsaify, W

    2016-07-01

    Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy. PMID:27055408

  5. Determining Directional Dependency in Causal Associations

    ERIC Educational Resources Information Center

    Pornprasertmanit, Sunthud; Little, Todd D.

    2012-01-01

    Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…

  6. Parathyroid adenoma imaged by gallium-67 citrate. A case report

    SciTech Connect

    Katagiri, M.; Harada, T.; Kawano, R.; Okamura, Y.; Miyake, K.; Otsuka, N.; Fukunaga, M.; Morita, R.

    1987-10-01

    A parathyroid adenoma imaged by Ga-67 citrate in a 17-year-old man with primary hyperparathyroidism and a palpable solid tumor in the neck is presented. Although preoperative examination and intraoperative findings suggested a parathyroid carcinoma, histologic studies showed a parathyroid adenoma with predominant chief cell type.

  7. Diagnosis of parathyroid carcinoma using immunohistochemical staining against hTERT.

    PubMed

    Osawa, Naoshi; Onoda, Naoyoshi; Kawajiri, Hidemi; Tezuka, Kenji; Takashima, Tsutomu; Ishikawa, Tetsuro; Miyauchi, Akira; Hirokawa, Mitsuyoshi; Wakasa, Kenichi; Hirakawa, Kosei

    2009-12-01

    The differential diagnosis of parathyroid carcinoma from benign adenoma is often difficult when its typical clinicopathological features are absent, even with the aid of various molecular markers. We recently demonstrated that telomerase activation through hTERT expression is a unique characteristic that is limited to parathyroid carcinoma and not seen in benign tumors. In the present study, we investigated hTERT expression in parathyroid tumors using immunohistochemistry in an attempt to determine its clinical utility. There was no evidence of immunoreactivity in the 4 normal parathyroid glands and the 18 typical adenomas. In contrast, one atypical adenoma stained positively and homogeneously, and the disease recurred three times clinically. All of the 6 carcinomas demonstrated a clear positive nuclear staining of hTERT. Every hTERT-positive tumor showed a high Ki-67 index, i.e., greater than 4%. Nucleolin, an hTERT-binding protein, was abundantly and homogeneously expressed in all specimens examined independent of the pathological diagnosis and hTERT or Ki-67 expression. Therefore, it is possible that immunostaining with an anti-hTERT antigen (NCL-L-hTERT) individually may distinguish parathyroid carcinoma from benign tumors. PMID:19885612

  8. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients.

    PubMed

    Komaba, Hirotaka; Goto, Shunsuke; Fujii, Hideki; Hamada, Yasuhiro; Kobayashi, Akira; Shibuya, Koji; Tominaga, Yoshihiro; Otsuki, Naoki; Nibu, Ken-Ichi; Nakagawa, Kimie; Tsugawa, Naoko; Okano, Toshio; Kitazawa, Riko; Fukagawa, Masafumi; Kita, Tomoyuki

    2010-02-01

    Fibroblast growth factor 23 (FGF23) exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho. Parathyroid glands express both FGFR1 and Klotho, and FGF23 decreases parathyroid hormone gene expression and hormone secretion directly. In uremic patients with secondary hyperparathyroidism (SHPT), however, parathyroid hormone secretion remains elevated despite extremely high FGF23 levels. To determine the mechanism of this resistance, we measured the expression of Klotho, FGFR1, and the proliferative marker Ki67 in 7 normal and 80 hyperplastic parathyroid glands from uremic patients by immunohistochemistry. All uremic patients had severe SHPT along with markedly high FGF23 levels. Quantitative real-time reverse transcription PCR showed that the mRNA levels for Klotho and FGFR1correlated significantly with their semi-quantitative immunohistochemical intensity. Compared with normal tissue, the immunohistochemical expression of Klotho and FGFR1 decreased, but Ki67 expression increased significantly in hyperplastic parathyroid glands, particularly in glands with nodular hyperplasia. These results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients. PMID:19890272

  9. Parathyroid Hormone, Calcitonin, and Vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T.

    1972-01-01

    Analyses of secretion of parathyroid hormone during tests of stimulation and suppression of hormone-secretory activity using infusions of EDTA and calcium, respectively, have established that, in contrast to previous views, secretion of the hormone is not autonomous in many patients that have adenomatous hyperparathyroidism, but is responsive to changes in blood-calcium concentration. These findings have led to a new understanding of the pathophysiology of hormone production in hyperparathy-roidism. A related application of the diagnostic use of the radioimmunoassay is the preoperative localization of parathyroid tumors and the distinction between adenomas and chief-cell hyperplasia. Work involving catheterization and radioimmunoassay of blood samples obtained from the subclavin and innominate veins and the venae cavae, led to localization in a high percentage of patients. However, this procedure has been adopted recently to detect hormone concentration in the small veins directly draining the parathyroid glands.

  10. Parathyroid adenocarcinoma in a nephropathic Persian cat.

    PubMed

    Cavana, Paola; Vittone, Valentina; Capucchio, Maria T; Farca, Anna M

    2006-10-01

    This report describes an uncommon clinical case of cystic parathyroid adenocarcinoma. A 17-year-old male Persian cat was presented for evaluation of a ventral cervical mass. The cat was inappetent and showed weight loss, polydipsia and vomiting. Serum biochemistry and urinalysis revealed moderate hypercalcaemia, a mild increase of creatinine, isosthenuria and proteinuria. Sodium dodecyl sulphate-agarose gel electrophoresis showed a mixed tubular proteinuric pattern, in accordance with histological examination that revealed interstitial nephritis and glomerulonephritis. Diagnosis of parathyroid carcinoma was based on histopathological findings. PMID:16651017

  11. The reptilian thyroid and parathyroid glands.

    PubMed

    Rivera, Sam; Lock, Brad

    2008-01-01

    The field of reptilian clinical endocrinology is still in its infancy. The thyroid and parathyroid glands are intimately involved with many basic metabolic functions. These glands have been the subject of extensive research studies in reptilian species; however, the effects of abnormal gland function have been poorly documented in clinical cases. These glands play a major role in maintaining physiologic homeostasis in all vertebrates. With the advent of more sensitive assays, it should be possible to measure the small amounts of hormones found in reptilian species. The purpose of this article is to review the literature regarding clinical endocrinology of the thyroid and parathyroid glands in reptiles. PMID:18165144

  12. Hypercalcaemia due to parathyroid carcinoma presenting in the third trimester of pregnancy.

    PubMed

    Paul, Ryan G; Elston, Marianne S; Gill, Anthony J; Marsh, Deborah; Beer, Ian; Wolmarans, Louise; Conaglen, John V; Meyer-Rochow, Goswin Y

    2012-04-01

    Primary hyperparathyroidism (pHPT) in pregnancy may be associated with significant maternal and fetal morbidity and mortality. Medical management of pHPT in pregnancy is limited, and surgery is the only definitive therapeutic option. The ideal timing for surgery is mid-second trimester, but surgery may also be safely performed in the third trimester. Delayed parathyroid surgery may result in a hypercalcaemic crisis postpartum owing to loss of active placental calcium transfer. We present a case of parathyroid carcinoma in pregnancy presenting with pre-eclampsia at 32 weeks' gestation. PMID:22188427

  13. Water-clear cell parathyroid adenoma causing primary hyperparathyroidism in a patient with neurofibromatosis type 1: report of a case.

    PubMed

    Kodama, Hitomi; Iihara, Masatoshi; Okamoto, Takahiro; Obara, Takao

    2007-01-01

    Water-clear cell parathyroid adenoma is an exceedingly rare tumor, composed exclusively of tumor cells with abundant foamy cytoplasm. A combination of hyperparathyroidism and neurofibromatosis type 1 (NF1) is also a rare phenomenon. We report an 18-year-old woman with primary hyperparathyroidism caused by water-clear cell parathyroid adenoma in association with NF1. She had renal stones, hypercalcemia, and an elevated plasma level of intact parathyroid hormone. Physical examination revealed a palpable tumor in the right neck, and café-au-lait spots distributed over her entire body. An ultrasound examination showed an isoechoic mass in the right thyroid lobe. Thallium-technetium subtraction scintigraphy showed high thallium accumulation in the right thyroid lobe area. A surgical exploration revealed the palpable mass to be a parathyroid tumor. The pathological features were consistent with water-clear parathyroid adenoma. This is the first reported case of water-clear cell parathyroid adenoma associated with NF1. PMID:17879040

  14. An Unusual Neck Mass: A Case of a Parathyroid Cyst and Review of the Literature

    PubMed Central

    Goomany, Anand; Rafferty, Amy; Smith, Ian

    2015-01-01

    Parathyroid cysts (PC) are an unusual cause of neck swellings. The majority are nonfunctioning and prove to be a diagnostic challenge given their nonspecific physical and radiological characteristics. This is compounded by their rare occurrence, leading them to be overlooked in the differential diagnosis of neck lumps. Imaging techniques fail to determine the origin of these lesions, but a preoperative diagnosis can be achieved by fine-needle aspiration and measurement of cystic fluid C-terminal parathyroid hormone levels. Treatment of nonfunctioning cysts remains controversial and includes needle aspiration, injection of sclerosant, or surgical excision. We present a case of a 44-year-old female presenting with an asymptomatic anterior neck swelling, diagnosed postoperatively as a parathyroid cyst. PMID:26064758

  15. Increased protein kinase A type Iα regulatory subunit expression in parathyroid gland adenomas of patients with primary hyperparathyroidism.

    PubMed

    Hibi, Yatsuka; Kambe, Fukushi; Imai, Tsuneo; Ogawa, Kimio; Shimizu, Yoshimi; Shibata, Masahiro; Kagawa, Chikara; Mizuno, Yutaka; Ito, Asako; Iwase, Katsumi

    2013-01-01

    Protein kinase A (PKA) regulatory subunit type Iα (RIα) is a major regulatory subunit that functions as an inhibitor of PKA kinase activity. We have previously demonstrated that elevated RIα expression is associated with diffuse-to-nodular transformation of hyperplasia in parathyroid glands of renal hyperparathyroidism. The aim of the current study was to determine whether or not RIα expression is increased in adenomas of primary hyperparathyroidism (PHPT), because monoclonal proliferation has been demonstrated in both adenomas and nodular hyperplasia. Surgical specimens comprising 22 adenomas and 11 normal glands, obtained from 22 patients with PHPT, were analyzed. Western blot and immunohistochemical analyses were employed to evaluate RIα expression. PKA activities were determined in several adenomas highly expressing RIα. RIα expression was also separately evaluated in chief and oxyphilic cells using the "Allred score" system. Expression of proliferating cell nuclear antigen (PCNA), a proliferation marker, was also immunohistochemically examined. Western blot analysis revealed that 5 out of 8 adenomas highly expressed RIα, compared with normal glands. PKA activity in adenomas was significantly less than in normal glands. Immunohistochemical analysis further demonstrated high expression of RIα in 20 out of 22 adenomas. In adenomas, the greater RIα expression and more PCNA positive cells were observed in both chief and oxyphilic cells. The present study suggested that high RIα expression could contribute to monoclonal proliferation of parathyroid cells by impairing the cAMP/PKA signaling pathway. PMID:23197043

  16. In experimental chronic kidney disease or cancer, parathyroid hormone is a novel mediator of cachexia.

    PubMed

    Wyatt, Christina M; Mitch, William E

    2016-05-01

    Hyperparathyroidism plays a central role in the disordered bone mineral metabolism of chronic kidney disease, and has been associated with increased cardiovascular morbidity and mortality in that setting. A recent study suggests a novel role for parathyroid hormone and its receptor in muscle wasting and cachexia occurring in advanced chronic kidney disease. PMID:27083271

  17. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    PubMed

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2015-09-01

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here. PMID:25227285

  18. Imaging of the parathyroid glands in primary hyperparathyroidism.

    PubMed

    Minisola, Salvatore; Cipriani, Cristiana; Diacinti, Daniele; Tartaglia, Francesco; Scillitani, Alfredo; Pepe, Jessica; Scott-Coombes, David

    2016-01-01

    Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases worldwide. Surgery is the only potentially curable option for patients with this disorder, even though in asymptomatic patients 50 years of age or older without end organ complications, a conservative treatment may be a possible alternative. Bilateral neck exploration under general anaesthesia has been the standard for the definitive treatment. However, significant improvements in preoperative imaging, together with the implementation of rapid parathyroid hormone determination, have determined an increased implementation of focused, minimally invasive surgical approach. Surgeons prefer to have a localization study before an operation (both in the classical scenario and in the minimally invasive procedure). They are not satisfied by having been referred a patient with just a biochemical diagnosis of PHPT. Imaging studies must not be utilized to make the diagnosis of PHPT. They should be obtained to both assist in determining disease etiology and to guide operative procedures together with the nuclear medicine doctor and, most importantly, with the surgeon. On the contrary, apart from minimally invasive procedures in which localization procedures are an obligate choice, some surgeons believe that literature on parathyroidectomy over the past two decades reveals a bias towards localization. Therefore, surgical expertise is more important than the search for abnormal parathyroid glands. PMID:26340967

  19. Technical Factors Involved in Parathyroid Surgery.

    PubMed

    Dumitras, M; Strambu, V; Radu, P A; Iorga, C; Bengulescu, I; Popa, F

    2015-01-01

    We aimed to investigate the frequency of ectopic and supernumerary parathyroid glands in our series of renal hyperparathyroidism. From October 2011 to November 2014, 202 patients with chronic renal failure and advanced SHPT nonresponsive to medical therapy were hospitalized in the General Surgery Department of the Carol Davila Nephrology Hospital. These patients underwent a number of 188 (93%) total parathyroidectomies and a number of 14 patients (7%) subtotal parathyroidectomies. Of these 202 patients, reoperation was carried out for 14 patients (7%) in which we identified ectopic and supernumerary parathyroid glands. Operative details and pathology results were prospectively collected and reviewed after we obtained informed consent for data and pictures use. In 188 patients (93% cases), four or more parathyroid glands were removed at the first operation. In 14 cases (7%) high PTH level persisted after the initial operation. In 22 of them (11%), supernumerary glands were found at the first operation and in 6 of them (3%) at the second operation. We conclude that extensive cervical exploration in addition with preoperative imaging tests, parathyroid ultrasound; scintigraphy with Tc will reduce secondary hyperparathyroidism surgery. PMID:26531785

  20. Parathyroid adenoma upstaging the lung cancer.

    PubMed

    Okuyucu, Kursat; Kavakli, Kuthan; Ozaydın, Sukru; Karahatay, Serdar; Karatas, Okan; Doğan, Deniz

    2015-05-01

    Mediastinal staging of NSCLC with noninvasive methods such as PET/CT can be misleading when a mediastinal disease accompany. Histopathologic confirmation should be made before any treatment plan. Herein, we presented a case of parathyroid adenoma upstaging the lung cancer. PMID:25618011

  1. Parathyroid carcinoma: Challenges in diagnosis and treatment.

    PubMed

    Betea, Daniela; Potorac, Iulia; Beckers, Albert

    2015-05-01

    Parathyroid carcinoma is a malignant neoplasm affecting 0.5 to 5.0% of all patients suffering from primary hyperparathyroidism. This cancer continues to cause challenges for diagnosis and treatment because of its rarity, overlapping features with benign parathyroid disease, and lack of distinct characteristics. The third/second generation PTH assay ratio provides valuable information to distinguish between benign parathyroid disease and parathyroid carcinoma. An abnormal ratio (>1) could indicate a high suspicion regarding carcinoma and metastatic disease. Early en bloc surgical resection of the primary tumour with clear margins remains the best curative treatment. Although prolonged survival is possible with recurrent or metastatic disease, cure is rarely achievable. The efficacy of classical adjuvant therapies, such as radiotherapy and chemotherapy, in management of persistent, recurrent, or metastatic disease has been disappointing. In metastatic disease the goal of therapeutic support is to control the PTH-driven hypercalcemia that represents the primary cause of mortality. Calcimimetics, which are allosteric modulators of the calcium sensing receptor, have a sustained effect in lowering serum calcium levels. Bone anti-resorptive therapy, like intravenous bisphosphonates (pamidronate and zolendronate), or more recently denosumab (fully human monoclonal antibody with high affinity to bind RANK ligand) might be temporarily useful. In a small number of cases treated with anti-PTH immunotherapy, inducing anti-PTH antibodies, promising results have been seen with clinical improvements and decrease of calcemia. In one case metastasis shrinkage has been observed. PMID:25910997

  2. Intraoperative Parathyroid Hormone Monitoring Corroborates the Success of Parathyroidectomy in Children

    PubMed Central

    Çelik, Ahmet; Divarcı, Emre; Dökümcü, Zafer; Ergün, Orkan; Özen, Samim; Gökşen, Damla; Darcan, Şükran; Ertan, Yeşim

    2014-01-01

    Ob­jec­ti­ve: To assess the efficacy of intraoperative parathyroid hormone (PTH) monitoring in evaluating the outcome of parathyroidectomy in pediatric patients. Methods: Intraoperative PTH monitoring during parathyroidectomy was performed in five children (3M, 2F); three had parathyroid adenomas (single gland disease) and two had primary hyperplasia. One patient had undergone two previous surgical interventions to remove the parathyroid glands, but the PTH levels had remained high with persistence of symptoms. Immunoradiometric analysis was used for PTH measurements. Preoperative PTH values were obtained to monitor the baseline levels. Serum samples were collected 20 minutes after removal of the adenoma/parathyroid gland(s) and PTH levels were compared with preoperative values. Specimens were also confirmed by frozen sectional examination. Results: Mean age of the patients was 11 years (range: 3 months-16 years). Mean preoperative PTH values were 633.3±579 pg/mL (range: 143-1300 pg/mL). Intraoperative values decreased to 18.7±5.5 pg/mL (range: 8-27 pg/mL) following removal of the gland(s). Normal calcium levels were achieved with adequate management following surgery. One patient (with multiple surgeries and found to have an ectopic parathyroid gland) had hungry bone syndrome after the operation and was treated successfully. There were no major complications. All patients maintained normal calcium/phosphorus levels in the follow-up period, ranging from 2 to 5 years. Conclusion: An ectopic parathyroid gland or another undetected adenoma can be overlooked during surgery. Owing to the short life of the hormone, intraoperative PTH monitoring to determine PTH clearance proved to be a feasible marker for adequacy and safety of surgery and “cure”. PMID:25241609

  3. Effect of Occupational Cadmium Exposure on Parathyroid Gland

    PubMed Central

    Ibrahim, Khadiga S.; Beshir, Safia; Shahy, Eman M.; Shaheen, Weam

    2016-01-01

    BACKGROUND: Cadmium (Cd) is used in many industries. High-level exposure is associated with severe kidney and bone damage. AIM: This study investigates the possible effect of occupational cadmium exposure on parathyroid gland and some minerals in workers. METHODS: Environmental air monitoring of cadmium was done. Serum and urine cadmium levels, kidney function, some minerals, and plasma parathormone were estimated in the studied groups. RESULTS: The exposed workers had significantly higher Cd concentration in serum and urine than controls. The mean levels of plasma parathyroid hormone, serum phosphorus and magnesium were significantly lower among the exposed group. However, the mean levels of serum creatinine and calcium were significantly higher in the same group when compared to referents. There was a significant positive correlation between Cd concentration in the serum and urine for the exposed group. The biological Cd exposure indices correlated positively with serum calcium and negatively with plasma PTH level. The prevalence of musculoskeletal complaints, bone ache, joint pain and muscle spasm were more prevalent among the exposed workers compared with the controls with odds ratio 4.316, 3.053 and 3.103 respectively. CONCLUSIONS: Occupational cadmium exposure has an adverse effect on PTH level and serum human minerals. PMID:27335606

  4. Clinicopathological phenotype of parathyroid carcinoma: therapeutic and prognostic aftermaths.

    PubMed

    Diaconescu, M R; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

    2015-01-01

    Parathyroid carcinomas (PC) are rare and "devastating"€ causes of hyperparathyroidism (HP), frequently discovered fortuitously,with not always doubtless pathological confirmation, and dissociate post-therapeutic outcomes and prognosis even after well-performed surgery. We herein report four PT neoplasms,three of them proving to be authentic PCs, and one an atypical parathyroid adenoma. There were three females and one male, aged 32-49 (mean 44) years. In three circumstances PC was associated with primary HP and in one case the tumor had developed on a CKD-BMD (renal HP) background. All patients presented marked clinical and biochemical phenomena related to hypercalcemia with greater intensity of renal, bone, neuromuscular and psychological signs and symptoms to which in one observation specific uremic manifestations were added. Preoperative and intraoperative diagnosis was suspected only in two cases (one of them being in fact an atypical PT adenoma), but in the other two it was established by paraffin section on histological evidence of definitive stigma of malignancy. Our little experience underlines the wide and protean range of the origins, clinical aspects, course and prognosis of PC, which adds to the difficulties of pre- and intraoperative diagnosis. Awareness of this lesion must be permanent to detect its presence in any unusual eventuality, imposing a radical en bloc resection at the initial operation, assuring the best chance of cure. PMID:25800319

  5. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

    PubMed

    Gowen, M; Stroup, G B; Dodds, R A; James, I E; Votta, B J; Smith, B R; Bhatnagar, P K; Lago, A M; Callahan, J F; DelMar, E G; Miller, M A; Nemeth, E F; Fox, J

    2000-06-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  6. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    PubMed Central

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17β-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  7. Gallbladder adenocarcinoma and paraneoplastic parathyroid hormone mediated hypercalcemia

    PubMed Central

    Yogarajah, Meera; Sivasambu, Bhradeev; Shiferaw-Deribe, Zewge

    2016-01-01

    Parathyroid hormone mediated hypercalcemia is not always exclusively primary hyperparathyroidism and rarely could be due to ectopic parathyroid hormone secretion from tumor cells. We present a case of 86-year-old female with metastatic gall bladder adenocarcinoma diagnosed eight months back who presented with generalized fatigue and poor oral intake and was found to be hypercalcemic with elevated parathyroid hormone levels. Imaging with technetium 99 m sestamibi scintigraphy with dual phase, subtraction thyroid scan (dual isotope scintigraphy), magnetic resonance imaging and ultrasonography did not demonstrate any parathyroid lesion in normal or ectopic sites. We believe that the tumor cells were the source of ectopic parathyroid hormone secretion as we had excluded all the other possibilities with extensive combined imaging thereby increasing the sensitivity of our testing. We report the first case of metastatic gall bladder adenocarcinoma with paraneoplastic ectopic parathyroid hormone secretion. PMID:27081650

  8. Gallbladder adenocarcinoma and paraneoplastic parathyroid hormone mediated hypercalcemia.

    PubMed

    Yogarajah, Meera; Sivasambu, Bhradeev; Shiferaw-Deribe, Zewge

    2016-04-10

    Parathyroid hormone mediated hypercalcemia is not always exclusively primary hyperparathyroidism and rarely could be due to ectopic parathyroid hormone secretion from tumor cells. We present a case of 86-year-old female with metastatic gall bladder adenocarcinoma diagnosed eight months back who presented with generalized fatigue and poor oral intake and was found to be hypercalcemic with elevated parathyroid hormone levels. Imaging with technetium 99 m sestamibi scintigraphy with dual phase, subtraction thyroid scan (dual isotope scintigraphy), magnetic resonance imaging and ultrasonography did not demonstrate any parathyroid lesion in normal or ectopic sites. We believe that the tumor cells were the source of ectopic parathyroid hormone secretion as we had excluded all the other possibilities with extensive combined imaging thereby increasing the sensitivity of our testing. We report the first case of metastatic gall bladder adenocarcinoma with paraneoplastic ectopic parathyroid hormone secretion. PMID:27081650

  9. Hyperparathyroidism caused by a functional parathyroid cyst.

    PubMed

    Suzuki, Kunihiro; Sakuta, Ayuko; Aoki, Chie; Aso, Yosimasa

    2013-01-01

    A 67-year-old Japanese woman was admitted to our hospital for malaise and loss of appetite. Relevant biochemical examinations showed definite hypercalcaemia and elevated serum levels of intact parathyroid hormone (PTH). We performed thyroid ultrasonography and CT of the neck, which revealed a cystic lesion in the right lower lobe of the thyroid glands. Ultrasound-guided fine-needle aspiration was performed, and PTH level of the cystic fluid was markedly elevated. Technetium-99m-hexakis 2-methoxyisobutyi isonitrile sesta scintigraphy showed intense ring-shaped accumulation of radioactivity in the wall of the cyst. The patient underwent a right lobectomy to resect the cystic parathyroid adenoma. After surgery, her serum calcium and PTH level returned to normal ranges. PMID:23813580

  10. Parathyroid lesions: Difficult diagnosis on cytology.

    PubMed

    Agarwal, Charu; Kaushal, Manju

    2016-08-01

    Cytology of parathyroid lesion (PL) is often confused with that of thyroid lesions. Differentiation between thyroid and PL is very difficult on cytomorphology because of their similar features and close anatomical proximity. Three cases of PLs reported on cytology in last one year were retrieved from archives of cytology department. Their cytomorphological details were studied and were correlated with the available biochemical parameters. Histopathology was available in two cases. Radiological assistance and parathyroid hormone (PTH) assessment in our cases formed the basis of diagnosing PLs on cytology. We discuss the differential diagnosis and pitfalls in cytological diagnosis of PLs. However, histopathology remains the gold standard for diagnosis. Interpretation of PLs on cytology remains problematic due to its rarity and limited available literature. The cytomorphology combined with clinical and biochemical data supported by histopathology are necessary to improve the diagnostic sensitivity of PLs. Diagn. Cytopathol. 2016;44:704-709. © 2016 Wiley Periodicals, Inc. PMID:27246113

  11. Radiographic findings in recurrent parathyroid carcinoma

    SciTech Connect

    Krudy, A.G.; Doppman, J.L.; Marx, S.J.; Brennan, M.F.; Spiegel, A.; Aurback, G.D.

    1982-03-01

    Seven cases of recurrent parathyroid carcinoma were reviewed. Subperiosteal resorption was seen in 6, pulmonary nodules in 4, renal calculi in 5, brown tumors in 5, and pancreatic calcifications in 1. Angiography was performed in 5 patients, showing 1 definite and 2 probable cervical recurrences, 1 mediastinal lesion, and 1 case of possible bone metastases. Venous sampling for parathyroid hormone was carried out in 4 patients and suggested residual disease in 2; in addition, there were 1 false and 1 true negative. CT was performed in 4 patients and was useful in delineating metastatic pulmonary nodules, cervical recurrence, and hepatic metastases. The radiographic approach to recurrent parathryoid carcinoma and the use of CT and angiography are discussed.

  12. Cervical SPECT Camera for Parathyroid Imaging

    SciTech Connect

    None, None

    2012-08-31

    Primary hyperparathyroidism characterized by one or more enlarged parathyroid glands has become one of the most common endocrine diseases in the world affecting about 1 per 1000 in the United States. Standard treatment is highly invasive exploratory neck surgery called Parathyroidectomy. The surgery has a notable mortality rate because of the close proximity to vital structures. The move to minimally invasive parathyroidectomy is hampered by the lack of high resolution pre-surgical imaging techniques that can accurately localize the parathyroid with respect to surrounding structures. We propose to develop a dedicated ultra-high resolution (~ 1 mm) and high sensitivity (10x conventional camera) cervical scintigraphic imaging device. It will be based on a multiple pinhole-camera SPECT system comprising a novel solid state CZT detector that offers the required performance. The overall system will be configured to fit around the neck and comfortably image a patient.

  13. Original technique for preoperative preparation of patients and intraoperative localization of parathyroid adenomas

    PubMed Central

    PASTA, V.; MONTELEONE, F.; DEL VECCHIO, L.; IACOBELLI, S.; URCIUOLI, P.; D’ORAZI, V.

    2015-01-01

    Surgical approach of single parathyroid adenoma treatment is turning to a less invasive surgery, allowing us to obtain better aesthetic results, reduction of duration of surgical operation, reduction of post-operative morbidity and hospital stay. Tc99m-sestaMIBI scintigraphy is mainly performed for preoperative localization of parathyroid adenomas. Our technique is instead based on the possibility to inhibit the interference of Tc99m-sestaMIBI uptake of the thyroid gland by means of the administration of Lugol’s solution. Indeed, to confirm the identification and removal of the hyperfunctional parathyroid, it is accepted as adequate an ex vivo radioactivity count of the adenoma 20% or 40% greater than the value of the post-excisional background radioactivity, in association or not with intraoperative measurement of PTH. This method allows us to perform surgery with no timetable restriction, and to clearly distinguish the radioactivity of parathyroid adenoma from that of the surrounding tissues and thyroid gland. PMID:26188752

  14. Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas.

    PubMed

    Juhlin, C Christofer; Nilsson, Inga-Lena; Johansson, Kenth; Haglund, Felix; Villablanca, Andrea; Höög, Anders; Larsson, Catharina

    2010-09-01

    The identification of parathyroid carcinomas is based upon histopathological criteria in which an invasive growth pattern or distant metastasis is demonstrated. A dilemma arises when tumours present with atypical histopathological features but lack direct evidence of malignancy. Recently, reduced expression or loss of the tumour suppressor proteins parafibromin and adenomatous polyposis coli (APC) has been associated with parathyroid malignancy. We report results from APC and parafibromin expression analyses by immunohistochemistry and Western blot in five cases of atypical adenoma, a single case of carcinoma and 54 adenomas without atypical features. Complete loss of APC immunoreactivity and reduced expression of parafibromin was evident in two of the atypical adenomas and in the parathyroid carcinoma. By contrast, all adenomas displayed APC expression, including two cases with hyperparathyroidism 2 gene (HRPT2) mutations and loss of parafibromin expression. We conclude that loss of APC is a frequent molecular event in atypical adenomas and carcinomas, but not in adenomas. Following verification in an independent material, APC could become a valuable tool when assessing parathyroid tumours in the clinical setting. Furthermore, the molecular resemblance of atypical adenomas with carcinoma concerning parafibromin and APC expression indicates that atypical adenomas should be subjects to watchful follow-up. PMID:20473645

  15. Giant mediastinal parathyroid adenoma: a case report.

    PubMed

    Costanzo, Mario; Terminella, Alberto; Marziani, Alessia; Chisari, Antonio; Missiato, Alfredo; Cannizzaro, Matteo Angelo

    2009-01-01

    A 65 year old female patient suffering from multinodular goitre and from hypercalcaemic syndrome which had been and was being treated with drugs for a number of years. The patient undergoes total thyroidectomy. Surgical neck and anterior mediastinum exploration was negative for sick parathyroids. Neck and chest TC and 'TC sestamibi scintigraphy showed the presence of a 7 cm hyperfunctional ectopic parathyroid tissue in the postero-superior mediastinum infiltrating oesophagus. Video bronchoscopy revealed an extrinsic compression of the trachea. The patient underwent surgery. Through right postero-lateral thoracotomy and mediastinal pleura incision, the adenoma excision was carried out. The histological examination revealed a potentially malignant parathyroid adenoma with infiltration, without over-reaching the capsule. The surgical treatment resulted in an immediate resolution of the clinical symptomatology. One year later, the follow up was shown no observable relapse with normal calcium and PTH values. Today, the tendency to minimally invasive surgery, an accurate preoperative localization of the adenoma and the use of techniques such as intra-surgical nuclear mapping through manual gamma probes, selective angiography, venous intraoperative dosage of PTH and intra-surgical ultrasound scan. PMID:19537125

  16. Thallium-technetium parathyroid scan. A useful noninvasive technique for localization of abnormal parathyroid tissue

    SciTech Connect

    Manni, A.; Basarab, R.M.; Plourde, P.V.; Koivunen, D.; Harrison, T.S.; Santen, R.J.

    1986-06-01

    We studied the usefulness of the thallium-technetium scan in 60 patients with suspected parathyroid disorders. The scan correctly localized abnormal parathyroid tissue in 82% of patients with surgically proved primary hyperparathyroidism due to a single adenoma and in 60% of patients operated on for primary hyperplasia. The scan was particularly useful in patients who had undergone previous neck explorations, since it successfully identified residual adenomatous or hyperplastic tissue in six of seven patients. False-positive images were consistently produced in all patients with coexisting thyroid disease. We conclude that the thallium-technetium scan is useful for localizing abnormal parathyroid tissue. We recommend its routine use in patients with persistent or recurrent hypercalcemia following neck exploration for primary hyperparathyroidism who have no evidence of thyroid disorders.

  17. A rare cystic lesion of the neck: parathyroid cyst.

    PubMed

    Kaplanoglu, Veysel; Kaplanoglu, Hatice; Cılız, Deniz Sözmen; Duran, Semra

    2013-01-01

    Parathyroid cysts are rarely observed neck masses. Their physical examination is not specific and preoperative diagnosis is usually difficult. Imaging findings and ultrasound-guided fine-needle aspiration with hormone analysis evaluation are important diagnostic criteria. A 48-year-old female patient admitted to our hospital with a symptom of swelling on the left side of the neck was diagnosed with parathyroid cyst by imaging methods (ultrasonography, MRI, parathyroid scintigraphy) and laboratory findings. Fine-needle aspiration biopsy was performed and because of relapse on the follow-up sclerotherapy was planned. Our aim in this study was to present the radiological findings of this case of parathyroid cyst. PMID:24121814

  18. Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor

    SciTech Connect

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W.M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.

    2009-08-18

    Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1-108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an {alpha}-helical structure extending from residues 14-29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor.

  19. Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor*

    PubMed Central

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W. M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.

    2009-01-01

    Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1–108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an α-helical structure extending from residues 14–29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor. PMID:19346515

  20. Parathyroid scans and thyroid uptake of thallium 201 of subjects in chronic hemodialysis

    SciTech Connect

    Maayan, M.L.; Rubin, J.E.; Berlyne, G.; Volpert, E.M.; Sellitto, R.; Schor, S.; Braunstein, D.; Johnson, R.; Wallace, E.Z.; Bitton, R.N.

    1984-01-01

    Patients in chronic hemodialysis were injected i.v. 1mCi each Thallium Chloride 201 (TlCl) and Technetium 99m pertechnetate (Tc99m) and imagings of the thyroid and parathyroid glands were taken after 30, 60 and 90'. Parathyroid scans were obtained by computerized subtraction of the Tc99m from the TlCl image. The percentage uptake of TlCl and Tc99m was measured at 1 and 3 hrs in normal, hemodialyzed and thyroxine treated subjects as well as in untreated and thyroxine treated mice. Thyroid tests and serum electrolytes were routinely determined. Enlarged parathyroid glands were visualized in 5 out of 6 patients on hemodialysis. TlCl uptake was greatly decreased and thyroid imagings poor in patients in renal failure. This was parallel in all cases with a high serum K/sup +/. Tc99m uptake and scans were unaffected by renal status. Administration of L-thyroxine greatly reduced the thyroidal uptake and accompanying scans after both Tc99m and TlCl in human subjects as well as in experimental animals. The authors conclude the following: a) TlCl - Tc99m subtraction scans enabled visualization of hyperplastic parathyroid glands in patients in chronic hemodialysis; b) Thyroid uptake of TlCl was inversely related to the serum K/sup +/ level; and c) Both Tc99m and TlCl thyroidal uptake were inhibited by administration of L-thyroxine, hence TSH dependent.

  1. Parathyroid Hormone Replacement Therapy in Hypoparathyroidism: A Meta-Analysis.

    PubMed

    Liu, X-X; Zhu, X-Y; Mei, G-H

    2016-06-01

    This study investigated the effect of human parathyroid hormone replacement therapy on specific disease-related outcomes in patients with hypoparathyroidism. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until January 13, 2015 for randomized trials using the following search terms: hypoparathyroidism, parathyroid hormone/PTH, and hormone replacement therapy. Five randomized controlled trials (n=245) that investigated effect of either PTH (1-34) (3 trials) or PTH (1-84) (2 trials) on serum calcium, phosphate, 1, 25-dihydroxyvitamin D, 25-dihydroxyvitamin D levels, and urine level of calcium were included in the meta-analysis. Both PTH (1-34) and PTH (1-84) therapies were not associated with change in serum calcium level compared with calcitriol/placebo. The level of 24-h urine calcium excretion had a significant decrease in PTH (1-34)-treated group compared placebo/calcitriol (control) group (p≤0.012). PTH (1-34) did not change serum phosphate (p=0.053). PTH (1-84) did not change level of 24-h urine calcium excretion compared with control (p≥0.214) but it did decrease the levels of serum phosphorous (p=0.000). Both PTH-replacement therapies were not associated with change in serum 1,25-dihydroxyvitamin D level compared with control (p≥0.606), but were associated with a significant decrease in serum 25-dihydroxyvitamin D levels (p≤0.04). In conclusion, although the number of randomized trial is limited, our meta-analysis suggests that PTH (1-34) replacement therapy may maintain the serum calcium levels in the normal range by reducing the levels of urine calcium excretion, and both replacement therapies may maintain 1,25-dihydroxyvitamin D serum levels by reducing serum level of 25-dihydroxyvitamin D. PMID:27254756

  2. The Utility of Intraoperative Bilateral Internal Jugular Venous Sampling With Rapid Parathyroid Hormone Testing

    PubMed Central

    Ito, Fumito; Sippel, Rebecca; Lederman, Julie; Chen, Herbert

    2007-01-01

    Objective: To determine the utility of routine perioperative bilateral internal jugular venous sampling of parathyroid hormone (BIJ PTH) for localization during parathyroid surgery. Summary Background Data: Venous sampling for PTH is a useful tool for parathyroid localization in patients undergoing reoperative surgery for hyperparathyroidism (HPT). With the development of intraoperative rapid PTH (ioPTH) testing, internal jugular PTH sampling with ioPTH testing to guide operative localization has been shown to be possible in select, difficult cases. However, the value of BIJ PTH for patients with HPT is unclear. Methods: Between May 2004 and February 2006, 216 consecutive patients underwent neck exploration for HPT by one surgeon. Of these, 168 patients had BIJ PTH. Internal jugular venous blood was drawn from both left and right sides and analyzed for PTH using a rapid PTH assay. BIJ PTH levels were defined as lateralizing if >5% differences were observed between the right and left internal jugular vein samples. Results: Of the 168 patients, 120 (71.4%) had a single parathyroid adenoma, 15 (8.9%) had double adenoma, and 33 (19.6%) had hyperplasia. The cure rate after parathyroidectomy was 98.2%. There were no complications related to BIJ PTH sampling. Sensitivity and positive predictive value of BIJ PTH for primary hyperparathyroidism were 80% and 71%, respectively. BIJ PTH was diagnostic in 95 cases (62.9%) in primary HPT. BIJ PTH successfully localized an abnormal gland in 26 of 45 (57.8%) in patients with negative sestamibi scanning. BIJ PTH was especially helpful in 18 of 168 (10.7%) cases when intraoperative peripheral parathyroid hormone did not fall by 50% and BIJ PTH successfully localized the hyperfunctioning glands. Conclusions: In patients with HPT, BIJ PTH is safe and effective, providing additional localization information in the majority of cases. BIJ PTH is particularly useful in the setting of negative sestamibi scanning and in complex multigland

  3. 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells.

    PubMed

    Ritter, C S; Armbrecht, H J; Slatopolsky, E; Brown, A J

    2006-08-01

    Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1alpha-hydroxylase (1alphaOHase), but documentation of the 1alphaOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D(3) (25(OH)D(3)) to 1,25-dihydroxyvitamin D(3) (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D(3) and 1,25(OH)(2)D(3) in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1alphaOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D(3) by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D(3) suppressed PTH secretion and mRNA (ED(50)=2 nM), but was several hundred times less potent than 1,25(OH)(2)D(3). The lower potency of 25(OH)D(3) correlated with its lower VDR affinity. bPTCs converted 25(OH)D(3) to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1alphaOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D(3)-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D(3). In conclusion, 25(OH)D(3) suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR. PMID:16807549

  4. Proliferation of endothelial component of parathyroid gland in multiple endocrine neoplasia type 1. Potential relationship with a mitogenic factor.

    PubMed Central

    D'Adda, T.; Amorosi, A.; Bussolati, G.; Brandi, M. L.; Bordi, C.

    1993-01-01

    The basic fibroblast growth factor-like mitogen detected in the plasma of patients with the multiple endocrine neoplasia type 1 (MEN-1) syndrome was found to have a specific mitogenic effect on parathyroid endothelial cells in vitro. To investigate its pathogenic role in humans, the endothelial component of parathyroid glands was evaluated by ultrastructural morphometry in six MEN-1 patients. The results were compared with those found in six patients with uremic hyperparathyroidism (UHPT) and in three subjects with histologically normal glands. Plasma mitogenic activity was found in all MEN-1 patients but not in those with UHPT or in normal subjects. All morphometric parameters investigated (fractional volume and nuclear density of capillary endothelial cells, volume fraction and number per unit area of capillaries) showed 1.5- to 2-fold higher values in patients with MEN-1 than in those with UHPT (P < 0.05). In contrast, no difference was found between MEN-1 cases and normal subjects. Quantitative evaluation of parathyroid pericytes yielded results similar to those of endothelial cells. These data indicate that the proliferation of parathyroid cells in MEN-1 patients is accompanied by parallel increase in the associated endothelial component that does not occur in patients with UHPT and may support the hypothesis of an in vivo role of the MEN-1 mitogen factor on the endothelial component of parathyroid glands in MEN-1 patients. Images Figure 1 PMID:8102033

  5. Combined transcervical and thoracoscopic mediastinal parathyroid adenoma resection.

    PubMed

    Siddiqi, Mohammad Salman; Al Badai, Yahya; Al Kemyani, Nasser A; Al Kindi, Adil H

    2016-07-01

    The routine approach for excision of a parathyroid adenoma is transcervical, but this approach is inadequate when the gland is located in the mediastinum. Traditionally, these cases have required a sternotomy or thoracotomy. We used a combined transcervical and video-assisted thoracoscopic surgery approach to resect a parathyroid adenoma that extended to the middle mediastinum. PMID:27206778

  6. Parathyroid Carcinoma in a 10 Years Old Female Child.

    PubMed

    Rahman, M M; Karim, S S; Joarder, A I; Mubin, S; Abir, M M; Morshed, M S

    2015-07-01

    Parathyroid carcinoma (PC) is a rare cause of hypercalcaemia in children. Only 7 cases of PC have been reported so far in the world journal. The authors report the 8th case of parathyroid carcinoma in children less than 16 years of age. A 10 year old girl presented with difficulty in walking, dorsiflexion and ulnar deviation of both wrist joints and occasional pain in the central abdomen of about two years duration. Biochemical investigations revealed serum calcium 12.2 mg/dL (normal 9-11 mg/dL), serum alkaline phosphate 4992 U/L (normal 50-136 U/L), PTH (parathyroid hormone) 2217 pg/ml (normal 9-80 pg/ml). Parathyroid scintigraphy localized the lesion in the left parathyroid gland. X-ray showed bilateral coxa vera, genu valgus deformity and multiple stress fractures in both wrist joints. Histopathology confirmed PC with capsular and vascular invasion. PMID:26329966

  7. Parathyroid carcinoma, a rare cause of primary hyperparathyroidism

    PubMed Central

    Alperstein, Adam; Bhayani, Rajendra

    2014-01-01

    A 45 year-old woman who presented with non-specific neck and shoulder pain, was found to have mild hypercalcaemia, markedly elevated parathyroid hormone levels, and an irregular parathyroid gland on imaging. The patient underwent a parathyroidectomy and the pathology report came back positive for parathyroid carcinoma with muscular invasion. Parathyroid carcinoma is an exceptionally rare cause of primary hyperparathyroidism and can have a poor prognosis due to metastases and a high propensity to recur after resection. Reports of non-functioning parathyroid carcinomas tend to behave even more aggressively. Repeat imaging on this patient showed residual cancer present, so the patient underwent a second surgery with radical neck dissection and has since been doing very well postoperatively. Diagnosis and treatment is challenging and it is critical to continuously follow-up for recurrent disease. PMID:25139918

  8. Identifying Parathyroid Glands With Carbon Nanoparticle Suspension Does Not Help Protect Parathyroid Function in Thyroid Surgery: A Prospective, Randomized Control Clinical Study.

    PubMed

    Liu, Xu; Chang, Shi; Jiang, Xiaolin; Huang, Peng; Yuan, Zhengtai

    2016-08-01

    Objective We aim to evaluate the technique of identifying parathyroid glands with carbon nanoparticle suspension (CNPS) in thyroid surgeries from the perspectives of degrees of declining intact parathyroid hormone (iPTH), operation time, and time of postoperative stay. Methods A total of 156 patients who underwent thyroid surgeries in General Surgical Department of Xiangya Hospital between May 2012 and May 2015 were involved in the study. A total of 78 patients were injected with CNPS during the surgery (CNPS group); the other 78 patients received normal saline (control group). Cases were classified into 3 surgical approaches: conventional partial thyroidectomy, conventional total thyroidectomy, and endoscopic partial thyroidectomy. Degrees of declining iPTH were tested to determine the severity of parathyroid injury. Operation time and postoperative hospital stay time were recorded. A P value of less than .05 was considered statistically significant. Results For levels of declining iPTH, there was no statistically significant (ss) difference in conventional thyroid surgery. In endoscopic partial thyroidectomy, it was 23.37 ± 16.20 versus 11.94 ± 11.23 pg/mL (P = .02, ss). The operation time of conventional total thyroidectomy was 210.10 ± 83.75 versus 164.84 ± 69.22 minutes (P = .03, ss), while it was 193.04 ± 75.53 versus 127.67 ± 60.06 minutes (P = .007, ss) in endoscopic thyroidectomy. Conclusions CNPS is not beneficial for protecting the function of parathyroid gland in thyroid surgery from the perspective of declining iPTH. Applying CNPS in conventional total thyroidectomy and endoscopic partial thyroidectomy will also lead to significantly prolonged operation time. PMID:26783268

  9. Determinants of quaternary association in legume lectins

    PubMed Central

    Brinda, K.V.; Mitra, Nivedita; Surolia, Avadhesha; Vishveshwara, Saraswathi

    2004-01-01

    It is well known that the sequence of amino acids in proteins code for its tertiary structure. It is also known that there exists a relationship between sequence and the quaternary structure of proteins. The question addressed here is whether the nature of quaternary association can be predicted from the sequence, similar to the three-dimensional structure prediction from the sequence. The class of proteins called legume lectins is an interesting model system to investigate this problem, because they have very high sequence and tertiary structure homology, with diverse forms of quaternary association. Hence, we have used legume lectins as a probe in this paper to (1) gain novel insights about the relationship between sequence and quaternary structure; (2) identify the sequence motifs that are characteristic of a given type of quaternary association; and (3) predict the quaternary association from the sequence motif. PMID:15215518

  10. Studies on the volume and the activity of the parathyroid glands in osteoporosis of disuse in the adult rat.

    PubMed

    Sevastikoglou, J A; Mattsson, S

    1976-01-01

    Inactivity of the right hind leg was brought about in adult male Sprague-Dawley rats by a) immobilisation in a plaster cast and b) by resection of the sciatic nerve. Determinations of the volume and the activity of the parathyroid glands by morphological methods showed that the parathyroids were, on the whole, not affected by the treatment. Some significant differences observed in some examined parameters should, however, suggest hypofunction of the glands. The serum-calcium level was significantly higher in the treated than in the control rats in the first experiment. No significant differences in serum calcium between treated and control animals were observed in the second experiment. These observations were considered to indicate that the development of localised osteoporosis in these two forms of inactivity did not depend on hyperactivity of the parathyroids. The observed differences in serum-calcium content between the two experiments may suggest that localised osteoporosis in the two cases developed through different pathomechanisms. PMID:1070896

  11. Oxyphil Cell Parathyroid Adenomas Causing Primary Hyperparathyroidism: a Clinico-Pathological Correlation.

    PubMed

    Howson, Pamela; Kruijff, Schelto; Aniss, Ahmad; Pennington, Thomas; Gill, Anthony J; Dodds, Tristan; Delbridge, Leigh W; Sidhu, Stan B; Sywak, Mark S

    2015-09-01

    Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically silent. It has been our clinical impression that these adenomas present more often than previously thought and may manifest a more severe form of primary hyperparathyroidism than classical adenoma. The aim of this study was to describe the incidence and clinical presentation of OPA. An observational case-control study was undertaken. The study group comprised patients undergoing parathyroidectomy for PHPT where the final pathology confirmed OPA. The controls were made up of an age- and sex-matched group of patients having parathyroidectomy in the same time period where the final pathology confirmed a classical or non-oxyphil adenoma. OPA were defined as parathyroid tumours containing >75% oxyphilic cells. The OPA cases were obtained by reviewing all histopathology slides over an 11-year period (2002-12) where the reports contained the words 'oxyphil' or 'oxyphilic' parathyroid adenomas. These were then reviewed by two independent pathologists to confirm a diagnosis of OPA. The primary outcome measures were preoperative serum calcium and parathyroid hormone (PTH) levels. Secondary outcome measures were symptoms at presentation, accuracy of preoperative localization studies, parathyroid gland weight following surgery, and type of surgery undertaken. In the period 2002-2012, 2739 patients underwent surgery for PHPT. Following pathological review, 91 cases were confirmed as being OPA and formed the study group. A control group (n = 91) from the same period was selected following matching on the basis of age at presentation and sex. OPA were associated with higher preoperative serum calcium (10.84 versus 10.48 mg/dL, p < 0.001) and parathyroid hormone (139 versus 64 ng/L, p < 0.001). At presentation, a lower proportion of OPA cases had asymptomatic disease (15 versus 29%, p = 0.03). There was

  12. Huge Parathyroid Adenoma with Dysphagia Presentation; A Case Report from Southern Iran.

    PubMed

    Ziaeean, Bizhan; Sohrabi-Nazari, Sahar

    2016-09-01

    Parathyroid adenoma is a benign tumor of the parathyroid glands. The cause of most parathyroid adenomas is unknown. Parathyroid adenoma increases the secretion of parathyroid hormone and results in primary hyperparathyroidism. High amounts of parathyroid hormone in the blood cause the imbalance of calcium, which leads to various complications such as kidney stones, depression, lethargy, nausea, vomiting, abdominal pain, myalgia, bone and joint pain, hoarseness, etc. Oropharyngeal dysphagia is defined as having problem in swallowing due to abnormalities in the structure and function of oropharynx and other related organs. The exact prevalence of dysphagia caused by parathyroid adenoma is unknown, but since this complication can lead to increased mortality and morbidity, its diagnosis is important. It is difficult to distinguish parathyroid malignancies from parathyroid adenoma even after surgery. Therefore, the final diagnosis is possible through surgery and histopathological evaluation. Here, a case of parathyroid adenoma with first presentation of generalized weakness and dysphagia has been reported. PMID:27582595

  13. Huge Parathyroid Adenoma with Dysphagia Presentation; A Case Report from Southern Iran

    PubMed Central

    Ziaeean, Bizhan; Sohrabi-Nazari, Sahar

    2016-01-01

    Parathyroid adenoma is a benign tumor of the parathyroid glands. The cause of most parathyroid adenomas is unknown. Parathyroid adenoma increases the secretion of parathyroid hormone and results in primary hyperparathyroidism. High amounts of parathyroid hormone in the blood cause the imbalance of calcium, which leads to various complications such as kidney stones, depression, lethargy, nausea, vomiting, abdominal pain, myalgia, bone and joint pain, hoarseness, etc. Oropharyngeal dysphagia is defined as having problem in swallowing due to abnormalities in the structure and function of oropharynx and other related organs. The exact prevalence of dysphagia caused by parathyroid adenoma is unknown, but since this complication can lead to increased mortality and morbidity, its diagnosis is important. It is difficult to distinguish parathyroid malignancies from parathyroid adenoma even after surgery. Therefore, the final diagnosis is possible through surgery and histopathological evaluation. Here, a case of parathyroid adenoma with first presentation of generalized weakness and dysphagia has been reported. PMID:27582595

  14. Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells.

    PubMed

    Kayamori, Kou; Sakamoto, Kei; Nakashima, Tomoki; Takayanagi, Hiroshi; Morita, Kei-Ichi; Omura, Ken; Nguyen, Su Tien; Miki, Yoshio; Iimura, Tadahiro; Himeno, Akiko; Akashi, Takumi; Yamada-Okabe, Hisafumi; Ogata, Etsuro; Yamaguchi, Akira

    2010-02-01

    We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast formation. Microarray analyses performed on 43 human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM) derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u-1) stimulated Rankl expression in stromal cells and osteoclast formation. Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody. CM derived from all of the OSCC cell lines effectively induced IL-6 expression in stromal cells, and the induction was partially blocked by anti-PTHrP antibody. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6. PMID:20035059

  15. Near-infrared autofluorescence for the detection of parathyroid glands

    NASA Astrophysics Data System (ADS)

    Paras, Constantine; Keller, Matthew; White, Lisa; Phay, John; Mahadevan-Jansen, Anita

    2011-06-01

    A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.

  16. Resection of a large ectopic parathyroid adenoma: A case report

    PubMed Central

    Sato, Seijiro; Kitahara, Akihiko; Koike, Terumoto; Hashimoto, Takehisa; Ohashi, Riuko; Motoi, Noriko; Tsuchida, Masanori

    2016-01-01

    Introduction Parathyroid adenomas are the most common cause of primary hyperparathyroidism. However, cases of parathyroid adenomas greater than 4 cm with osteitis fibrosa cystica are extremely rare. Herein, we report a case of resection of a large ectopic mediastinal parathyroid adenoma. Case presentations A 46-year-old female with chief complaints of bone pain and gait disturbance was referred to our hospital. Physical examination revealed many mobile teeth in her oral cavity, distortion of the vertebral body, and bowlegs. Laboratory tests showed hypercalcemia, hypophosphatemia, and elevated serum levels of intact parathyroid hormone. Chest CT revealed a 42-mm well–defined, enhancing mass in front of the left-sided tracheal bifurcation. Her findings were diagnosed as primary hyperparathyroidism due to an ectopic mediastinal parathyroid tumor. We performed a median sternotomy and resected the tumor. The tumor was a solid, yellowish-brown mass measuring 42 × 42 mm. Pathologically, the tumor consisted mainly of chief cells with some oxyphil cells; there were no necrotic areas or nuclear atypia, and few mitotic figures. We diagnosed the tumor as an ectopic mediastinal parathyroid adenoma. Eight months after the resection, her serum calcium, phosphorus, and intact PTH levels were normal. Discussion and conclusions Parathyroid adenomas and parathyroid carcinomas have disparate natural histories, but they can be difficult to differentiate on the basis of preoperative clinical characteristics. We believe that long-term follow-up of these cases is required because there have been few reports on the postoperative natural history of large parathyroid adenomas. PMID:27078868

  17. Parathyroid gland ultrasound patterns and biochemical findings after one-year cinacalcet treatment for advanced secondary hyperparathyroidism.

    PubMed

    Vulpio, Carlo; Bossola, Maurizio; De Gaetano, Annamaria; Maresca, Giulia; Di Stasio, Enrico; Zagaria, Luca; Luciani, Giovanna; Giordano, Alessandro; Castagneto, Marco

    2010-04-01

    Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium-phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 +/- 5.9 and 13.0 +/- 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 +/- 416.3 and 556.8 +/- 480.8 mm(3), respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns. PMID:20438540

  18. Effects of Parathyroid Hormone Administration on Bone Strength in Hypoparathyroidism.

    PubMed

    Rubin, Mishaela R; Zwahlen, Alexander; Dempster, David W; Zhou, Hua; Cusano, Natalie E; Zhang, Chengchen; Müller, Ralph; Bilezikian, John P

    2016-05-01

    The microstructural skeletal phenotype of hypoparathyroidism (HypoPT), a disorder of inadequate parathyroid hormone secretion, is altered trabecular microarchitecture with increased trabecular bone volume and thickness. Using 2-D histomorphometric analysis, we previously found that 2 years of PTH(1-84) in HypoPT is associated with reduced trabecular thickness (Tb.Th) and an increase in trabecular number (Tb.N). We have now utilized direct 3-D microstructural analysis to determine the extent to which these changes may be related to bone strength. Iliac crest bone biopsies from HypoPT subjects (n = 58) were analyzed by microcomputed tomography (μCT) and by microfinite element (μFE) analysis. Biopsies were performed at baseline and at 1 or 2 years of recombinant human PTH(1-84) [rhPTH(1-84)]. In a subset of subjects (n = 13) at 3 months, we demonstrated a reduction in trabecular separation (Tb.Sp, 0.64 ± 0.1 to 0.56 ± 0.1 mm; p = 0.005) and in the variance of trabecular separation (Tb.SD, 0.19 ± 0.1 to 0.17 ± 0.1 mm; p = 0.01), along with an increase in bone volume/total volume (BV/TV, 26.76 ± 10.1 to 32.83 ± 13.5%; p = 0.02), bone surface/total volume (BS/TV, 3.85 ± 0.7 to 4.49 ± 1.0 mm(2) /mm(3) ; p = 0.005), Tb.N (1.84 ± 0.5 versus 2.36 ± 1.3 mm(-1) ; p = 0.02) and Young's modulus (649.38 ± 460.7 to 1044.81 ± 1090.5 N/mm(2) ; p = 0.049). After 1 year of rhPTH(1-84), Force increased (144.08 ± 102.4 to 241.13 ± 189.1 N; p = 0.04) and Young's modulus tended to increase (662.15 ± 478.2 to 1050.80 ± 824.1 N/m(2) ; p = 0.06). The 1-year change in cancellous mineralizing surface (MS/BS) predicted 1-year changes in μCT variables. The biopsies obtained after 2 years of rhPTH(1-84) showed no change from baseline. These data suggest that administration of rhPTH(1-84) in HypoPT is associated with transient changes in key parameters associated with

  19. Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation

    PubMed Central

    Kimura, Shigemi; Yoshioka, Kowasi

    2014-01-01

    The ZHTc6-MyoD embryonic stem cell line expresses the myogenic transcriptional factor MyoD under the control of a tetracycline-inducible promoter. Following induction, most of the ZHTc6-MyoD cells differentiate to myotubes. However, a small fraction does not differentiate, instead forming colonies that retain the potential for myocyte differentiation. In our current study, we found that parathyroid hormone type 1 receptor (PTH1R) expression in colony-forming cells at 13 days after differentiation was higher than that in the undifferentiated ZHTc6-MyoD cells. We also found that PTH1R expression was required for myocyte differentiation, and that parathyroid hormone accelerated the differentiation. Our analysis of human and mouse skeletal muscle tissues showed that most cells expressing PTH1R also expressed Pax7 and CD34, which are biomarkers of satellite cells. Furthermore, we found that parathyroid hormone treatment significantly improved muscle weakness in dystrophin-deficient mdx mice. This is the first report indicating that PTH1R and PTH accelerate myocyte differentiation. PMID:24919035

  20. Parathyroid hormone pulsatility: physiological and clinical aspects

    PubMed Central

    Chiavistelli, Silvia; Giustina, Andrea; Mazziotti, Gherardo

    2015-01-01

    Parathyroid hormone (PTH) secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30% is secreted in low-amplitude and high-frequency bursts occurring every 10–20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis. PMID:26273533

  1. The history of the parathyroid surgery.

    PubMed

    Toneto, Marcelo Garcia; Prill, Shandi; Debon, Leticia Manoel; Furlan, Fernando Zucuni; Steffen, Nedio

    2016-01-01

    The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment. RESUMO Os autores fizeram uma revisão dos principais aspectos históricos da progressão do conhecimento sobre o tratamento cirúrgico do hiperparatireoidismo. Por meio de revisão bibliográfica, foram analisados artigos selecionados sobre a história da evolução do conhecimento anatômico, fisiológico, patológico e cirúrgico das glândulas paratireoides. Devido às suas características anatômicas peculiares, as paratireoides foram as últimas das glândulas endócrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado até as primeiras décadas do Século XX. A evolução tecnológica ocorrida nos últimos 30 anos facilitou sobremaneira a localização das glândulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgião experiente e dedicado ao tratamento dessa enfermidade ainda é fundamental para a excelência do tratamento. PMID:27556546

  2. Immunoprecipitation of the parathyroid hormone receptor

    SciTech Connect

    Wright, B.S.; Tyler, G.A.; O'Brien, R.; Caporale, L.H.; Rosenblatt, M.

    1987-01-01

    An /sup 125/I-labeled synthetic analog of bovine parathyroid hormone, (8-norleucine,18-norleucine,34-tyrosine)PTH-(1-34) amide ((Nle)PTH-(1-34)-NH/sub 2/), purified by high-pressure liquid chromatography (HPLC), was employed to label the parathyroid hormone (PTH) receptor in cell lines derived from PTH target tissues: the ROS 17/2.8 rat osteosarcoma of bone and the CV1 and COS monkey kidney lines. After incubation of the radioligand with intact cultured cells, the hormone was covalently attached to receptors by using either a photoaffinity technique or chemical (affinity) crosslinking. In each case, covalent labeling was specific, as evidenced by a reduction of labeling when excess competing nonradioactive ligand was present. After covalent attachment of radioligand, membranes were prepared form the cells and solubilized in the nonionic detergent Nonidet P-40 or octyl glucoside. Analysis of the immunoprecipitate on NaDod-SO/sub 4//polyacrylamide gel electrophoresis followed by autoradiography revealed the presence of a doublet of apparent molecular mass 69-70 kDa. Specifically labeled bands of approximate molecular mass 95 and 28 kDa were also observed. The anti-PTH IgG was affinity purified by passage over a PTH-Sepharose column and used to made an immunoaffinity column. These studies suggest that the use of an anti-PTH antiserum that binds receptor-bound hormone is likely to be a useful step in the further physicochemical characterization and purification of the PTH receptor.

  3. Parathyroid adenoma on the ipsilateral side of thyroid hemiagenesis.

    PubMed

    Kroeker, Teresa R; Stancoven, Kevin M; Preskitt, John T

    2011-04-01

    We present a case of a parathyroid adenoma on the ipsilateral side of thyroid hemiagenesis-which, to our knowledge, is the third reported case of this entity. A 41-year-old man with nephrolithiasis was found to have elevated calcium and intact parathyroid hormone levels. Both ultrasound and technetium sestamibi scintigraphy with single photon emission computed tomography confirmed left thyroid hemiagenesis and an adenoma in the left inferior thyroid bed. The patient underwent left neck exploration, which confirmed left thyroid hemiagenesis and a left inferior parathyroid adenoma. The left inferior parathyroid gland was resected. The patient was discharged home the same day of surgery and has remained normocalcemic for 14 months without evidence of hyperparathyroidism. PMID:21566751

  4. Parathyroid adenoma presenting as a brown tumour of the mandible.

    PubMed

    Amin, Kavit; Fu, Bertram; Barbaccia, Carmelo

    2012-01-01

    Background. Parathyroid adenoma is the commonest cause of primary hypercalcaemia and usually presents with symptoms/signs of hypercalcaemia. This paper highlights an unusual presentation. Case Report. A 27-year-old female presented with a painful left mandibular swelling, suspicious of neoplasia. A computed tomography (CT) guided biopsy was performed. Based on the histology result, serum calcium was carried out, confirming hypercalcaemia. A left inferior parathyroid adenoma was subsequently removed. CT mandible showed extensive erosive lesions at the left 2nd/3rd inferior molar roots with protrusion to adjacent soft tissues. USS revealed a hypoechoic lesion on the left inferior parathyroid gland. Sestamibi scan showed a focus of MIBI uptake and retention at the inferior aspect of the left thyroid lobe. Conclusion. This case highlights the importance of a thorough history and examination. Clinicians should always bear in mind atypical presentations of parathyroid adenomas, with the need to exclude this differential in the presence of hypercalcaemia. PMID:23251179

  5. [Ectopic parathyroid glands. Imaging methods and surgical access].

    PubMed

    Fialová, M; Adámková, J; Adámek, S; Libánský, P; Kubinyi, J

    2014-08-01

    We discuss the benefits of imaging methods in localizing ectopic parathyroid glands in patients with primary hyperparathyroidism. The ectopic localizations are discussed within the context of the orthotopic norm. In the sample of 123 patients, a 23% rate of ectopic parathyroid glands was detected. Three selected case studies are presented, supporting the benefit of SPECT/CT imaging in terms of surgical access strategy selection. PMID:25230388

  6. Endoscopic surgery of the parathyroid glands: methods and principles.

    PubMed

    Prades, J-M; Gavid, M; Timoshenko, A T; Richard, C; Martin, C

    2013-06-01

    Targeted endoscopic parathyroidectomy without gas insufflation is a relatively non-invasive means of discovering and resecting parathyroid adenomas in sporadic primary hyperparathyroidism. This standardized technique depends on the quality of the preoperative imaging: cervical ultrasound and sestamibi scintigraphy, and can be optimized by preoperative insertion of an ultrasound-guided "harpoon" and rapid peroperative parathyroid hormone analysis. Failure rates range between 1.7% and 4%. PMID:23562229

  7. Ultrasensitive Impedimetric Biosensor Fabricated by a New Immobilisation Technique for Parathyroid Hormone.

    PubMed

    Özcan, Hakkı Mevlüt; Yildiz, Kübra; Çakar, Cansu; Aydin, Tuba; Asav, Engin; Sağiroğlu, Ayten; Sezgintürk, Mustafa Kemal

    2015-07-01

    This paper presents a novel ultrasensitive and rapid impedimetric biosensor with new immobilisation materials for parathyroid hormone (PTH) with the aim to determine the PTH level in serum for the diagnosis and monitoring of parathyroid diseases such as hyperparathyroidism, adenoma, and thyroid cancer. The interaction between PTH and the biosensor was investigated with an electrochemical method. The biosensor was based on the gold electrode modified by mercaptohexanol (6-MHL). Anti-parathyroid hormone (anti-PTH) was covalently immobilised onto a self-assembled monolayer (SAM) by using epiclorhidrina (EPI) with ethanolamine (EA). The EPI-EA interaction represents the first use of these for the construction of biosensors in published reports. The immobilisation of the anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscopy (SEM) techniques. After the optimisation studies of immobilisation materials such as 6-MHL, EPI, EA and glutaraldehyde, linearity, repeatability and sensitivity of biosensor were evaluated as the performance of biosensor. PTH was detected within a linear range of 0.1-0.6 pg/ml, and the detection limit was 0.1 fg/ml. The specificity of the biosensor was also investigated. Finally, the described biosensor was used to detect the PTH levels in artificial serum samples. PMID:25935225

  8. Non-functioning parathyroid gland carcinoma: case report.

    PubMed

    Krvavica, Ana; Kovacić, Marijan; Baraka, Ivan; Rudić, Milan

    2011-06-01

    Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy. PMID:22263388

  9. Parathyroid cyst presenting as acute pancreatitis: report of a case.

    PubMed

    Kim, Mi-Young; Chung, Cho-Yun; Kim, Jong-Sun; Myung, Dae-Seong; Cho, Sung-Bum; Park, Chang-Hwan; Kim, Young; Joo, Young-Eun

    2013-12-01

    We report the first case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid cyst in a 67-year-old man. Laboratory investigation revealed increased serum amylase and lipase, increased serum ionized calcium and parathyroid hormone (PTH) levels, and decreased serum phosphate, indicating pancreatitis and primary hyperparathyroidism (PHPT). Abdominal computed tomography (CT) revealed mild swelling of the pancreatic head with peri-pancreatic fat infiltration and fluid collection around the pancreatic tail. Ultrasonography and CT of the neck showed a cystic lesion at the inferior portion of the left thyroid gland, suggesting a parathyroid cyst. There was no evidence of parathyroid adenoma by 99mTc sestamibi scintigraphy. PHPT caused by a functioning parathyroid cyst was suspected. The patient underwent surgical resection of the functioning parathyroid cyst owing to his prolonged hypercalcemia. At 3 weeks after the operation, his serum levels of PTH, total calcium, ionized calcium, inorganic phosphate, amylase, and lipase were normalized. At the follow-up examinations, he has remained asymptomatic. PMID:24400215

  10. A Rare Case of Concomitant Maxilla and Mandible Brown Tumours, Papillary Thyroid Carcinoma, Parathyroid Adenoma, and Osteitis Fibrosa Cystica

    PubMed Central

    Nunes, Thaís Borguezan; Bologna, Sheyla Batista; Witzel, Andréa Lusvarghi; Nico, Marcello Menta Simonsen; Lourenço, Silvia Vanessa

    2016-01-01

    Objective. The brown tumour of hyperparathyroidism is a result of a metabolic disorder caused by primary hyperparathyroidism. Report. We described a case of a 37-year-old female patient presenting bimaxillary intraoral lesions and swelling in the neck. Incisional biopsy of the oral lesion was performed and histopathological examination revealed a central giant cell lesion composed by intense haemorrhagic exudate, abundant presence of giant cells, and areas with hemosiderin pigment. The patient also presented high levels of serum calcium and parathyroid hormone, hyperfunctioning parathyroid tissue, bilateral parenchymal nephropathy, and densitometry lower than expected, showing an advanced stage of osteitis fibrosa cystica. Synchronous parathyroid adenoma and papillary thyroid carcinoma were confirmed by imaging exams and histopathologically. Conclusion. The composition of all the clinical, pathological, and imaging findings led to the final diagnosis of brown tumour of hyperparathyroidism. The occurrence of parathyroid adenoma, papillary thyroid carcinoma, and brown tumours of hyperparathyroidism in their late stage (osteitis fibrosa cystica) associated with oral brown tumours involving the mandible and maxilla is extremely rare. PMID:26881146

  11. Triazolopyrimidine (trapidil), a platelet-derived growth factor antagonist, inhibits parathyroid bone disease in an animal model for chronic hyperparathyroidism

    NASA Technical Reports Server (NTRS)

    Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

    2003-01-01

    Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

  12. Kinetics of parathyroid hormone after parathyroidectomy in chronic hemodialysis patients.

    PubMed

    Skalli, Z; Elouazzani, H; Alhamany, Z; Mattous, M; Benamar, L; Bayahia, R; Belkouchi, M; El Malki, HadjOmar; Ouzeddoun, N

    2015-11-01

    Secondary hyperparathyroidism is a common complication in chronic renal failure. The treatment in some cases requires parathyroidectomy. The kinetics of the parathyroid hormone (PTH) levels after surgery helps to evaluate the efficacy of parathyroidectomy. Prospective analysis was made of the kinetics of intact PTH (iPTH) after parathyroidectomy in 10 chronic hemodialysis (HD) patients who had secondary hyperparathyroidism. We determined the levels of iPTH before surgery and its evolution after parathyroidectomy at regular intervals: Day 0, D7, D15, D30 and D90. The mean age of our patients was 40 ± 13 years, with a sex ratio of 1. The mean duration on HD was 122 ± 63 months. The duration of secondary hyperparathyroidism varied from one year to 12 years. All patients had received medical treatment for hyperparathyroidism. The indications for parathyroidectomy included resistance to medical treatment in seven cases, development of brown tumors in two cases and soft tissue calcifications in one case. All patients had radiographic evidence of hyperparathyroidism. The parathyroidectomy was sub-total in all patients, 6/8 in four cases and 7/8 in six cases. The mean iPTH level was 2341 ± 1946 pg/mL before surgery. A sharp drop in this level was noticed on D0, with a median of 92 pg/mL and, thereafter, the levels were 79 pg/mL on D7, 25 pg/mL on D15 and 36 pg/mL after 1 month. At 3 months post-surgery, the mean iPTH level was 302 pg/mL. Histological examination of the resected gland showed parathyroid hyperplasia in all patients. In our series, the efficacy of sub-total parathyroidectomy was satisfactory with rapid normalization of PTH, which is consistent with the literature data. Sub-total parathyroidectomy still has a place in the treatment of secondary hyperparathyroidism in chronic renal failure. Its indications should be limited to cases resistant to medical treatment and, in particular, in cases with occurrence of complications. PMID:26586059

  13. Potential role for carbon nanoparticles identification and preservation in situ of parathyroid glands during total thyroidectomy and central compartment node dissection

    PubMed Central

    Gu, Jialei; Wang, Jiafeng; Nie, Xilin; Wang, Wendong; Shang, Jinbiao

    2015-01-01

    Objective: To determine the potential role of intraoperative carbon nanoparticles (CN) injections for identification and preservation of parathyroid glands, thereby reducing the postoperative hypocalcaemia. Methods: 100 patients with thyroid cancer who underwent total thyroidectomy and central compartment node dissection (CCND) were randomly assigned to receive intraoperative injection of (CN) or not for identifying and preserving normal parathyroid glands. Results: There was no significantly difference for preoperative and postoperative parathyroid hormone (PTH) levels between the CN and control group (P>0.05). The levels of albumin-adjusted serum calcium (AASC) before surgery and at day 1 and 1 month after surgery did not reach the significant difference between the two groups (P>0.05). However, the patients in CN group had the higher level of AASC at day 3 after surgery than those in control group (P=0.044). Transient postoperative hypoparathyroidism occurred in 24 (48%) patients in CN group and 28 (56%) in control groups, respectively (P=0.423). The incidence of transient postoperative hypocalcemia was 20% (10/50) in CN group and 24% (12/50) in control groups, respectively (P=0.629). Conclusions: Carbon nanoparticles can make the thyroid gland and the central lymph node black-stained, but no-stained for parathyroid glands. After rapidly identifying parathyroid and distinguishing it from thyroid and lymph nodes by carbon nanoparticles, complete lymph node dissection and preservation of parathyroid glands become feasible during total thyroidectomy with neck lymph node dissection. After identification, strict adherence to capsular dissection remains essential for safe preservation in situ of the parathyroid glands and their blood supply. PMID:26309638

  14. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    PubMed

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions. PMID:7870347

  15. Adult Perithyroid and Cervical Thymus-Parathyroid Unit

    PubMed Central

    Handra-Luca, Adriana

    2014-01-01

    Abstract The thymus-parathyroid unit (TPU) occurring in adults is rare. The main symptoms and important clinical findings are as follows: 2 patients presented with neomercazole-resistant Basedow–Graves disease. A third patient presented with thyroid nodules and a fourth patient with a neck mass after thyroid resection for medullary thyroid carcinoma. The main diagnoses were those of thyroid nodules (either in the context of goiter, or not). In the fourth case the diagnosis was of thyroid medullary carcinoma recurrence in the neck. Thyroidectomy was performed in the 2 cases of Basedow–Graves disease and in the third case (wherein selective neck dissection was also performed). In the fourth case, a neck dissection was performed for a possible medullary carcinoma recurrence. A TPU was microscopically detected in 2 cases with perithyroid location, on thyroidectomies for Basedow–Graves disease and in the 2 other cases with neck soft tissue location (associated with thyroid papillary carcinoma and thyroid medullary carcinoma extension). Postsurgical hypocalcemia requiring treatment occurred in both patients with Basedow–Graves disease and in the fourth patient. The presence of TPU should be acknowledged because such lesions can be misdiagnosed as suspect lymph nodes during thyroid surgery for malignant tumors. PMID:25501075

  16. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis

    PubMed Central

    Ferrandon, Sébastien; Feinstein, Timothy N; Castro, Marian; Wang, Bin; Bouley, Richard; Potts, John T; Gardella, Thomas J; Vilardaga, Jean-Pierre

    2011-01-01

    Cell signaling mediated by the G protein-coupled parathyroid hormone receptor type 1 (PTHR) is fundamental to bone and kidney physiology. It has been unclear how the two ligand systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—can effectively operate with only one receptor and trigger different durations of the cAMP responses. Here we analyze the ligand response by measuring the kinetics of activation and deactivation for each individual reaction step along the PTHR signaling cascade. We found that during the time frame of G protein coupling and cAMP production, PTHrP1–36 action was restricted to the cell surface, whereas PTH1–34 had moved to internalized compartments where it remained associated with the PTHR and Gαs, potentially as a persistent and active ternary complex. Such marked differences suggest a mechanism by which PTH and PTHrP induce differential responses, and these results indicate that the central tenet that cAMP production originates exclusively at the cell membrane must be revised. PMID:19701185

  17. Reoperation for parathyroid adenoma: A contemporary experience

    PubMed Central

    Powell, Anathea C.; Alexander, H. Richard; Chang, Richard; Marx, Stephen J.; Skarulis, Monica; Pingpank, James F.; Bartlett, David L.; Hughes, Marybeth; Weinstein, Lee S.; Simonds, William F.; Collins, Michael F.; Shawker, Thomas; Chen, Clara C.; Reynolds, James; Cochran, Craig; Steinberg, Seth M.; Libutti, Steven K.

    2012-01-01

    Background We reviewed reoperations for persistent or recurrent sporadic parathyroid adenoma to evaluate and compare our current results and outcomes to our previous experience. Methods From 1996 to 2008, 237 patients with persistent or recurrent hyperparathyroidism after failed operation underwent reoperation. Patients were re-explored with the assistance of non-invasive and sometimes invasive imaging. Results A missed adenoma was suspected pre-operatively in 163 patients. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%; the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful non-invasive imaging studies (96% positive predictive value (PPV) and 84% PPV respectively). Forty-four percent of patients had a reoperation based solely on non-invasive imaging. Of the invasive procedures performed, arteriography resulted in the best localization (92% PPV). Permanent recurrent laryngeal nerve injury occurred in 1.8%. Conclusion Compared to our prior experience (1982–1995), outcomes remained similar (92% resolution of hypercalcemia and 1.8% recurrent nerve injury currently versus 96% and 1.3% previously). Fewer patients received invasive studies for pre-operative localization (56% vs 73%, respectively). The decreased use of invasive imaging is due to technical improvements and greater confidence in the combination of ultrasonography and sestamibi scanning. PMID:19958942

  18. Parathyroid Hormone Applications in the Craniofacial Skeleton

    PubMed Central

    Chan, H.L.; McCauley, L.K.

    2013-01-01

    Parathyroid hormone (PTH) is known for its ability to ‘build’ bone, with research in this area centered on its use as an osteoporosis therapeutic. Recent interest has developed regarding its potential for regenerative applications such as fracture healing and osseous defects of the oral cavity. Many years of investigation using murine gene-targeted models substantiate a role for signaling at the PTH/PTH-related protein (PTHrP) receptor (PPR) in intramembranous bone formation in the craniofacial region as well as in tooth development. Pre-clinical studies clearly support a positive role of intermittent PTH administration in craniofacial bones and in fracture healing and implant integration. A few human clinical studies have shown favorable responses with teriparatide (the biologically active fragment of PTH) administration. Favorable outcomes have emerged with teriparatide administration in patients with osteonecrosis of the jaw (ONJ). New delivery strategies are in development to optimize targeted application of PTH and to help maximize local approaches. The promising host-modulating potential of PTH requires more information to further its effectiveness for craniofacial regeneration and osseous wound-healing, including a better delineation of cellular targets, temporal effects of PTH action, and improved approaches for local/targeted delivery of PTH. PMID:23071071

  19. Functional parathyroid cystic adenoma: A rare cause of hypercalcemic crisis with primary hyperparathyroidism.

    PubMed

    Sumana, B S; Sabaretnam, M; Sarathi, Vijaya; Savith, Akshatha

    2015-01-01

    We discuss a case of primary hyperparathyroidism caused by a giant cystic parathyroid adenoma presenting with neck swelling and hypercalcemic crisis. Fine-needle aspiration cytology of presumed thyroid swelling from one of the two sites aspirated yielded clear fluid but was not attributed to parathyroid pathology. Elevated serum calcium and intact parathormone (iPTH) levels suggested preoperative parathyroid pathology. Ultrasound neck and sestamibi scan for parathyroid localization were not conclusive. Due to resistant hypercalcemia, the patient underwent emergency bilateral neck exploration and excision of the identified left superior parathyroid cyst along with total thyroidectomy. Monitoring of intra-operative iPTH helped complete removal of hyperfunctioning parathyroid tissue. Histopathological examination confirmed the parathyroid cyst. Cystic parathyroid adenoma should be considered in the differential diagnosis of cystic neck lesions. PMID:26549073

  20. Parathyroid and Calcium Status in Patients with Thalassemia

    PubMed Central

    Goyal, Meenu; Abrol, Pankaj

    2010-01-01

    Thirty patients with thalassemia major receiving repeated blood transfusion were studied to see their serum parathyroid hormone (PTH) and calcium status. Serum PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were determined. Half of these patients, in addition to transfusion, were also supplemented with vitamin D (60,000 IU for 10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h urinary calcium concentrations of the patients receiving transfusions were found to be significantly reduced while their serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were not significantly altered when compared to the respective mean values for the control group. Vitamin D and calcium supplementation significantly increased their serum PTH and calcium levels. Supplementations also increased urinary excretion of calcium. The results thus suggest that patients with thalassemia have hypoparathyroidism and reduced serum calcium concentrations that in turn were improved with vitamin D and calcium supplementation. PMID:21966110

  1. Parathyroid hormone-related peptide expression in tibial dyschondroplasia.

    PubMed

    Farquharson, C; Seawright, E; Jefferies, D

    2001-08-01

    Parathyroid hormone-related peptide (PTHrP) has a key role in the growth of long bones, as it is a negative regulator of growth plate chondrocyte terminal differentiation. We have examined the distribution and gene expression levels of PTHrP in the growth plates of broiler chickens with tibial dyschondroplasia (TD) in order to determine whether increased expression of PTHrP is responsible for the delayed chondrocyte differentiation that is characteristic of this skeletal disorder. PTHrP protein distribution and gene expression levels were assessed by immunocytochemistry and reverse transcriptase-polymerase chain reaction, respectively. In growth plates of normal birds, PTHrP was found to be distributed throughout all maturational zones of the growth plate. In cartilage proximal to the TD lesion, PTHrP immunostaining and the level of PTHrP gene expression were similar to that observed in normal birds. In contrast, many chondrocytes within the centre of the TD lesion stained poorly for PTHrP and this was reflected in the lower levels of PTHrP mRNA detected in lesion cells. These results suggest that alterations in PTHrP distribution and gene expression are not primarily responsible for the delayed chondrocyte differentiation and hypertrophy noted in dyschondroplasia, but are a result of secondary changes due to the pathology of the condition. PMID:19184918

  2. Circulating parathyroid hormone and calcitonin in rats after spaceflight

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

    1992-01-01

    Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

  3. [A case of parathyroid adenoma with oxyphil cells].

    PubMed

    Enomoto, Katsuhisa; Sakurai, Kenichi; Amano, Sadao

    2014-11-01

    A 56-year-old woman who was undergoing dialysis for renal failure that occurred 4 years previously was identified with hypercalcemia and high levels of intact parathyroid hormone (iPTH), as observed on blood analysis results. Blood analysis also indicated high levels of Ca (12.7 mg/dL) and parathyroid hormone (PTH 1,280 ng/mL). Secondary hyperparathyroidism was suspected to be the cause of hypercalcemia. Cervical neck ultrasonography revealed a 13-× 4-mm hypoechoic mass in the lower left pole of the thyroid gland. Tc-99 metaiodobenzylguanidine (MIBG )imaging revealed aberrant accumulation at the lower region of the left accessory thyroid. Cervical neck computed tomography revealed a 12-mm mass at the inferior pole of the left thyroid gland. Considering the above observations, a diagnosis of lower left parathyroid adenoma was made. Lumpectomy was performed, and the final pathology report indicated oxyphilic adenoma. Chief cells are often observed in parathyroid adenoma, but, to our knowledge, this is the first case of a parathyroid adenoma with oxyphil cells. PMID:25731384

  4. The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report.

    PubMed

    Li, Qing; Pan, Jiemin; Luo, Quanyong; Wang, Yan; Bao, Yuqian; Jia, Weiping

    2015-06-01

    The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. PMID:26154096

  5. Image diagnosis of parathyroid glands in chronic renal failure

    SciTech Connect

    Takagi, H.; Tominaga, Y.; Uchida, K.; Yamada, N.; Morimoto, T.; Yasue, M.

    1983-07-01

    Twenty-two out of 31 patients with chronic renal failure and secondary hyperparathyroidism who underwent parathyroidectomy before operation underwent non-invasive image diagnosis of parathyroid glands by computed tomography (CT), scintigraphy with /sup 201/TlCl and /sup 99m/TcO/sup 4 +/, and/or ultrasonography. CT visualized 39 of 45 parathyroid glands (86.7%), weighing more than 500 mg. Scintigraphy with a subtraction method using a computer performed the diagnosis in 19 of 27 glands (70.4%). Ultrasonography detected 21 of 27 glands (77.8%). Image diagnosis was also useful in the postoperative follow-up study. The non-invasive image diagnosis of parathyroid glands in patients with chronic renal failure is thus valuable for 1) definite diagnosis of secondary hyperparathyroidism, 2) localization, and 3) diagnosis for effectiveness of conservative treatment.

  6. Presentation of parathyroid adenoma with genu valgum and thoracic deformities.

    PubMed

    Zil-E-Ali, Ahsan; Latif, Aiza; Rashid, Anam; Malik, Asim; Khan, Haseeb Ahmed

    2016-01-01

    Parathyroid adenoma is the main cause of primary hyperparathyroidism. It is usually asymptomatic and occurs more commonly in adults. It presents with raised parathormone (PTH) and Ca+ levels in serum. Its presentation in adolescence is rare. We report one such incidence of a 14 years old girl who presented with bone pains short stature, and generalized muscle wasting. She was found to have genu valgum at the knee joint, pectus carniatum, scoliosis and cystic changes in pelvis and calvarium. Biochemical investigations and parathyroid Tc-99mMIBI scan confirmed the diagnosis of a parathyroid adenoma. The gland was removed by parathyroidectomy. Till date 12 such cases are reported and none had thoracic, vertebral or calvarium involvement. PMID:26712192

  7. Experimental investigations on immunology of the parathyroid gland

    PubMed Central

    Lupulescu, A.; Potorac, E.; Pop, A.; Heitmanek, Constanta; Merculiev, Elena; Chisiu, N.; Oprisan, R.; Neacsu, C.

    1968-01-01

    Repeated inoculation of homologous parathyroid tissue in dogs induced isoimmune hypoparathyroidism, with all the characteristic biochemical and histopathological features and the presence of complement fixing antibodies in the serum. Disturbances of calcium and phosphorus metabolism were similar to, but less severe than, those observed in dogs with hypoparathyroidism induced by complete thyro-parathyroidectomy. Injection of rabbits with crude extracts of dog, rat, hog and human parathyroid or with bovine parathormone (PTH), each incorporated in Freund's adjuvant, resulted in the development of complement fixing and precipitating antibodies: these reacted with the corresponding tissue preparations, but did not show cross-reactivity. Antibodies were not detected in the serum of normal dogs or in control dogs inoculated with Freund's adjuvant alone. Study of the parathyroid glands by electron microscopy provided information on the mechanism of PTH secretion and synthesis in normal dogs and in those with hypoparathyroidism. ImagesFIG. 3FIG. 4-8FIG. 9FIG. 10-11 PMID:4968246

  8. Human chorionic gonadotropin measurements in parathyroid carcinoma

    PubMed Central

    Rubin, Mishaela R; Bilezikian, John P; Birken, Steven; Silverberg, Shonni J

    2010-01-01

    Objective Preoperatively, it is difficult to differentiate between parathyroid cancer (PtCa) and severe primary hyperparathyroidism (PHPT) due to a benign tumor. Human chorionic gonadotropin (hCG) is a tumor marker in trophoblastic and nontrophoblastic cancers and hyperglycosylated hCG is increased in hCG-secreting malignancies. We investigated whether hCG can distinguish PtCa cancer from benign disease and add prognostic information. Design Observational study. Methods Measurement of urinary hCG (total and malignant isoforms) and serum malignant hCG in 8 subjects with PtCa and in 18 subjects with PHPT (measurement of urine in ten and serum in eight). Results Total urinary hCG was normal in the benign PHPT control subjects (range: 0–17 fmol/mg Cr; nl < 50). In the PtCa subjects, three had normal total urinary hCG levels and survived complication free for at least 2 years; three had persistently elevated total urinary hCG levels (range: 217–1986 fmol/mg Cr) and sustained hip fracture (n = 3) and died (n = 2) within 3 and 6 months respectively; two had a rise in total urinary hCG and had hip fracture (n = 1) and died (n = 2) within 4 and 10 months respectively. Elevated urinary hCG was of the malignant hyperglycosylated isoform. Serum malignant hyperglycosylated hCG values in all of the cancer patients exceeded the maximal serum malignant hCG level of the PHPT subjects with benign disease (3.77 pmol/l). Conclusion hCG, especially itshyperglycosylated isoform, might add diagnostic and prognostic information in PtCa. Further studies would help to elucidate the role of hCG as a potential tumor marker in this disease. PMID:18625691

  9. Genetics and epigenetics of parathyroid hormone resistance.

    PubMed

    Bastepe, Murat

    2013-01-01

    End-organ resistance to the actions of parathyroid hormone (PTH) is defined as pseudohypoparathyroidism (PHP). Described originally by Fuller Albright and his colleagues in early 1940s, this rare genetic disease is subclassified into two types according to the nephrogenous response to the administration of biologically active PTH. In type I, the PTH-induced urinary excretion of both phosphate and cyclic AMP (cAMP) is blunted. In type II, only the PTH-induced urinary excretion of phosphate is blunted, while the cAMP response is unimpaired. Different subtypes of PHP type I have been described based on the existence of additional clinical features, such as resistance to other hormones and Albright's hereditary osteodystrophy, and underlying molecular defects. Genetic mutations responsible for the different subtypes of PHP type I involve the GNAS complex locus, an imprinted gene encoding the α-subunit of the stimulatory G protein (Gsα) and several other transcripts that are expressed in a parent-of-origin specific manner. Mutations in Gsα-coding GNAS exons cause PHP-Ia and, in some cases, PHP-Ic, while mutations that disrupt the imprinting of GNAS lead to PHP-Ib. PHP type II is less well characterized with respect to its molecular cause. Recently, however, mutations in PRKAR1A, a regulatory subunit of the cAMP-dependent protein kinase, have been identified in several cases of PTH and other hormone resistance and skeletal dysplasia that are considered to be affected by PHP type II due to unimpaired urinary excretion of cAMP following PTH administration. PMID:23392091

  10. A clinical audit of thallium-technetium subtraction parathyroid scans.

    PubMed Central

    Samanta, A.; Wilson, B.; Iqbal, J.; Burden, A. C.; Walls, J.; Cosgriff, P.

    1990-01-01

    Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work. PMID:2170959

  11. Spectrum of single photon emission computed tomography/computed tomography findings in patients with parathyroid adenomas

    PubMed Central

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Harisankar, Chidambaram Natrajan Balasubramanian; Bhattacharya, Anish; Bhadada, Sanjay

    2011-01-01

    Primary hyperparathyroidism results from excessive parathyroid hormone secretion. Approximately 85% of all cases of primary hyperparathyroidism are caused by a single parathyroid adenoma; 10–15% of the cases are caused by parathyroid hyperplasia. Parathyroid carcinoma accounts for approximately 3–4% of cases of primary disease. Technetium-99m-sestamibi (MIBI), the current scintigraphic procedure of choice for preoperative parathyroid localization, can be performed in various ways. The “single-isotope, double-phase technique” is based on the fact that MIBI washes out more rapidly from the thyroid than from abnormal parathyroid tissue. However, not all parathyroid lesions retain MIBI and not all thyroid tissue washes out quickly, and subtraction imaging is helpful. Single photon emission computed tomography (SPECT) provides information for localizing parathyroid lesions, differentiating thyroid from parathyroid lesions, and detecting and localizing ectopic parathyroid lesions. Addition of CT with SPECT improves the sensitivity. This pictorial assay demonstrates various SPECT/CT patterns observed in parathyroid scintigraphy. PMID:21969785

  12. Suppression of Parathyroid Hormone in a Patient with Severe Magnesium Depletion

    PubMed Central

    Fernandez, Isaac; Kochar, Tina

    2016-01-01

    Hypomagnesemia is often associated with coexisting electrolyte abnormalities like hypokalemia and hypocalcemia. Hypocalcemia has been shown to be secondary to hypoparathyroidism induced by hypomagnesemia. Here, we discuss a case of a patient with severe hypomagnesemia and associated hypocalcemia. A 38-year-old lady was admitted to the hospital for weakness of lower extremities and an eventual fall. The exam was significant for decreased motor strength and some paresthesias. The laboratory data was significant for hypomagnesemia, hypokalemia, and low parathyroid level in the face of hypocalcemia. After replacing magnesium, the parathyroid hormone levels normalized and led to eventual correction of calcium levels without any additional calcium replacement therapy. There was complete symptom resolution with correction of electrolyte abnormalities. This case highlights the importance of looking for all associated abnormalities in a patient with hypomagnesemia and starting the replacement therapy by first replacing the magnesium and then the others as needed. Replacing the magnesium alone may correct the hypoparathyroidism and eliminate the need for calcium replacement. PMID:27190662

  13. Dual phase MIBI scintigraphy in diagnosis of parathyroid adenoma followed by ultrasound guided percutaneous alcoholic ablation.

    PubMed

    Ahmad, Shakil; Jielani, Amjad Aziz Khan Asif; Khan, Kamran; Fatima, Tatheer; Zia, Nadeem; ud Duha, Mazhar; Samad, Abdul; Memon, Khalid

    2008-01-01

    Primary Hyperparathyroidism (HPT) is an inappropriate hyper secretion of parathyroid hormone (PTH). Primary HPT is caused by parathyroid adenoma in 80-85% of patients. Clinical manifestations are kidney stones, abdominal groans, painful bones, psychic moans, and fatigue overtones. Ultrasonography is widely used in suspected cases for localization of parathyroid adenoma. There is considerable intra-observer variation and it is difficult for ultrasound alone to differentiate parathyroid lesion form that of thyroid. Dual phase Tc-99m MIBI scinitigraphy for detection of parathyroid adenomas has sensitivity and specificity values ranging from 82% to 100% and from 89% to 100%, respectively. Percutaneous ethanol injection for parathyroid glands can be applied effectively in selected cases when surgery is unadvisable either for technical reasons (e.g., recurrence ofhyperplastic glands in the neck after subtotal surgery or intrathyroideal parathyroid tumors or the poor clinical state of the patient. PMID:19610543

  14. Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland

    PubMed Central

    Shiizaki, Kazuhiro; Hatamura, Ikuji; Negi, Shigeo; Nakazawa, Eiko; Tozawa, Ryoko; Izawa, Sayoko; Akizawa, Tadao; Kusano, Eiji

    2008-01-01

    Background. Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive secretion of parathyroid hormone (PTH) but also with changes in the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity and low contents of vitamin D and calcium-sensing receptors). The control of PTG hyperplasia is most important in the management of secondary hyperparathyroidism (SHPT), because the advanced stage of hyperplasia is considered irreversible. For the better control of the PTH level in dialysis patients with such advanced SHPT, percutaneous vitamin D injection therapy (PDIT) under ultrasonographic guidance was developed and various cellular changes caused by this treatment were also investigated using an animal model. Methods. The PTGs of Sprague–Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet, were treated with the direct injections of vitamin D agents, and cellular effects focusing the above-mentioned characters were investigated. Results. An adequacy of the direct injection technique into the rats’ PTGs and the successful effects of this treatment in various biochemical parameters were confirmed. Such characteristics of advanced SHPT were simultaneously improved; in particular, it was confirmed that this treatment may be effective in controlling PTG hyperplasia by, at least in part, apoptosis-induced cell death. Conclusions. A locally high level of vitamin D strongly may suppress PTH secretion and regress hyperplasia, which is involved in the induction of apoptosis in PTCs, based on the simultaneous improvements of cellular characters of advanced SHPT. The PTH control introduced by this treatment successfully ameliorated osteitis fibrosa (high bone turnover rate). PMID:25983973

  15. Cytologic findings of a clear cell parathyroid lesion.

    PubMed

    Papanicolau-Sengos, Antonios; Brumund, Kevin; Lin, Grace; Hasteh, Farnaz

    2013-08-01

    On fine-needle aspiration (FNA) biopsy, clear cell parathyroid lesions can be misdiagnosed as thyroid neoplasms, salivary gland neoplasms, paraganglioma, or even metastatic renal cell carcinoma. We report the clinicopathological, cytologic, and histologic findings of a clear cell parathyroid tumor in a 64-year-old HIV-positive patient. A computed tomography (CT) scan with contrast showed a heterogeneous and enhancing mass at the inferolateral aspect of the left thyroid lobe. FNA showed a cellular smear with many single and loosely clustered tumor cells with finely granular and vacuolated light-purple cytoplasm and central nuclei. Occasional microfollicular structures were noted. No colloid was seen. This FNA was misdiagnosed as a follicular neoplasm of the thyroid. Sections of the excised mass showed large polyhedral cells with well-defined cell membranes and clear cytoplasm with a small amount of eosinophilic granular material. These clear cells were positive for pancytokeratin and PTH immunohistochemical stains. These results favored a diagnosis of parathyroid Water Clear Cell Adenoma. This brief report highlights the cytologic findings of clear cell parathyroid lesions and their potential diagnostic pitfalls. PMID:22144114

  16. Upper alveolar brown tumor as initial presentation of parathyroid adenoma

    PubMed Central

    Hakeem, Arsheed Hussain; Hakeem, Imtiyaz Hussain; Wani, Fozia Jeelani

    2015-01-01

    Parathyroid adenoma usually presents with the signs and symptoms of hypercalcemia due to hyperparathyroidism. Brown's tumor is the late clinical consequence of untreated hyperparathyroidism and is rarely seen now-a-days due to improved screening biochemical tests. These tumors are characterized by high orthoclastic activity and bone resorption. These are usually located in the pelvis, ribs, clavicles, and extremities. This manuscript highlights a rare presentation of brown's tumor of upper alveolus in a 35-year-old female with a previously undiagnosed case of hyperparathyroidism due to a parathyroid adenoma. Blood analysis depicted high levels of serum calcium and parathyroid hormone. The patient was subjected to selective left lower parathyroidectomy and will receive follow-up to prevent further developments of the disease. Clinicians should be aware of such rare presentation of parathyroid adenomas so that unnecessary extensive surgery of brown's tumor is avoided. This case also highlights the need of detailed work up to arrive at an exact diagnosis and direct surgical intervention to the adenoma rather the secondary manifestation of the disease. PMID:27390503

  17. Effect of lithium maintenance therapy on thyroid and parathyroid function.

    PubMed Central

    Kusalic, M; Engelsmann, F

    1999-01-01

    OBJECTIVES: To assess changes induced by lithium maintenance therapy on the incidence of thyroid, parathyroid and ion alterations. These were evaluated with respect to the duration of lithium therapy, age, sex, and family history (whether or not the patient had a first-degree relative with thyroid disease). DESIGN: Prospective study. SETTING: Affective Disorders Clinic at St. Mary's Hospital, Montreal. PATIENTS: One hundred and one patients (28 men and 73 women) with bipolar disorder receiving lithium maintenance therapy ranging from 1 year's to 32 years' duration. The control group consisted of 82 patients with no psychiatric or endocrinological diagnoses from the hospital's out-patient clinics. OUTCOME MEASURES: Laboratory analyses of calcium, magnesium and thyroid-stimulating hormone levels performed before beginning lithium therapy and at biannual follow-up. RESULTS: Hypothyroidism developed in 40 patients, excluding 8 patients who were hypothyroid at baseline. All patients having first-degree relatives affected by thyroid illness had accelerated onset of hypothyroidism (3.7 years after onset of lithium therapy) compared with patients without a family history (8.6 years after onset of lithium therapy). Women over 60 years of age were more often affected by hypothyroidism than women under 60 years of age (34.6% versus 31.9%). Magnesium levels in patients on lithium treatment were unchanged from baseline levels. After lithium treatment, calcium levels were higher than either baseline levels or control levels. Thus, lithium treatment counteracted the decrease in plasma calcium levels associated with aging. CONCLUSIONS: Familial thyroid illness is a risk factor for hypothyroidism and hypercalcemia during lithium therapy. PMID:10354657

  18. Impact of hybrid SPECT/CT imaging on the detection of single parathyroid adenoma

    NASA Astrophysics Data System (ADS)

    Morrison, Antony; Brennan, Patrick C.; Reed, Warren; Pietrzyk, Mariusz; Schembri, Geoff; Bailey, Elizabeth; Roach, Paul; Evanoff, Michael; Kench, Peter L.

    2011-03-01

    Objective: The aim of this investigation is to determine the impact of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) on the detection of parathyroid adenoma. Materials and methods: 16 patients presented with suspected parathyroid adenoma localised within the neck. All patients were injected with Tc-99m sestamibi and were scanned with a GE Infinia Hawkeye SPECT/CT. There were six negative and ten positive confirmed cases. Five expert radiologists specializing in nuclear medicine were asked to report on the 16 planar and SPECT data sets and were then asked to report on the same randomly ordered data sets with the addition of CT. Receiver operating characteristic (ROC) analysis was performed using the Dorfman-Berbaum-Metz multireadermulticase methodology and sensitivity and specificity values were generated. A significance level of p <= 0.05 was set for all comparisons. Results: ROC analysis demonstrated an AUC of 0.64 and 0.69 for SPECT and SPECT/CT respectively (p = 0.31). Mean sensitivity scores increased from 0.64 to 0.80 (p = 0.17) and specificity scores decreased from 0.57 to 0.40 (p = 0.17) with the addition of the CT data. Conclusion: This preliminary investigation suggests that extra CT information may increase lesion detection as well as false positive rates for SPECT-based investigations of a single parathyroid adenoma. However the difference in diagnostic efficacy between the two groups was not found to be statistically significant therefore requiring further investigation. These findings have implications beyond the clinical situation described here.

  19. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

  20. An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH) D]. In children and adolescents, the relationship between serum 25(OH) D and PTH is less clear, and most studies reporting a relationship are der...

  1. Parathyroid autotransplantation during total thyroidectomy. Results of a retrospective study.

    PubMed

    Tartaglia, Francesco; Blasi, Sara; Giuliani, Alessandro; Merola, Raffaele; Livadoti, Giada; Krizzuk, Dimitri; Tortorelli, Giovanni; Tromba, Luciana

    2016-04-01

    Authors analyze their experience of parathyroid autotransplantation during total thyroidectomy, with the purpose of seeing whether this practice influenced the rate of postoperative hypocalcemia and/or hypoparathyroidism. We identified three groups of patients: group A, consisting of 57 patients, underwent parathyroid autotransplantation during total thyroidectomy; group B consisting of 87 patients not submitted to intraoperative autotransplantation in whom, as an incidental finding, a parathyroid gland was detected in the surgical specimen; group C consisted of 100 patients who did not undergo autotransplantation and whose surgical specimens were not found to contain parathyroid glands. The three groups were compared for sex and age as well as for a series of clinical and laboratory parameters on the first three postoperative days and at six months after surgery. The rate of permanent hypoparathyroidism was 3.5% in Group A, 3.45% in Group B, and 1% in Group C. Multivariate analysis revealed that all three groups showed postoperative recovery of calcium levels, although the rate and extent of this recovery differed between them. The control group showed a more rapid and more complete recovery of serum calcium values compared with Groups A and B. Calcium recovery in Groups A and B was comparable, in terms of both rate and extent. The same pattern of results emerged for the iPTH values. The analysis of the data showed that there were no significant differences in the analyzed parameters between Groups A and B. This suggests that parathyroid autotransplantation does not influence the rate of postoperative hypocalcemia and/or hypoparathyroidism. PMID:26708849

  2. Membrane raft association is a determinant of plasma membrane localization

    PubMed Central

    Diaz-Rohrer, Blanca B.; Levental, Kandice R.; Simons, Kai; Levental, Ilya

    2014-01-01

    The lipid raft hypothesis proposes lateral domains driven by preferential interactions between sterols, sphingolipids, and specific proteins as a central mechanism for the regulation of membrane structure and function; however, experimental limitations in defining raft composition and properties have prevented unequivocal demonstration of their functional relevance. Here, we establish a quantitative, functional relationship between raft association and subcellular protein sorting. By systematic mutation of the transmembrane and juxtamembrane domains of a model transmembrane protein, linker for activation of T-cells (LAT), we generated a panel of variants possessing a range of raft affinities. These mutations revealed palmitoylation, transmembrane domain length, and transmembrane sequence to be critical determinants of membrane raft association. Moreover, plasma membrane (PM) localization was strictly dependent on raft partitioning across the entire panel of unrelated mutants, suggesting that raft association is necessary and sufficient for PM sorting of LAT. Abrogation of raft partitioning led to mistargeting to late endosomes/lysosomes because of a failure to recycle from early endosomes. These findings identify structural determinants of raft association and validate lipid-driven domain formation as a mechanism for endosomal protein sorting. PMID:24912166

  3. Complete Tumor Resection for a Hepatocellular Carcinoma Secreting Parathyroid Hormone-related Peptide.

    PubMed

    Kim, Eun Kyoung; Kim, Jin Su; Shin, Ki Chul; Lee, Gil Tae; Han, Chul Ju; Kim, Sang Beom; Ku, Yun Hyi

    2015-08-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in Korea. Diverse paraneoplastic syndromes can occur in patients with HCC, but parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia is uncommon. Hypercalcemia due to PTH or particularly PTH-rP-secreting HCC is associated with poor outcomes. We report a 71-year-old man who presented with symptoms of vague abdominal discomfort, somnolence, lethargy, nausea, vomiting, and weight loss. Imaging studies revealed a large HCC without metastasis. The laboratory findings showed elevated serum calcium level, low intact parathyroid hormone (iPTH) level and elevated PTH-rP level. These results led to a diagnosis of a PTH-rP-secreting HCC and paraneoplastic hypercalcemia. After emergency management of the hypercalcemia, the patient underwent an extended right hemihepatectomy with cholecystectomy. One year after the surgery, he is alive with normal calcium, PTH-rP, and iPTH levels. This case demonstrates that the rare phenomenon of life-threatening hypercalcemia caused by HCC should not be overlooked. These symptoms offer a good opportunity to diagnose HCC early. Radical tumor resection makes it possible to cure patients with PTH-rP-secreting HCC. PMID:26289247

  4. Isolation and characterization of the human parathyroid hormone-like peptide gene

    SciTech Connect

    Mangin, M.; Ikeda, K.; Dreyer, B.E.; Broadus, A.E. )

    1989-04-01

    A parathyroid hormone-like peptide (PTH-LP) has recently been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The peptide appears to be encoded by a single-copy gene that gives rise to multiple mRNAs that are heterogeneous at both their 5{prime} and their 3{prime} ends. Alternative RNA splicing is responsible for the 3{prime} heterogeneity and results in mRNAs encoding three different peptides, each with a unique C terminus. The authors have isolated and characterized the human PTHLP gene. The gene is a complex transcriptional unit spanning more than 12 kilobases of DNA and containing six exons. Two 5{prime} exons encode distinct 5{prime} untranslated regions and are separated by a putative promoter element, indicating that the gene either has two promoters or is alternatively spliced from a single promoter upstream of the first exon. The middle portion of the PTHLP gene, comprising exons 2-4, has an organizational pattern of introns and exons identical to that of the parathyroid hormone gene, consistent with a common ancestral origin of these two genes. Exon 4 of the PTHLP gene encodes the region common to all three peptides and the C terminus of the shortest peptide, and exons 5 and 6 encode the unique C termini of the other two peptides. Northern analysis of mRNAs from four human tumors of different histological types reveals the preferential use of 3{prime} splicing patterns of individual tumors.

  5. Bisphosphonates, vitamin D, parathyroid hormone, and osteonecrosis of the jaw. Could there be a missing link?

    PubMed Central

    Leizaola-Cardesa, Ignacio-Osoitz; Aguilar-Salvatierra, Antonio; Gonzalez-Jaranay, Maximino; Moreu, Gerardo; Sala-Romero, María-José

    2016-01-01

    It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug. Key words:Bisphosphonate-related osteonecrosis of the jaw, vitamin D, parathyroid hor PMID:26827062

  6. Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

    PubMed Central

    Delmez, J A; Tindira, C; Grooms, P; Dusso, A; Windus, D W; Slatopolsky, E

    1989-01-01

    Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels. PMID:2703535

  7. Inhibition of parathyroid hormone-related protein release by extracellular calcium in dispersed cells from human parathyroid hyperplasia secondary to chronic renal failure and adenoma.

    PubMed Central

    Matsushita, H.; Hara, M.; Honda, K.; Kuroda, M.; Usui, M.; Nakazawa, H.; Hara, S.; Shishiba, Y.

    1995-01-01

    The relationship between parathyroid hormone-related protein (PTHrP) release from parathyroid cells and extracellular calcium ion concentration was investigated in three cases of parathyroid hyperplasia secondary to chronic renal failure and in four cases of parathyroid adenoma. Amounts of PTHrP released from individual parathyroid cells dispersed from surgical specimens were estimated by cell immunoblot assay. Parathyroid cells from both hyperplasias and adenomas showed significant suppression in the release of PTHrP with increase in extracellular calcium ions, but the amounts of PTHrP released from adenoma cells were significantly larger than from hyperplasia cells. The maximal value for PTHrP released within 120 minutes from adenoma cells was 2.91 +/- 2.11 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 1.32 +/- 0.35 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). On the other hand, the maximal value for PTHrP released from hyperplasia cells was 1.79 +/- 1.56 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 0.32 +/- 0.19 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). These results demonstrate actual release of PTHrP from abnormal parathyroid tissues into the extracellular space with the response to extracellular calcium ions depending on the cell status. Given the lack of definite histological criteria to differentiate between hyperplasias and adenomas in the parathyroid gland, the presently demonstrated significant difference in the ability to release PTHrP is important in pointing to parathyroid hyperplasia secondary to chronic renal failure as a distinct pathological entity separate from parathyroid adenoma. Images Figure 3 PMID:7778690

  8. Chaos as a social determinant of child health: Reciprocal associations?

    PubMed

    Kamp Dush, Claire M; Schmeer, Kammi K; Taylor, Miles

    2013-10-01

    This study informs the social determinants of child health by exploring an understudied aspect of children's social contexts: chaos. Chaos has been conceptualized as crowded, noisy, disorganized, unpredictable settings for child development (Evans, Eckenrode, & Marcynyszyn, 2010). We measure chaos at two levels of children's ecological environment - the microsystem (household) and the mesosystem (work-family-child care nexus) - and at two points in early childhood (ages 3 and 5). Using data from the Fragile Families and Child Wellbeing Study (N = 3288), a study of predominantly low-income women and their partners in large US cities, we develop structural equation models that assess how maternal-rated child health (also assessed at ages 3 and 5) is associated with latent constructs of chaos, and whether there are important reciprocal effects. Autoregressive cross-lagged path analysis suggest that increasing chaos (at both the household and maternal work levels) is associated with worse child health, controlling for key confounders like household economic status, family structure, and maternal health status. Child health has little effect on chaos, providing further support for the hypothesis that chaos is an important social determinant of child health in this sample of relatively disadvantaged children. This suggests child health may be improved by supporting families in ways that reduce chaos in their home and work/family environments, and that as researchers move beyond SES, race, and family structure to explore other sources of health inequalities, chaos and its proximate determinants may be a promising avenue for future research. PMID:23541250

  9. Parathyroid Hormone and Physical Exercise: a Brief Review

    PubMed Central

    Bouassida, Anissa; Latiri, Imed; Bouassida, Semi; Zalleg, Dalenda; Zaouali, Monia; Feki, Youssef; Gharbi, Najoua; Zbidi, Abdelkarim; Tabka, Zouhair

    2006-01-01

    Parathyroid hormone (PTH) is the major hormone regulating calcium metabolism and is involved in both catabolic and anabolic actions on bone. Intermittent PTH exposure can stimulate bone formation and bone mass when PTH has been injected. In contrast, continuous infusion of PTH stimulates bone resorption. PTH concentration may be affected by physical exercise and our review was designed to investigate this relationship. The variation in PTH concentration appears to be influenced by both exercise duration and intensity. There probably exists a stimulation threshold of exercise to alter PTH. PTH regulation is also influenced by the initial bone mineral content, age, gender, training state, and other hormonal and metabolic factors (catecholamines, lactic acid and calcium concentrations). Key Points Physical exercise can improve PTH secretion. Parathyroid hormone has both anabolic and catabolic effects on bone: intermittent treatment of PTH is anabolic whereas continuous treatment is catabolic. PMID:24353453

  10. [Unusual location of a parathyroid adenoma: the carotid sheath].

    PubMed

    Smayra, T; Abi Khalil, S; Abboud, B; Halabi, G; Slaba, S

    2006-01-01

    We report the imaging features of an occult parathyroid adenoma with unusual location in the carotid sheath. Our patient presented with primary hyperparathyroidism. Following negative neck ultrasound and scintigraphy, exploratory neck dissection with partial thyroidectomy was performed twice over a 2 day period without biological response. Cervical and mediastinal CT and MRI were performed with no result. Digital angiography showed a tumoral blush supplied by the left inferior thyroid artery and located in close contact with the carotid artery. Venous sampling of the neck confirmed the left location of the adenoma and a third surgical intervention found the adenoma embedded in the left carotid sheath. This is an unusual case of parathyroid adenoma that necessitated the use of several imaging techniques. PMID:16415782

  11. Recombinant production of TEV cleaved human parathyroid hormone.

    PubMed

    Audu, Christopher O; Cochran, Jared C; Pellegrini, Maria; Mierke, Dale F

    2013-08-01

    The parathyroid hormone, PTH, is responsible for calcium and phosphate ion homeostasis in the body. The first 34 amino acids of the peptide maintain the biological activity of the hormone and is currently marketed for calcium imbalance disorders. Although several methods for the production of recombinant PTH(1-34) have been reported, most involve the use of cleavage conditions that result in a modified peptide or unfavorable side products. Herein, we detail the recombinant production of (15) N-enriched human parathyroid hormone, (15) N PTH(1-34), generated via a plasmid vector that gives reasonable yield, low-cost protease cleavage (leaving the native N-terminal serine in its amino form), and purification by affinity and size exclusion chromatography. We characterize the product by multidimensional, heteronuclear NMR, circular dichroism, and LC/MS. PMID:23794508

  12. Open mini-incision parathyroidectomy for solitary parathyroid adenoma.

    PubMed

    Kelly, Ciaran W P; Eng, Chee-Yean; Quraishi, M Shahed

    2014-03-01

    Parathyroid surgery is the acceptable definitive treatment for primary hyperparathyroidism (pHPT) due to parathyroid adenoma. Open mini-incision parathyroidectomy (O-MIP) has an excellent cure rate and minimal morbidity. We aim to demonstrate the safety, efficacy and subjective patient satisfaction of O-MIP and investigate the accuracy of pre-operative radiological localisation in relation to operative findings. A retrospective review of patients who underwent O-MIP for pHPT due to solitary parathyroid adenoma from April 2006 to August 2012 was performed. All patients were initially investigated by an endocrinologist to confirm pHPT with pre-operative localisation imaging using ultrasound scan (USS) and 99mTc-sestamibi (MIBI). One hundred and fifty consecutive patients were included with a median age of 62 years. Pre-operative USS and MIBI scans were concordant in 71 % of cases. In combined modality (USS and MIBI), localisation was 94.8 % accurate. There was 95.5 % identification of parathyroid tissue confirmed by intra-operative frozen section. Ninety-one percent of patients were treated as a day case. The median operative time was 60 min. The mean pre-operative calcium level was 2.98 mmol/l, and the short-to-medium term mean calcium level was 2.49 (Paired t test, p < 0.001). There was no significant complication. O-MIP confers significant advantages over the traditional gold standard treatment of bilateral neck exploration. Accurate localisation is the key to successful O-MIP. In experienced hands, ultrasound and MIBI may be the only pre-operative investigations required for accurate localisation. PMID:23653305

  13. Undescended parathyroid adenomas as cause of persistent hyperparathyroidism

    PubMed Central

    Mateu, Germán; Lorente-Poch, Leyre; Sancho, Juan J.; Sitges-Serra, Antonio

    2015-01-01

    Background Undescended glands are a rare cause of primary and secondary hyperparathyroidism (HPT), but they are more common, however, among patients with recurrent HPT or those who have undergone a failed initial cervical exploration. The currently development of more precise noninvasive imaging techniques has improved the results of preoperative diagnosis of these ectopic lesions. Methods The operative reports of patients undergoing parathyroidectomy at our institution were reviewed to identify patients with an undescended parathyroid gland adenomas. Demographic, clinical, imaging and surgical variables were recorded. Results Three patients were included: 2/598 parathyroidectomies performed for primary HPT and 1/93 performed for secondary HPT. One case is presented as jaw tumor syndrome (JTS). All the patients had undergone at least one operation before the definitive focused surgery and represented 6% of our parathyroid reoperations. No significant complications and no recurrences were observed in the long-term follow up. Conclusions Accurate preoperative localization of these lesions was possible with noninvasive studies. High cure rate is possible through selective approach when accurate preoperative localization. Thorough knowledge of parathyroid embryology and meticulous surgical technique are essential, particularly in patients with previous unsuccessful explorations. PMID:26312215

  14. Subclinical and asymptomatic parathyroid disease: implications of emerging data.

    PubMed

    Macfarlane, David P; Yu, Ning; Leese, Graham P

    2013-12-01

    Primary hyperparathyroidism, a disorder in which there is a tendency for hypercalcaemia caused by autonomous overproduction of parathyroid hormone, is common, especially in postmenopausal women. Although parathyroidectomy is indicated for symptomatic patients, most individuals with the disorder are asymptomatic and without classic complications, such as renal stones and osteoporosis, at diagnosis. Consensus guidelines suggest which individuals might be suitable for medical follow-up rather than parathyroidectomy, but there are no long-term randomised controlled trials to support the safety of medical surveillance, and some patients progress with time. Data from observational studies suggest that cardiovascular morbidity and mortality are increased in patients with primary hyperparathyroidism, and might be predicted by parathyroid hormone concentrations, even in individuals with asymptomatic primary hyperparathyroidism. Whether parathyroidectomy improves cardiovascular outcomes in patients with asymptomatic primary hyperparathyroidism is unproven, but data suggest that surgery decreases fracture risk and might improve neuropsychological symptoms. Studies also show that patients with normocalcaemic (subclinical) hyperparathyroidism and hypoparathyroidism have a low risk of progression to overt disease, but their long-term risks are not defined. In this Review, we explore the increasing range of asymptomatic parathyroid disorders, focusing on current evidence about their natural history and potential complications, with a particular emphasis on primary hyperparathyroidism. PMID:24622418

  15. Ectopic Intrathymic Parathyroid adenoma demonstrated on Tc-99m Sestamibi SPECT-CT.

    PubMed

    Usmani, S; Oteifa, M; Abu Huda, F; Javaid, A; Amanguno, H G; Al Kandari, F

    2016-05-01

    Intrathymic parathyroid adenoma is a rare cause of primary hyperparathyroidism. In this case, Tc-99m Sestamibi SPECT-CT successfully localized abnormal tracer uptake in the mediastinum with corresponding low density lesion on CT images suggestive of mediastinal parathyroid adenoma which late on confirmed on histopathology. After the median sternotomy a large intrathymic parathyroid adenoma was identified and excised. With the help of gamma probe the surgeons detect the lesion early and with more confidence as well as reducing the total operation time. Tc-99m Sestamibi SPECT-CT scintigraphy and gamma probe localization is recommended for preoperative and intra operative localization of ectopic parathyroid adenomas. PMID:27250890

  16. PSYCHOLOGICAL AND PSYCHOSOCIAL DETERMINANTS OF MUSCULOSKELETAL PAIN AND ASSOCIATED DISABILITY

    PubMed Central

    Vargas-Prada, Sergio; Coggon, David

    2015-01-01

    Although much attention has been given to the physical determinants of common musculoskeletal complaints such as back and arm pain, research points to a stronger influence of psychological factors. Multiple studies have implicated poor mental health and somatisation (a tendency to worry about common somatic symptoms) in the incidence and chronicity of musculoskeletal pain and associated disability. Also important are adverse beliefs about the prognosis of such disorders, and about the role of physical activity in their development and persistence. Differences in societal beliefs may have contributed to major variation in the prevalence of disabling musculoskeletal pain that has been observed between countries and in the same countries over time. Psychosocial aspects of work have also been linked with musculoskeletal pain, although relative risks have generally been smaller. There is a need to take account of psychological factors in the clinical management of patients with back, neck and arm pain. PMID:26612236

  17. 11C-Methionine positron emission tomography-computed tomography in localization of methoxyisobutyl isonitrile negative ectopic parathyroid adenoma

    PubMed Central

    Seniaray, Nikhil; Sharma, Harshul; Arbind, Arpana; Jaimini, Abhinav; D’souza, Maria; Saw, Sanjeev; Hazari, Puja Panwar; Mishra, A. K.; Sharma, Rajnish; Mondal, Anupam

    2016-01-01

    Primary hyperparathyroidism is caused by parathyroid adenomas in 85% of the cases. Since parathyroid adenomas are known for their ectopic location, presurgical localization of the suspected site of adenoma is desirable. However, current imaging modalities are not always successful in localizing ectopic parathyroid adenomas. The aim of this case report is to show that 11C-methionine positron emission tomography could accurately localize ectopic parathyroid adenomas in patients in whom conventional imaging had failed or is inconclusive. PMID:26917896

  18. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  19. Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American-Diabetes Heart Study.

    PubMed

    Palmer, Nicholette D; Divers, Jasmin; Lu, Lingyi; Register, Thomas C; Carr, J Jeffrey; Hicks, Pamela J; Smith, S Carrie; Xu, Jianzhao; Judd, Suzanne E; Irvin, Marguerite R; Gutierrez, Orlando M; Bowden, Donald W; Wagenknecht, Lynne E; Langefeld, Carl D; Freedman, Barry I

    2016-06-01

    Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American-Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2 (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P=1.38×10(-82)) and novel (rs12741813 and rs10863774 with VDBP, P<6.43×10(-5)) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits. PMID:27032714

  20. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Schnoes, Heinrich K.; Deluca, Hector F.; Phelps, Mary E.; Klein, Robert F.

    1988-01-01

    The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

  1. Parathyroid Lipoadenoma: a Clinicopathological Diagnosis and Possible Trap for the Unaware Pathologist.

    PubMed

    Hyrcza, Martin D; Sargın, Pınar; Mete, Ozgur

    2016-03-01

    The authors present clinicopathological features of parathyroid lipoadenoma in a 48-year-old woman who presented with symptomatic primary hyperparathyroidism manifesting with pathological fractures and osteoporosis. Preoperative sestamibi scan failed to localize the source of her disease. Exploratory surgery identified an enlarged parathyroid gland with abundant fat tissue. The significant drop of intraoperative serum parathyroid hormone after the removal of this gland and postoperative biochemical cure justified the presence of a single gland disease presenting as parathyroid lipoadenoma. From an educational perspective, the presented case emphasizes why the historical approach to parathyroid proliferations by assessing alone the ratio of parenchymal cells to adipocytes is not a reliable method in the diagnostic evaluation of parathyroid disease. While the accurate size and weight of a parathyroid gland are defining parameters of an abnormal gland, intraoperative and postoperative biochemical workup distinguishes uniglandular disease (adenoma) from multiglandular disease (hyperplasia). The authors also provide a brief review of the previously published cases of parathyroid lipoadenomas to highlight their clinicopathological characteristics of relevance to surgical pathologists. PMID:26585863

  2. Sleeping Parathyroid Tumor: Rapid Hyperfunction after Removal of the Dominant Tumor

    PubMed Central

    Simonds, William F.; Weinstein, Lee S.; Collins, Michael T.; Kebebew, Electron; Nilubol, Naris; Phan, Giao Q.; Libutti, Steven K.; Remaley, Alan T.; Van Deventer, Manuel; Marx, Stephen J.

    2012-01-01

    Context: Due to frequent multiplicity of tumors in multiple endocrine neoplasia type 1, it may be difficult to decide when to stop a parathyroid exploration. A fall of intraoperative serum PTH by a certain percentage during parathyroid surgery is often used as one criterion for ending the operation. Results: We report two patients with primary hyperparathyroidism due to multiple endocrine neoplasia type 1 who had their first parathyroidectomy at the National Institutes of Health. In both cases, two and a half glands were removed, an extensive search was done for an occult parathyroid tumor, and intraoperative PTH decreased markedly to the lower limits of normal, suggesting a successful operation. Despite this, both patients became hypercalcemic within 3 d after the operation and showed persistent primary hyperparathyroidism. Detailed findings suggest the following course: chronic hypercalcemia had caused near total suppression of PTH secretion by an undiscovered parathyroid tumor (sleeping parathyroid tumor). When the hypercalcemia decreased after surgery due to the removal of the dominant parathyroid tumor(s), the abnormal yet previously suppressed tumor rapidly began to oversecrete PTH and thus caused postoperative hypercalcemia. Conclusions: Even a fall of the intraoperative PTH to the lower limits of the normal range cannot guarantee that removal of all parathyroid tumors has been complete in cases with multiple tumors. These findings likely reflect strikingly differing PTH secretory functions among distinct tumors in the same patient, with hypercalcemia at least from a dominant tumor suppressing PTH secretion by one or more other parathyroid tumors. PMID:22508712

  3. Needle aspirate PTH in diagnosis of primary hyperparathyroidism due to intrathyroidal parathyroid cyst

    PubMed Central

    Dutta, Deep; Selvan, Chitra; Kumar, Manoj; Datta, Saumik; Das, Ram Narayan; Ghosh, Sujoy; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2013-01-01

    Summary Parathyroid cysts are rare (0.8–3.41% of all parathyroid lesions) and usually arise secondary to cystic degeneration of parathyroid adenomas. Intrathyroidal parathyroid cysts are extremely rare with only three cases reported till date. We present a 24-year-old female with clinical and biochemical features of primary hyperparathyroidism (PHPT; Ca2 +: 12.1 mg/dl; intact parathyroid hormone (iPTH): 1283 pg/ml) and poor radiotracer uptake with minimal residual uptake in the left thyroid lobe at 2 and 4 h on Tc99m sestamibi imaging. Neck ultrasonography (USG) revealed 0.6×1 cm parathyroid posterior left lobe of thyroid along with 22×18 mm simple thyroid cyst. USG-guided fine-needle aspiration (FNA) and needle tip iPTH estimation (FNA-iPTH) from parathyroid lesion was inconclusive (114 pg/ml), necessitating FNA of thyroid cyst, which revealed high iPTH (3480 pg/ml) from the aspirate. The patient underwent a left hemithyroidectomy. A >50% drop in serum iPTH 20 min after left hemithyroidectomy (29.4 pg/ml) along with histopathology suggestive of intrathyroidal cystic parathyroid adenoma (cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion surrounded by normal thyroid follicles) confirmed that the parathyroid cyst was responsible for PHPT. This report highlights the importance of FNA-iPTH in localizing and differentiating a functional parathyroid lesion from nonfunctional tissue in PHPT. Learning points Fine-needle aspiration from suspected parathyroid lesion and needle tip iPTH (FNA-iPTH) estimation from the saline washing has an important role in localizing primary hyperparathyroidism (PHPT).FNA-iPTH estimation may help in differentiating functional from nonfunctional parathyroid lesion responsible for PHPT.iPTH estimation from aspirate of an intrathyroid cyst is helpful in differentiating intrathyroidal parathyroid cyst from thyroid cyst. PMID:24616763

  4. Parathyroid Adenoma Completely Impacted within the Thyroid Gland: A Case Report.

    PubMed

    Mirhosaini, Sayed Mahmoud; Amani, Soroush; Fereidani, Rana

    2016-06-01

    Ectopic parathyroid adenoma can be seen in various locations. Sometimes ultrasound and even fine needle aspiration studies cannot distinguish this lesion from thyroid lesions. A 29-year-old woman with a prominent nodule of left thyroid lobe was referred to surgical department. Thyroid function test were normal. She had no family history of parathyroid disease, other endocrine disease, and any other malignancies and had received no radiation. Ultrasonography revealed a solid and hypoechoic mass, 25x20 mm in size, with a regular shape and contour without calcification in the inferior of left lobe of the thyroid gland. For definite diagnosis, immunohistochemistry study of the lesion with three markers was done. Finally, PTH marker was positive in cytoplasms of cells so parathyroid adenoma was confirmed. Fine needle aspiration of the nodule was suspicious for follicular neoplasm; however, postoperative histopathology and immunohistochemistry revealed a parathyroid adenoma. Ultrasonography may be helpful to identify localized thyroid lesions especially in parathyroid adenoma. PMID:27504318

  5. Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids

    SciTech Connect

    Wortman, J.A.; Alavi, A.; Attie, M.; Yudd, A.P.; Johnston, S.A.; Greenberg, J.

    1987-09-01

    We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-(1-/sup 14/C)leucine and L-(guanido-/sup 14/C)arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the (/sup 14/C)leucine and (/sup 14/C)arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

  6. A rare case of giant parathyroid adenoma presenting with recurrent episodes of pancreatitis.

    PubMed

    Krishnamurthy, Arvind; Raghunandan, Gorantlu Chowdappa; Ramshankar, Vijayalakshmi

    2016-01-01

    Parathyroid adenomas are usually small in size; (weighing 70 mg-1 g) those weighing more than 2-3 g are classified as giant parathyroid adenomas. Giant parathyroid adenomas are in fact rarely encountered among patients with primary hyperparathyroidism. They are believed to have distinct clinical and biochemical features related to specific genomic alterations. We chanced to manage a unique and possibly the first case of giant parathyroid adenoma (6 cm diameter and weighing 20 g) presenting with recurrent episodes of pancreatitis and discuss its surgical management with an added emphasis on the role of nuclear imaging in its preoperative localization. Our case demonstrates that clinicians should have a high index of suspicion of primary hyperparathyroidism in patients presenting with recurrent episodes of pancreatitis. Timely diagnosis, appropriate preoperative localization techniques, which would include a parathyroid scintigraphy and a focused surgical intervention are crucial to resolve complications and improve outcomes. PMID:26917892

  7. Parathyroid Adenoma Completely Impacted within the Thyroid Gland: A Case Report

    PubMed Central

    Mirhosaini, Sayed Mahmoud; Fereidani, Rana

    2016-01-01

    Ectopic parathyroid adenoma can be seen in various locations. Sometimes ultrasound and even fine needle aspiration studies cannot distinguish this lesion from thyroid lesions. A 29-year-old woman with a prominent nodule of left thyroid lobe was referred to surgical department. Thyroid function test were normal. She had no family history of parathyroid disease, other endocrine disease, and any other malignancies and had received no radiation. Ultrasonography revealed a solid and hypoechoic mass, 25x20 mm in size, with a regular shape and contour without calcification in the inferior of left lobe of the thyroid gland. For definite diagnosis, immunohistochemistry study of the lesion with three markers was done. Finally, PTH marker was positive in cytoplasms of cells so parathyroid adenoma was confirmed. Fine needle aspiration of the nodule was suspicious for follicular neoplasm; however, postoperative histopathology and immunohistochemistry revealed a parathyroid adenoma. Ultrasonography may be helpful to identify localized thyroid lesions especially in parathyroid adenoma. PMID:27504318

  8. A rare case of giant parathyroid adenoma presenting with recurrent episodes of pancreatitis

    PubMed Central

    Krishnamurthy, Arvind; Raghunandan, Gorantlu Chowdappa; Ramshankar, Vijayalakshmi

    2016-01-01

    Parathyroid adenomas are usually small in size; (weighing 70 mg–1 g) those weighing more than 2–3 g are classified as giant parathyroid adenomas. Giant parathyroid adenomas are in fact rarely encountered among patients with primary hyperparathyroidism. They are believed to have distinct clinical and biochemical features related to specific genomic alterations. We chanced to manage a unique and possibly the first case of giant parathyroid adenoma (6 cm diameter and weighing 20 g) presenting with recurrent episodes of pancreatitis and discuss its surgical management with an added emphasis on the role of nuclear imaging in its preoperative localization. Our case demonstrates that clinicians should have a high index of suspicion of primary hyperparathyroidism in patients presenting with recurrent episodes of pancreatitis. Timely diagnosis, appropriate preoperative localization techniques, which would include a parathyroid scintigraphy and a focused surgical intervention are crucial to resolve complications and improve outcomes. PMID:26917892

  9. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma

    PubMed Central

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad

    2015-01-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology. PMID:26813941

  10. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma.

    PubMed

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad; Bahadoram, Mohammad

    2015-12-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology. PMID:26813941

  11. Responsiveness of neoplastic and hyperplastic parathyroid tissues to calcium in vitro.

    PubMed Central

    Habener, J F

    1978-01-01

    Secretory and biosynthetic responses of adenomatous, carcinomatous, and hyperplastic parathyroid tissues to variable concentrations of extracellular calcium were assessed in vitro. Tissues, obtained at the time of parathyroidectomy, were incubated for 4 h in media containing radioactive amino acids and varying (0.5-5.0 mM) concentrations of calcium. Amounts of newly synthesized and total parathyroid hormone and proparathyroid hormone in extracts of tissues and media were measured by polyacrylamide gel electrophoresis and by radioimmunoassay, respectively. All tissues studied (six adenomas, two specimens of chief-cell hyperplasia, one carcinoma, and normal bovine and human glands) responded to changes in calcium concentrations; decreasing concentrations of calcium stimulated release and decreased tissue storage of hormone. Six of the abnormal tissues required greater than normal concentrations of calcium (1.8-2.4 mM for 50% of effect) to elicit secretory responses comparable with those of normal glands (1.4 mM). Maximum effects of calcium on release of hormone varied from 2- to 10-fold among different tissues. Release of some hormone persisted even in concentrations of calcium as high as 5.0 mM. Relative amounts of hormone released from and retained in the tissues varied greatly among the tissues, as did the absolute amounts of hormone produced; newly synthesized, labeled hormone ranged between 0.6 and 12% of total labeled protein, and immunoreactive hormone ranged between 0.015 and 0.9% of total tissue protein. Effects of calcium on hormone biosynthesis, as determined by analyses of amounts of proparathyroid hormone in the tissues, were variable among tissues and in many cases were negligible. These results indicate that neoplastic and hyperplastic parathyroid tissues retain secretory responsiveness to changes in extracellular concentrations of calcium. Responses, however, are highly variable among different tissues, and in many instances are abnormal, inasmuch as

  12. Parathyroid function following total thyroidectomy using energy devices.

    PubMed

    Ciftci, Fatih; Sakalli, Erdal; Abdurrahman, Ibrahim; Guler, Burak

    2016-07-01

    LigaSure precise (LP) and harmonic scalpel (HS) are two energy-based devices used in thyroidectomy surgery. We aimed to compare the effect of these two devices in patients who had undergone total thyroidectomy, by highlighting the post-operative parathyroid function. A total of 201 consecutive patients for whom total thyroidectomy had been planned were prospectively classified into two groups. There were 104 patients in LP group and 97 patients in HS group. Hypoparathyroidism was followed up by serially measuring the levels of intact parathyroid hormone (iPTH) and serum calcium. The early iPTH level was 29 (8-50) pg/mL in group LP, and 17 (4-43) pg/mL in group HS. The early iPTH level was significantly lower in the HS group (p < 0.001). However, these levels were within the reference interval in both groups. The early iPTH level was lower than 20 pg/mL in 23 (23.1 %) patients in HS group, and 15 (13.7 %) patients in LP group (p < 0.001). Also, the late iPTH levels were not statistically significance between two groups. The early and late serum calcium levels were not statistically significant between groups. However, the amount of calcium replacement was higher in the HS group than the LP group and the duration of treatment was longer in the HS group than the LP group (p < 0.05). In conclusion, although parathyroid hormone levels impaired in the HS group more than LP group in the early period, these levels were in the normal limits in both groups. These levels were not significant between groups in the long time period. PMID:26141753

  13. Challenging neck mass: non-functional giant parathyroid adenoma.

    PubMed

    Mossinelli, Chiara; Saibene, Alberto Maria; De Pasquale, Loredana; Maccari, Alberto

    2016-01-01

    A 46-year-old man was referred to our ear, nose and throat department after the accidental discovery of a large retrotracheal mass. In order to obtain the diagnosis and to plan treatment he underwent a full battery of tests (CT, MRI, blood tests, hormonal assays, ultrasounds, thyroid scintigraphy, urine tests and fine-needle aspiration of the mass), but none of these was able to define the true nature of such cervical mass. Only after surgical excision and histological evaluation, it was diagnosed as an exceptional case of giant non-functional parathyroid adenoma. PMID:27535730

  14. The Significance of Ultrasound in Determining Whether SHPT Patients Are Sensitive to Calcitriol Treatment

    PubMed Central

    Liang, Xing-xin; Li, Fan; Gao, Feng; Li, Chun-xiao; Qiao, Xiao-hui; Zhang, Jia-jie

    2016-01-01

    This study was to explore the significance of ultrasound in determining whether the patients with secondary hyperparathyroidism (SHPT) are sensitive to calcitriol treatment. According to the decrease value of parathyroid hormone (PTH), 42 SHPT patients were divided into two groups: drug susceptible group and drug insusceptible group. These 42 SHPT patients' ultrasound images were retrospectively analyzed. The morphology, size, number, blood flow, elastic modulus, and perfusion of the parathyroid glands were correlated with drug therapeutic outcome (oral calcitriol). Most SHPT patients with drug susceptible showed volume <438.50 mm3 and number ≤2, with 0-1 structural and vascular patterns, associated with Relative Maximum Intensity (RIMAX) <1.59 and elastic modulus <18.8 kPa, whereas most SHPT patients with drug insusceptible showed volume ≥438.50 mm3 and number ≥3, with 2-3 structural and vascular patterns, associated with Relative Maximum Intensity (RIMAX) ≥1.59 and elastic modulus ≥18.8 kPa. Therefore, ultrasonography in SHPT allows an accurate definition of the morphology, size, number, blood flow, elastic modulus, and perfusion of the parathyroid glands and is useful in determining whether SHPT patients are sensitive to calcitriol treatment. PMID:27034943

  15. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells.

    PubMed

    Krajisnik, Tijana; Björklund, Peyman; Marsell, Richard; Ljunggren, Osten; Akerström, Göran; Jonsson, Kenneth B; Westin, Gunnar; Larsson, Tobias E

    2007-10-01

    Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D(3). Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities in Pi and vitamin D metabolism. The objective of the current study was therefore to elucidate possible direct effects of FGF23 on bovine parathyroid cells in vitro. Treatment of parathyroid cells with a stabilized form of recombinant FGF23 (FGF23(R176Q)) induced a rise in early response gene-1 mRNA transcripts, a marker of FGF23 signaling. FGF23(R176Q) potently and dose-dependently decreased the PTH mRNA level within 12 h. In agreement, FGF23(R176Q) also decreased PTH secretion into conditioned media. In contrast, FGF23(R176Q) dose-dependently increased 1alpha-hydroxylase expression within 3 h. FGF23 (R176Q) did not affect cell viability nor induce apoptosis, whereas a small but significant increase in cell proliferation was found. We conclude that FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro. Our data suggest that FGF23 may be a physiologically relevant regulator of PTH. This defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism. PMID:17911404

  16. Observations on the effect of parathyroid hormone on environmental blood lead concentrations in humans

    SciTech Connect

    Osterloh, J.D. )

    1991-02-01

    The effect of parathyroid hormone (PTH) on blood lead (Pb) concentrations was observed preliminarily in three different situations. Of 342 healthy bus drivers with no unusual exposure to Pb, 25 drivers with the highest and 25 with the lowest blood Pb were compared for serum PTH concentrations. There was no association between blood Pb and serum PTH concentrations. Eight women with postmenopausal osteoporosis enrolled in an experimental protocol to increase bone mass received daily PTH (1-34 fragment) for 1 week, calcitonin for the next 2 weeks, and oral calcium for the subsequent 10 weeks. This cycle was repeated four times during the year. Initial blood Pb concentrations averaged 6.0 micrograms/dl (range 2.1-8.9). Mean blood Pb concentrations decreased by 1.7 micrograms/dl over 1 year of therapy. The confidence interval for this change excluded zero, the mean change was significantly different from the mean change for comparative population (P less than 0.050), and paired changes were statistically significant (P = 0.045). Lastly, a single subject with hyperparathyroid disease and no unusual exposures to lead demonstrated stabilized blood Pb concentrations that were 50% lower after removal of his hyperplastic parathyroid glands. These observations suggest that the effect of PTH on increasing bone turnover and releasing Pb into blood is not easily detected at low physiologic amounts of PTH, but that with pathologic increases of PTH in hyperparathyroid disease, elevation of blood Pb from bone or increased gastrointestinal absorption may be possible. Likewise, either bone building therapies (PTH + calcitonin + calcium) may move Pb from blood into bone or supplemental calcium may decrease Pb gastrointestinal absorption, thereby explaining the observed lower blood Pb concentrations.

  17. Multiple brown tumors in parathyroid carcinoma mimicking metastatic bone disease.

    PubMed

    Pai, M; Park, C H; Kim, B S; Chung, Y S; Park, H B

    1997-10-01

    An unusual case of multiple brown tumors due to parathyroid carcinoma is reported. The patient presented with lower leg pain. Plain radiographs demonstrated multiple lytic lesions of the lower legs and a Tc-99m MDP bone scan depicted multiple areas of increased uptake suggesting skeletal metastases. Tc-99m sestamibi tumor scintigraphy showed multiple sites of tumor uptake in bones and a large area of increased uptake with a cystic component in the right lower pole of the thyroid gland. An open biopsy from the right tibial lesion revealed a brown tumor. A large parathyroid carcinoma with a necrotic cyst was removed. After parathyroidectomy and right thyroid lobectomy, the patient became free of bone pain and serum PTH levels normalized. A 9-month follow-up Tc-99m MDP bone scan demonstrated less intense uptake in the pelvis, tibia, and fibulae. Nine-month follow-up tumor imaging with Tc-99m MIBI revealed disappearance of the preoperative uptake of multiple brown tumor. PMID:9343725

  18. An unusual mediastinal parathyroid carcinoma coproducing PTH and PTHrP: A case report

    PubMed Central

    CAO, CHUANGJIE; DOU, CHENGYUN; CHEN, FUQIN; WANG, YAN; ZHANG, XIAOLI; LAI, HONG

    2016-01-01

    Parathyroid carcinoma (PTCA) is a rare disease, and ectopic PTCA is particularly rare. Parathyroid hormone-related protein (PTHrP) expression in PTCA has not been previously described in the relevant literature to the best of our knowledge. The present study reports a unique case with a mediastinal parathyroid carcinoma producing parathyroid hormone (PTH) and PTHrP. A 53-year-old man presented with hyperparathyroidism symptoms, including fatigue, chest pain, dizziness, muscular soreness, polyuria, night sweats and renal stones. However, neck ultrasound revealed no significantly abnormal thyroid or parathyroid nodules. Tc99m methoxyisobutylisonitrile (Tc99m-MIBI) scintigraphy scanning indicated an ectopic mediastinal parathyroid adenoma. Histopathological examination revealed PTCA, and the tumor tissue was coproducing PTH and PTHrP. The patient underwent successful surgical operation. Serum calcium and PTH levels remained within normal ranges, and there was no tumor recurrence observed at a 3-year follow-up appointment. Although rare, ectopic parathyroid glands may lead to malignant disease. Clinical symptoms, biochemical tests, ultrasound and Tc99m-MIBI scintigraphy scanning may assist with the diagnosis of this disease. Hypersecretion of PTHrP and PTH contributed collaboratively to the pathogenesis of hypercalcemia due to PTCA. Complete surgical resection with microscopically negative margins is the recommended treatment for PTCA and offers the best chance of a cure. PMID:27313750

  19. Influence of blanketing and season on vitamin D and parathyroid hormone, calcium, phosphorus, and magnesium concentrations in horses in New Zealand.

    PubMed

    Azarpeykan, S; Dittmer, K E; Gee, E K; Marshall, J C; Wallace, J; Elder, P; Acke, E; Thompson, K G

    2016-07-01

    The aims of the study were to determine the effect of season and blanketing on vitamin D synthesis in horses and examine the interaction between vitamin D and other analytes involved in calcium homeostasis. Twenty-one healthy horses at pasture were included; 5 were covered with standard horse blankets including neck rugs. Blood samples were collected for 13 mo and analyzed for 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D (1,25[OH]2D), ionized calcium (iCa), total calcium (tCa), phosphorus (P), total magnesium (tMg), and parathyroid hormone (PTH). Grass and hay samples were collected and analyzed for vitamin D, calcium, phosphorus, and magnesium. Climate data were also collected. The serum concentration of 25OHD3 in horses was either undetectable or below the detection limit of the assay, and the main form of 25OHD was 25OHD2. No differences in serum 25OHD2, 1,25(OH)2D, iCa, tCa, P, tMg, and PTH (P ≥ 0.05) concentrations were seen between the 2 groups. Associations were seen between iCa and PTH (P < 0.05), iCa and tMg (P < 0.05), and dietary vitamin D and 25OHD2 (P < 0.05). A strong seasonal trend was seen in serum 25OHD2 (P < 0.0001), which was higher during spring and summer when the amount of sunshine and UV radiation was higher. Parathyroid hormone and 1,25(OH)2D showed opposing trends with PTH higher in winter whereas 1,25(OH)2D was higher in summer. The results suggest that dietary vitamin D may be necessary for horses to fulfill their vitamin D requirements; however, further research is required to determine the contribution of vitamin D3 synthesis in the skin to the vitamin D status of the horse. PMID:27131337

  20. Endogenous parathyroid hormone-related protein compensates for the absence of parathyroid hormone in promoting bone accrual in vivo in a model of bone marrow ablation.

    PubMed

    Zhu, Qi; Zhou, Xichao; Zhu, Min; Wang, Qian; Goltzman, David; Karaplis, Andrew; Miao, Dengshun

    2013-09-01

    To assess the effect of hypoparathyroidism on osteogenesis and bone turnover in vivo, bone marrow ablation (BMXs) were performed in tibias of 8-week-old wild-type and parathyroid hormone-null (PTH(-/-)) mice and newly formed bone tissue was analyzed from 5 days to 3 weeks after BMX. At 1 week after BMX, trabecular bone volume, osteoblast numbers, alkaline phosphatase-positive areas, type I collagen-positive areas, PTH receptor-positive areas, calcium sensing receptor-positive areas, and expression of bone formation-related genes were all decreased significantly in the diaphyseal regions of bones of PTH(-/-) mice compared to wild-type mice. In contrast, by 2 weeks after BMX, all parameters related to osteoblastic bone accrual were increased significantly in PTH(-/-) mice. At 5 days after BMX, active tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts had appeared in wild-type mice but were undetectable in PTH(-/-) mice, Both the ratio of mRNA levels of receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) and TRAP-positive osteoclast surface were still reduced in PTH(-/-) mice at 1 week but were increased by 2 weeks after BMX. The expression levels of parathyroid hormone-related protein (PTHrP) at both mRNA and protein levels were upregulated significantly at 1 week and more dramatically at 2 weeks after BMX in PTH(-/-) mice. To determine whether the increased newly formed bones in PTH(-/-) mice at 2 weeks after BMX resulted from the compensatory action of PTHrP, PTH(-/-) PTHrP(+/-) mice were generated and newly formed bone tissue was compared in these mice with PTH(-/-) and wild-type mice at 2 weeks after BMX. All parameters related to osteoblastic bone formation and osteoclastic bone resorption were reduced significantly in PTH(-/-) PTHrP(+/-) mice compared to PTH(-/-) mice. These results demonstrate that PTH deficiency itself impairs osteogenesis, osteoclastogenesis, and osteoclastic bone resorption, whereas subsequent upregulation of PTHr

  1. Adipose-derived stem cells: A novel source of parathyroid cells for treatment of hypoparathyroidism.

    PubMed

    Zhao, Yue; Luo, Bin

    2016-08-01

    Hypoparathyroidism is characterized by decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH), which can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany, and several other symptoms. Severe hypocalcemia is a life-threatening condition. At present, both medical and surgical treatments are offered to improve the blood calcium, but they are not a cure. Adipose-derived stem cells (ADSCs), derived from the adipose tissue, are confirmed to be multipotent with adipogenic, chondrogenic, neurogenic, myogenic and osteogenic capabilities. Our hypothesis is that human ADSCs in culture can be differentiated into parathyroid cells, and used to reconstitute function. PMID:27372875

  2. Heterogeneity of Parathyroid Hormone. CLINICAL AND PHYSIOLOGIC IMPLICATIONS

    PubMed Central

    Silverman, Robert; Yalow, Rosalyn S.

    1973-01-01

    When immunoreactive human parathyroid hormone (hPTH), extracted by three different solvents (20% acetone in 1% acetic acid, 8 M urea, or normal saline) from parathyroid glandular tissue was subjected to Sephadex G-100 gel filtration and immunoassay using two different antisera (273 and C-329), four distinct fractions were observed. The first (I), a void volume peak, was detected by both antisera with similar immunoreactivity, as was a second (II), which had the elution and sedimentation properties of highly purified bovine parathyroid hormone (bPTH); a third (III) eluted between [125I]growth hormone and [125I]insulin, sedimented with the velocity of a molecule of approximately 6,000 mol wt, and was detected primarily by antiserum 273; a final fraction (IV), detected primarily by C-329, eluted just prior to [125I]insulin. The elution profiles of the acetone-acetic acid and 8 M urea extracts were similar and contained fraction II as their major component. In saline extracts, however, fraction III predominated. Three fractions, having gel filtration and immunologic characteristics similar to fractions II, III, and IV, respectively, of saline glandular extracts, were detected in the plasma of patients with both primary (adenomatous or carcinomatous) and secondary hyperparathyroidism. The predominant component in every plasma was the intermediate fraction that, like III, was detected primarily by antiserum 273, while the least abundant form was consistently the final fraction, detected primarily by antiserum C-329. The first fraction, like II, was detected with about equal potency by both antisera and had an elution volume on Sephadex corresponding to that of intact bPTH. It bore a reciprocal relationship to serum calcium and disappeared from the plasma of a uremic patient during calcium infusion or following parathyroidectomy with a half-time of no more than 20 min. This component therefore probably represents biologically active hormone. The intermediate and final

  3. Use of pre-operative Tc99m-Sestamibi scintigraphy and intraoperative parathyroid hormone monitoring to eliminate neck exploration in mediastinal parathyroid adenocarcinoma.

    PubMed

    Damadi, Amir; Harkema, James; Kareti, Rao; Saxe, Andrew

    2007-01-01

    A 66-year-old white woman was found to have an elevated serum calcium and parathyroid hormone (PTH) on routine health evaluation. Physical examination was unremarkable as was ultrasonography of the neck. A sestamibi parathyroid scan revealed abnormal uptake in the anterior mediastinum. Computed tomography of the chest demonstrated an anterior mediastinal mass compatible with a parathyroid adenoma but no neck masses. The patient underwent mediastinoscopy that was converted to a median sternotomy to fully access the mass. The mass was completely resected with surrounding thymus gland. Frozen section confirmed that excised tissue was parathyroid gland in origin. An intraoperative PTH obtained 20 minutes after specimen removal showed a decrease of more than 50% from preoperative levels. The strategy for initial surgery for hyperparathyroidism when a sestamibi scan is "positive" in the mediastinum (only) is a point of some controversy. Traditional recommendations have been to "clear the neck" of abnormal parathyroid tissue before undertaking a more morbid sternotomy. Mediastinoscopy was attempted to remove the mediastinal lesion and to avoid a sternotomy. Preoperative Tc99m sestamibi scintigraphy, frozen section histology, and intraoperative PTH monitoring permitted the authors to conclude that neck exploration was unnecessary. PMID:17462212

  4. Radioisotopic evaluation of the thyroid and the parathyroids.

    PubMed

    Price, D C

    1993-09-01

    Since the inception of the discipline of nuclear medicine, thyroid evaluation and therapy with radioactive isotopes have remained an important and constant component of thyroidology. Parathyroid scintigraphy with 201Tl/99mTc subtraction has been a more recent and also very useful addition in the assessment of hyperparathyroidism, particularly at reoperation. The radioactive iodine uptake test gives important metabolic information on thyroid function in such diverse disease states as hyperthyroidism, hypothyroidism, the thyroiditides, and thyroid carcinoma. Thyroid scintigraphy is also a key contributor to the assessment of patients with hyperthyroidism or with single versus multiple thyroid nodules, those with a history of head and neck irradiation during childhood, and those requiring diagnostic follow-up studies with 131I after total thyroidectomy for differentiated thyroid carcinoma. Each of these topics is reviewed and expanded on in this article, with a diversity of illustrative scans provided to complement the discussion. PMID:8362060

  5. Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone

    NASA Technical Reports Server (NTRS)

    Hillsley, M. V.; Frangos, J. A.

    1996-01-01

    It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.

  6. Parathyroid adenoma in a young male with multiple fractures and varied clinical features.

    PubMed

    Bhanu Murthy, R; Srihari, V; Lakshmi Narayana, M

    2014-01-01

    Primary hyperparathyroidism is due to parathyroid adenoma (80-85%), hyperplasia (10-15%), carcinoma (2-3%) of cases. The most common presentation is asymptomatic hypercalcemia. Multiple pathological fractures, nephrocalcinosis as a presenting feature of primary hyperparathyroidism due to parathyroid adenoma is extremely rare at the age of 19 years. A case of parathyroid adenoma with multiple fractures of left femur, renal calculi, nephrocalcinosis, weight loss, constipation, dyspepsia abdominal pain was presented. The case was investigated completely with biochemical investigations, X-ray of forearm bones and femur, ultrasonography of neck and abdomen, CT scan of neck and abdomen, MRI scan, Scintigraphy of the neck. Right inferior parathyroid adenoma was diagnosed and confirmed by histopathological examination after excision. The post operative serum calcium levels became normal. PMID:24605315

  7. [Usefulness of power Doppler ultrasonography for the diagnosis of autoinfarction of parathyroid gland in secondary hyperparathyroidism].

    PubMed

    Tanaka, Motoko; Ito, Kazuko; Matsushita, Kazunori; Matsushita, Kazutaka; Tominaga, Yoshihiro; Matsuoka, Susumu; Ueki, Tsuneo; Goto, Norihiko; Sato, Tetsuhiko; Katayama, Akio; Haba, Toshihito; Uchida, Kazuharu

    2005-09-01

    Spontaneous remission due to parathyroid infarction of secondary hyperparathyroidism is rare compared with that of primary hyperparathyroidism, probably because several glands are enlarged in secondary hyperparathyroidism. Lately, neck ultrasound examination has become a more beneficial and specific method for the diagnosis of enlarged parathyroid glands in contrast to classic diagnostic techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy. However, the diagnosis of parathyroid infarction reported in previous studies was often based on CT, MRI and scintigraphy findings and there are few studies that reported such diagnosis by urgent power Doppler ultrasonography of the neck. Here we present a hemodialysis patient with autoinfarction of the left parathyroid gland diagnosed by urgent power Doppler ultrasonography of the neck. PMID:16272629

  8. FDG-anorectic parathyroid carcinoma with FDG-avid bone metastasis on PET/CT images.

    PubMed

    Li, Mei; Lu, Hankui; Gao, Yunchao

    2013-11-01

    A 53-year-old man complained of aggravated left hip pain of more than 2 months. Whole-body (18)F-FDG PET/CT revealed only 1 hypermetabolic lesion in the left ilium. Histopathologic examination of the lesion suggested metastatic disease. Blood tests documented mildly elevated blood calcium and parathyroid hormone. Subsequent neck ultrasonography, contrast-enhanced CT, and dual-phase scintigraphy with (99m)Tc-MIBI showed a right parathyroid tumor, which was confirmed to be a parathyroid carcinoma postoperatively. We report a case of parathyroid carcinoma rarely encountered with a FDG-negative primary but a FDG-positive metastasis on PET/CT images. PMID:24089062

  9. Contrast Agent Ultrasonography before and after HIFU Treatment of Parathyroid Glands

    NASA Astrophysics Data System (ADS)

    Kovatcheva, Roussanka; Arnaud, Françoise; Lacoste, François

    2010-03-01

    OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B-Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

  10. Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism.

    PubMed Central

    Fraker, D L; Travis, W D; Merendino, J J; Zimering, M B; Streeten, E A; Weinstein, L S; Marx, S J; Spiegel, A M; Aurbach, G D; Doppman, J L

    1991-01-01

    Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity. PMID:1985539

  11. Effects of maintenance lithium treatment on serum parathyroid hormone and calcium levels: a retrospective longitudinal naturalistic study

    PubMed Central

    Albert, Umberto; De Cori, David; Aguglia, Andrea; Barbaro, Francesca; Lanfranco, Fabio; Bogetto, Filippo; Maina, Giuseppe

    2015-01-01

    Objective The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. Methods A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010–2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. Results A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. Conclusion Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added. PMID:26229473

  12. Determining the Pathogenicity of Genetic Variants Associated with Cardiac Channelopathies

    PubMed Central

    Campuzano, Oscar; Allegue, Catarina; Fernandez, Anna; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    Advancements in genetic screening have generated massive amounts of data on genetic variation; however, a lack of clear pathogenic stratification has left most variants classified as being of unknown significance. This is a critical limitation for translating genetic data into clinical practice. Genetic screening is currently recommended in the guidelines for diagnosis and treatment of cardiac channelopathies, which are major contributors to sudden cardiac death in young people. We propose to characterize the pathogenicity of genetic variants associated with cardiac channelopathies using a stratified scoring system. The development of this system was considered by using all of the tools currently available to define pathogenicity. The use of this scoring system could help clinicians to understand the limitations of genetic associations with a disease, and help them better define the role that genetics can have in their clinical routine. PMID:25608792

  13. Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies.

    PubMed

    Isobe, Kaori; Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2016-07-01

    The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID:27559247

  14. Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies

    PubMed Central

    Isobe, Kaori; Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2016-01-01

    The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID:27559247

  15. Effects of a 2X gravity environment on the ultrastructure of the gerbil parathyroid gland

    NASA Technical Reports Server (NTRS)

    Sannes, P. L.; Hayes, T. G.

    1975-01-01

    A number of studies concerning the effects of hypergravity on bone have shown increases in bone mass or bone dimensions. Correlative studies, which could provide clues to the mechanism for such a response, have been lacking. The purpose of the present study was to evaluate the ultrastructure of parathyroid glands of Mongolian gerbils exposed to a continuous 2 X gravity force for 60 d. It was found that the experimental animals had parathyroid glands which had a greater percentage of chief cells in the active stage of their secretory cycle when compared with control animals. This result was interpreted to indicate an increase in parathyroid gland secretory activity and, hence, an increase in parathyroid hormone release. It was suggested that increased parathyroid secretory activity was necessary to maintain serum calcium levels of hypergravity animals within normal limits. Cellular forms resembling water clear cells and highly compact, degenerating cells were described in experimental animals but not in controls. Areas suggestive of cellular dissolution and disorganization were also reported in experimental parathyroids.

  16. Histopathological Changes of the Thyroid and Parathyroid Glands in HIV-Infected Patients

    PubMed Central

    Shakir, K. M. Mohamed; Shokrani, Babak; Madduri, Sujay; Mody, Vinod

    2014-01-01

    Objective. To study histopathology of the thyroid and parathyroid glands in HIV-infected African Americans in the United States. Methods. A retrospective review of 102 autopsy cases done by the Department of Pathology at Howard University Hospital from 1980 through 2007 was conducted. The histopathological findings of the thyroid and parathyroid glands were reviewed, both macroscopically and microscopically. A control group of autopsy patients with chronic non-HIV diseases was examined. Results. There were 71 males (70%) and 31 females (30%) with an average age of 38 years (range: 20–71 y). Thirteen patients with abnormal thyroid findings were identified. Interstitial fibrosis was the most common histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious disease affecting the thyroid gland was limited to 2.9% and consisted of mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid hyperplasia was the most common histological change noted in the parathyroid glands. Comparing the histological findings of cases and controls, we found a similar involvement of the thyroid, with a greater prevalence of parathyroid hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities are uncommon findings in the HIV-infected African American population. PMID:24587936

  17. Vascular effects of parathyroid hormone and parathyroid hormone-related protein in the split hydronephrotic rat kidney.

    PubMed Central

    Endlich, K; Massfelder, T; Helwig, J J; Steinhausen, M

    1995-01-01

    1. The effects of locally applied parathyroid hormone-related protein (PTHRP), a putative autocrine/paracrine hormone, on vascular diameters and glomerular blood flow (GBF) in the split hydronephrotic rat kidney were studied. As PTHRP interacts with parathyroid hormone (PTH) receptors in all tissues tested so far, the effects of PTHRP were compared with those of PTH. 2. Preglomerular vessels dilated in a concentration- and time-dependent manner that was almost identical for PTH and PTHRP. A significant preglomerular vasodilation (5-17%) occurred at a threshold concentration of 10(-10) mol l-1 PTH or PTHRP, which raised GBF by 20 +/- 2 and 31 +/- 4%, respectively (means +/- S.E.M., n = 6). PTH or PTHRP (10(-7) mol l-1) increased preglomerular diameters (11-36%) and GBF (60 +/- 10 and 70 +/- 8%, respectively) to near maximum. The most prominent dilatation was located at the interlobular artery and at the proximal afferent arteriole. 3. Efferent arterioles were not affected by either PTH or PTHRP. 4. Estimated concentrations of half-maximal response (EC50) for preglomerular vasodilatation and GBF increase were in the nanomolar to subnanomolar range. 5. After inhibition of angiotensin I-converting enzyme by 2 x 10(-6) mol kg-1 quinapril I.V. (n = 6), 10(-8) mol l-1 PTHRP dilated preglomerular vessels and efferent arterioles (9 +/- 1% proximal and 6 +/- 1% distal). 6. We conclude that the renal vasculature of the hydronephrotic kidney is highly sensitive to vasodilatation by PTH and PTHRP, which, in addition, may constrict efferent arterioles by stimulating renin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7650615

  18. Parathyroid hormone and arterial dysfunction in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Bosworth, Cortney; Sachs, Michael C.; Duprez, Daniel; Hoofnagle, Andrew N.; Ix, Joachim H.; Jacobs, David R.; Peralta, Carmen A.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.

    2013-01-01

    Objective High circulating concentrations of parathyroid hormone (PTH) have been associated with increased risks of hypertension, left ventricular hypertrophy, congestive heart failure, and cardiovascular mortality. Impaired arterial function is a potential mechanism for these associations. We tested whether serum PTH concentration is associated with measures of arterial function. Design Cross-sectional study. Participants 6,545 persons without clinical cardiovascular disease participating in the community-based Multi-Ethnic Study of Atherosclerosis. Measurements Brachial artery flow-mediated dilation as well as aortic pulse pressure and arterial pulse parameters derived from Windkessel modeling of the radial pressure waveform. Results Higher serum PTH concentration was associated with lower brachial artery flow-mediated dilation (mean difference −0.09% per 10 pg/mL PTH), higher aortic pulse pressure (0.53 mmHg per 10 pg/mL), and reduced Windkessel capacitive index C1 (large artery elasticity, −0.12 ml/mmHg X 10 per 10 pg/mL), adjusting for potential confounding variables (all p-values ≤ 0.001). These relationships were independent of serum calcium concentration, serum 25-hydroxyvitamin D concentration, and estimated glomerular filtration rate and were consistent across relevant participant subgroups. Associations of PTH with aortic pulse pressure and capacitive index C1 were attenuated after adjustment for blood pressure. Serum PTH concentration was not associated with the oscillatory index C2 (small artery elasticity). Conclusions Higher serum PTH concentration was associated with impaired endothelial function, increased aortic pulse pressure, and decreased capacitive index C1 in a large, diverse, community-based population. These relationships may help explain previously observed associations of elevated PTH with cardiovascular disease. PMID:23402353

  19. High Parathyroid Hormone Level and Osteoporosis Predict Progression of Coronary Artery Calcification in Patients on Dialysis.

    PubMed

    Malluche, Hartmut H; Blomquist, Gustav; Monier-Faugere, Marie-Claude; Cantor, Thomas L; Davenport, Daniel L

    2015-10-01

    Coronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bone markers. A total of 213 patients received baseline measurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores>400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD-associated CAC prevalence and progression. PMID:25838468

  20. A rare complication of transitional cell carcinoma of the renal pelvis: parathyroid hormone-related peptide-induced hypercalcaemia.

    PubMed

    O Sullivan, Eoin; Plant, William

    2014-01-01

    We describe a rare occurrence of parathyroid hormone-related peptide (PTHrp) associated hypercalcaemia with a recurrence of transitional cell carcinoma of the renal pelvis. Our patient presented with serum calcium of 3.9 mmol/L, PTH of 5 ng/L and a PTHrp of 9.8 pmol/L (<2 pmol/L). He had no evidence of metastatic disease. His hypercalcaemia responded to bisphosphonate therapy. He chose to be treated conservatively and died 5 weeks after presentation. This is the seventh such case described in the literature. PTHrp-induced hypercalcaemia is associated with a grave prognosis, with a mean survival of 65 days from presentation. PMID:24951595

  1. Subunit association as the stabilizing determinant for archaeal methionine adenosyltransferases.

    PubMed

    Garrido, Francisco; Alfonso, Carlos; Taylor, John C; Markham, George D; Pajares, María A

    2009-07-01

    Archaea contain a class of methionine adenosyltransferases (MATs) that exhibit substantially higher stability than their mesophilic counterparts. Their sequences are highly divergent, but preserve the essential active site motifs of the family. We have investigated the origin of this increased stability using chemical denaturation experiments on Methanococcus jannaschii MAT (Mj-MAT) and mutants containing single tryptophans in place of tyrosine residues. The results from fluorescence, circular dichroism, hydrodynamic, and enzyme activity measurements showed that the higher stability of Mj-MAT derives largely from a tighter association of its subunits in the dimer. Local fluorescence changes, interpreted using secondary structure predictions, further identify the least stable structural elements as the C-terminal ends of beta-strands E2 and E6, and the N-terminus of E3. Dimer dissociation however requires a wider perturbation of the molecule. Additional analysis was initially hindered by the lack of crystal structures for archaeal MATs, a limitation that we overcame by construction of a 3D-homology model of Mj-MAT. This model predicts preservation of the chain topology and three-domain organization typical of this family, locates the least stable structural elements at the flat contact surface between monomers, and shows that alterations in all three domains are required for dimer dissociation. PMID:19348969

  2. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D3 [Δ25(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  3. Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density

    PubMed Central

    Kota, Sunil; Jammula, Sruti; Kota, Siva; Meher, Lalit; Modi, Kirtikumar

    2013-01-01

    Background: Bone mineral densiy (BMD) is known to be affected by serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD) in a cohort of Indian patients. Materials and Methods: Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate regression models were used to investigate the relationships between serum 25(OH) D, iPTH and BMD. Results: Total of 102 patients (male:female = 38:64) with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH) D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml (Normal = 30-74 ng/ml), confirming vitamin D deficiency. There was no association between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI) and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH) D was negatively associated with iPTH (P = 0.041). Conclusion: Among our cohort of patients with low BMD, no direct relationship between serum 25(OH) D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of

  4. Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.

    PubMed

    Deo, Rajat; Katz, Ronit; Shlipak, Michael G; Sotoodehnia, Nona; Psaty, Bruce M; Sarnak, Mark J; Fried, Linda F; Chonchol, Michel; de Boer, Ian H; Enquobahrie, Daniel; Siscovick, David; Kestenbaum, Bryan

    2011-12-01

    Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. PMID:22068871

  5. Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Ryder, K. D.; Duncan, R. L.

    2000-01-01

    Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

  6. Effect of parathyroid hormone on transport by toad and turtle bladder

    SciTech Connect

    Sabatini, S.; Kurtzman, N.A.

    1987-01-01

    The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H/sub 2/O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H/sub 2/O and Na transport and H..mu.. secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H/sub 2/O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P < 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H/sup +/ secretion in turtle bladders. Both PTH and A23187 increased /sup 45/Ca uptake in toad bladder epithelial cells; only A23187 increased /sup 45/Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different.

  7. Studies on the use of cultured cells in a bioassay for parathyroid hormone.

    PubMed

    Armston, A E; Wood, P J

    1994-11-01

    Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and hypoparathyroidism. The move to two-site immunometric assays that detect the whole molecule has improved the discrimination of these conditions but these assays may be too restrictive because some PTH fragments that are biologically active may not be detected. In addition, PTH-like peptide of malignancy, an important cause of malignancy-associated hypercalcaemia, is not detected by the two-site assays. Experiments were performed to set up a simple, robust and inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP or an eluted stain assay as the end point. Of the 12 cell lines tested, an opossum kidney (WOK) cell line showed the most promise. Despite optimization of the procedure to include pre-treatment with dexamethasone, insulin and PTH, followed by incubation in the presence of 5'-guanylimidodiphosphate, isobutyl-1-methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for use in a cultured cell bioassay for PTH in human serum. In addition, the cells were less sensitive to PTH-like peptide precluding their use for an assay for this molecule. PMID:7829991

  8. [Role of parathyroid hormone in Klotho-FGF23 system].

    PubMed

    Kimura, Takaaki; Shiizaki, Kazuhiro; Kuro-O, Makoto

    2016-06-01

    Klotho was originally identified as an anti-aging gene that accelerated aging when disrupted and extended life span when overexpressed in mice. The Klotho gene encodes a single-pass transmembrane protein and is expressed in the kidney and parathyroid gland. Klotho protein functions as an obligate subunit of the receptor for fibroblast growth factor 23(FGF23). FGF23 is a hormone secreted from osteocytes and osteoblasts and acts on renal tubular cells to promote phosphate excretion into the urine and suppress synthesis of active form of vitamin D(1,25-dihydroxyvitamin D3;1,25(OH)2D3). Decreased Klotho expression due to the kidney damage including CKD might increase the circulating level of FGF23 and trigger disturbed mineral-bone metabolism, leading to CKD-MBD. Characteristic features of CKD-MBD including hyperphosphatemia, hypocalcemia, and decreased serum 1,25(OH)2D3 can be explained by(mal)adaptation of the Klotho-FGF23 system, which also contributes to the pathophysiology of secondary hyperparathyroidism(SHPT). In addition to its function as a receptor for FGF23, the extracellular domain of Klotho is secreted by ectodomain shedding and functions as a humoral factor that regulates multiple ion channels and transporters. Thus, Klotho has emerged as a key regulator of mineral metabolism in health and disease. PMID:27230841

  9. Parathyroid hormone accelerates decompensation following left ventricular hypertrophy

    PubMed Central

    Cha, Hyeseon; Jeong, Hyeon Joo; Jang, Seung Pil; Kim, Joo Yeon; Yang, Dong Kwon; Oh, Jae Gyun

    2010-01-01

    Parathyroid hormone (PTH) treatment was previously shown to improve cardiac function after myocardial infarction by enhancing neovascularization and cell survival. In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left ventricular internal dimension. Increases in the heart weight to body weight ratio and lung weight to body weight ratio following TAB were significantly exacerbated in PTH-treated mice compared to saline-treated mice. Molecular markers for heart failure, fibrosis, and angiogenesis were also altered in accordance with more severe heart failure in the PTH-treated mice compared to the saline-treated mice following TAB. In addition, the PTH-treated hearts were manifested with increased fibrosis accompanied by an enhanced SMAD2 phosphorylation. These data suggest that the PTH treatment may accelerate the process of decompensation of LV, leading to heart failure. PMID:19887893

  10. Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies.

    PubMed

    Esbrit, Pedro; Herrera, Sabina; Portal-Núñez, Sergio; Nogués, Xavier; Díez-Pérez, Adolfo

    2016-04-01

    The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies. PMID:26259869

  11. Pulsatile Release of Parathyroid Hormone from an Implantable Delivery System

    PubMed Central

    Liu, Xiaohua; Pettway, Glenda J.; McCauley, Laurie K.; Ma, Peter X.

    2007-01-01

    Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. PMID:17576005

  12. Parathyroid hormone-related protein is required for tooth eruption

    PubMed Central

    Philbrick, William M.; Dreyer, Barbara E.; Nakchbandi, Inaam A.; Karaplis, Andrew C.

    1998-01-01

    Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes of transgenic mice produces a delay in chondrocyte maturation and endochondral ossification. Replacement of PTHrP expression in the chondrocytes of PTHrP-knockout mice using a procollagen II-driven transgene results in the correction of the lethal skeletal abnormalities and generates animals that are effectively PTHrP-null in all sites other than cartilage. These rescued PTHrP-knockout mice survive to at least 6 months of age but are small in stature and display a number of developmental defects, including cranial chondrodystrophy and a failure of tooth eruption. Teeth appear to develop normally but become trapped by the surrounding bone and undergo progressive impaction. Localization of PTHrP mRNA during normal tooth development by in situ hybridization reveals increasing levels of expression in the enamel epithelium before the formation of the eruption pathway. The type I PTH/PTHrP receptor is expressed in both the adjacent dental mesenchyme and in the alveolar bone. The replacement of PTHrP expression in the enamel epithelium with a keratin 14-driven transgene corrects the defect in bone resorption and restores the normal program of tooth eruption. PTHrP therefore represents an essential signal in the formation of the eruption pathway. PMID:9751753

  13. Synthesis of fully active biotinylated analogues of parathyroid hormone and parathyroid hormone-related protein as tools for the characterization of parathyroid hormone receptors.

    PubMed

    Roubini, E; Duong, L T; Gibbons, S W; Leu, C T; Caulfield, M P; Chorev, M; Rosenblatt, M

    1992-04-28

    The synthesis, purification, and characterization of biotinylated analogues of parathyroid hormone (PTH) and PTH-related protein (PTHrP) are described. A novel methodology was developed which allowed the selective biotinylation during solid-phase synthesis of either the Lys13 or Lys26 residue in PTH/PTHrP sequences. Incorporation of orthogonally protected N alpha-Boc-Lys(N epsilon-Fmoc) at a selected position in the sequence, followed by selective side-chain deprotection and biotinylation of the epsilon-amino group, permitted modification of the specific lysine only. Biotinylated analogues of [Nle8,18,Tyr34]bPTH(1-34)NH2 (analogue 1a) were prepared by modification of Lys13 with a biotinyl group (analogue 1) or a biotinyl-epsilon-aminohexanoyl group (analogue 2) or at Lys26 with a biotinyl-epsilon-aminohexanoyl group (analogue 3). A biotinylated PTHrP antagonist [Leu11,D-Trp12,Lys13(N epsilon-(biotinyl-beta-Ala))]PTHrP(7-34)NH2 (analogue 5), was also prepared. In a different synthetic approach, selective modification of the thiol group of [Cys35]PTHrP(1-35)NH2, in solution, with N-biotinyl-N'-(6-maleimidohexanoyl)hydrazide, resulted in analogue 4. The high affinities of the biotinylated analogues for PTH receptors present in human osteosarcoma B-10 cells or in porcine renal cortical membranes (PRCM), were comparable to those of the underivatized parent peptides. The analogues were also highly potent in stimulation of cAMP formation (analogues 1-4) or inhibition of PTH-stimulated adenylyl cyclase (analogue 5) in B-10 cells. The most potent analogue (analogue 1) had potencies in B-10 cells (Kb = 1.5 nM, Km = 0.35 nM) and in porcine renal membranes (Kb = 0.70 nM) identical or similar to those of its parent peptide, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1314656

  14. Intermittently Administered Parathyroid Hormone [1–34] Promotes Tendon-Bone Healing in a Rat Model

    PubMed Central

    Bi, Fanggang; Shi, Zhongli; Jiang, Shuai; Guo, Peng; Yan, Shigui

    2014-01-01

    The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1–34] (PTH[1–34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 μg PTH[1–34]/kg subcutaneously were given to the PTH group rats (n = 10) for four weeks, and the controls (n = 10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1–34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1–34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1–34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1–34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction. PMID:25268612

  15. Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

    1997-01-01

    To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

  16. Molecular recognition of parathyroid hormone by its G protein-coupled receptor

    SciTech Connect

    Pioszak, Augen A.; Xu, H. Eric

    2008-08-07

    Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-{angstrom} structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer {alpha}-{beta}-{beta}{alpha} fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.

  17. Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

    PubMed Central

    Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

    2014-01-01

    Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

  18. Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

    SciTech Connect

    Demay, M.; Mitchell, J.; Goltzman, D.

    1985-11-01

    The authors compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding.

  19. [Osteoporosis in Rheumatoid Arthritis: role of the vitamin D/parathyroid hormone system].

    PubMed

    Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

    2015-01-01

    Osteoporosis is a well-established extra-articular feature of Rheumatoid Arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression. PMID:25582993

  20. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  1. Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1.

    PubMed

    Zou, Dan; Silvius, Derek; Davenport, Julie; Grifone, Raphaelle; Maire, Pascal; Xu, Pin-Xian

    2006-05-15

    Previous studies have suggested a role of the homeodomain Six family proteins in patterning the developing vertebrate head that involves appropriate segmentation of three tissue layers, the endoderm, the paraxial mesoderm and the neural crest cells; however, the developmental programs and mechanisms by which the Six genes act in the pharyngeal endoderm remain largely unknown. Here, we examined their roles in pharyngeal pouch development. Six1-/- mice lack thymus and parathyroid and analysis of Six1-/- third pouch endoderm demonstrated that the patterning of the third pouch into thymus/parathyroid primordia is initiated. However, the endodermal cells of the thymus/parathyroid rudiments fail to maintain the expression of the parathyroid-specific gene Gcm2 and the thymus-specific gene Foxn1 and subsequently undergo abnormal apoptosis, leading to a complete disappearance of organ primordia by E12.5. This thus defines the thymus/parathyroid defects present in the Six1 mutant. Analyses of the thymus/parathyroid development in Six1-/-;Six4-/- double mutant show that both Six1 and Six4 act synergistically to control morphogenetic movements of early thymus/parathyroid tissues, and the threshold of Six1/Six4 appears to be crucial for the regulation of the organ primordia-specific gene expression. Previous studies in flies and mice suggested that Eya and Six genes may function downstream of Pax genes. Our data clearly show that Eya1 and Six1 expression in the pouches does not require Pax1/Pax9 function, suggesting that they may function independently from Pax1/Pax9. In contrast, Pax1 expression in all pharyngeal pouches requires both Eya1 and Six1 function. Moreover, we show that the expression of Tbx1, Fgf8 and Wnt5b in the pouch endoderm was normal in Six1-/- embryos and slightly reduced in Six1-/-;Six4-/- double mutant, but was largely reduced in Eya1-/- embryos. These results indicate that Eya1 appears to be upstream of very early events in the initiation of thymus/parathyroid

  2. 77 FR 14043 - Certain Mobile Devices, Associated Software, and Components Thereof; Determination To Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... COMMISSION Certain Mobile Devices, Associated Software, and Components Thereof; Determination To Review Final... certain mobile devices, associated software, and components thereof by reason of infringement of U.S... mobile devices, associated software, and components thereof containing same by reason of infringement...

  3. The combined effect of parathyroid hormone and bone graft on implant fixation

    PubMed Central

    Daugaard, H.; Elmengaard, B.; Andreassen, T. T.; Baas, J.; Bechtold, J. E.; Søballe, K.

    2013-01-01

    Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseo-integration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1-34) 5 μg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks. PMID:21196558

  4. Undescended parathyroid adenoma: an important etiology for failed operations for primary hyperparathyroidism.

    PubMed

    Fraker, D L; Doppman, J L; Shawker, T H; Marx, S J; Spiegel, A M; Norton, J A

    1990-01-01

    From July, 1982 to April, 1989, a total of 145 patients with persistent or recurrent primary hyperparathyroidism (HPT) were explored; 105 patients had an adenoma as the cause of HPT, and in 9 patients (9%), the abnormal gland was located at or superior to the carotid bifurcation (undescended parathyroid gland). These 9 patients had 14 prior explorations for HPT including 4 median sternotomies and 5 thyroidectomies. Each of the 9 patients was symptomatic of HPT, including bone disease in 8 of 9 patients and renal stones in 4 of 9 patients. Seven patients had an undescended parathyroid adenoma correctly localized preoperatively by ultrasound (n = 5), angiography (n = 5), venous sampling (n = 1), or computed tomography scan (n = 4). These 7 patients with accurate preoperative localization were explored by an incision anterior to the sternocleidomastoid muscle high in the neck that avoided the previous operative field and allowed rapid resection of the parathyroid adenoma. In the 2 patients who did not have accurate preoperative localization, the undescended adenoma was found after long tedious exploration including median sternotomy in 1 patient. Each patient (n = 9) who had an undescended parathyroid adenoma removed was cured of hypercalcemia, and 5 patients required postoperative 1,25-dihydroxy vitamin D3 for hypocalcemia. We conclude that undescended parathyroid adenomas comprise a significant proportion (9%) of adenomas during reoperations for persistent HPT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2368436

  5. Ultrastructural evaluation of parathyroid glands and thyroid C cells of cattle fed Solanum malacoxylon.

    PubMed Central

    Collins, W. T.; Capen, C. C.; Döbereiner, J.; Tokarnia, C. H.

    1977-01-01

    Fine structural alterations of thyroid C cells and parathyroid chief cells were evaluated after feeding dried leaves of the calcinogenic plant, Solanum malacoxylon, to cattle for 1, 6 and 32 days. Thyroid C cells initially were degranulated in response to the hypercalcemia, and parathyroid chief cells accumulated secretory granules. There was hypertrophy of thyroid C cells with well-developed secretory organelles but few secretory granules in the cytoplasm after 6 days of feeding S. malacoxylon. Inactive chief cells with dispersed profiles of endoplasmic reticulum and increased lysosomal bodies predominated in the parathyroid glands. Multiple foci of soft tissue mineralization were present in the heart, lung, and kidney. Thyroid C cells underwent hypertrophy and hyperplasia after 32 days of S. malacoxylon, and parathyroid chief cells were inactive or atrophic in response to the long-term hypercalcemia. Severe soft tissue mineralization was present throughout the cardiovascular system, lung, kidney, and spleen. These ultrastructural changes in thyroid C cells and parathyroid chief cells plus the widespread soft tissue mineralization observed after feeding cattle small amounts of S. malacoxylon are consistent with the recent evidence that leaves of this plant are a potent source of the active metabolite, 1,25-dihydroxycholecalciferol, of vitamin D. Images Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:869016

  6. Ultrastructural evaluation of parathyroid glands and thyroid C cells of cattle fed Solanum malacoxylon.

    PubMed

    Collins, W T; Capen, C C; Döbereiner, J; Tokarnia, C H

    1977-06-01

    Fine structural alterations of thyroid C cells and parathyroid chief cells were evaluated after feeding dried leaves of the calcinogenic plant, Solanum malacoxylon, to cattle for 1, 6 and 32 days. Thyroid C cells initially were degranulated in response to the hypercalcemia, and parathyroid chief cells accumulated secretory granules. There was hypertrophy of thyroid C cells with well-developed secretory organelles but few secretory granules in the cytoplasm after 6 days of feeding S. malacoxylon. Inactive chief cells with dispersed profiles of endoplasmic reticulum and increased lysosomal bodies predominated in the parathyroid glands. Multiple foci of soft tissue mineralization were present in the heart, lung, and kidney. Thyroid C cells underwent hypertrophy and hyperplasia after 32 days of S. malacoxylon, and parathyroid chief cells were inactive or atrophic in response to the long-term hypercalcemia. Severe soft tissue mineralization was present throughout the cardiovascular system, lung, kidney, and spleen. These ultrastructural changes in thyroid C cells and parathyroid chief cells plus the widespread soft tissue mineralization observed after feeding cattle small amounts of S. malacoxylon are consistent with the recent evidence that leaves of this plant are a potent source of the active metabolite, 1,25-dihydroxycholecalciferol, of vitamin D. PMID:869016

  7. Minimally invasive parathyroid surgery, the Norman 20% rule: is it valid?

    PubMed

    Quillo, Amy R; Bumpous, Jeffery M; Goldstein, Richard E; Fleming, Muffin M; Flynn, Michael B

    2011-04-01

    The 20 per cent rule proposed by Norman established a guideline using radioactivity in the minimally invasive radioguided parathyroidectomy (MIRP) technique to localize and confirm removal of an abnormal parathyroid gland in patients with primary hyperparathyroidism. If radioactivity in the resected gland was at least 20 per cent of excision site/background radioactivity, the 20 per cent rule was satisfied. Patients meeting these criteria underwent unilateral MIRP without intraoperative parathyroid hormone assay or intraoperative frozen section. The study aim was to independently evaluate the 20 per cent rule in MIRP patients with primary hyperparathyroidism. Using the University of Louisville Parathyroid Database from January 1, 1999 to December 31, 2007, 216 MIRP patients with complete radioguided and postoperative management data were identified. The average percentage of ex vivo parathyroid gland radioactivity compared with excision site/background radioactivity was 107 per cent with a range from 14 to 388 per cent. For 99 per cent (196/198) radioactivity recorded from the excised gland was at least 20 per cent of radioactivity recorded from the excision site. Normocalcemia was documented in 98.5 per cent (195/198) at 12 month follow-up. Our data supports the 20 per cent rule in that in 99 per cent of MIRP patients the resected gland radioactivity was at least 20 per cent of excision site radioactivity allowing localization and confirmation of an overactive gland without intraoperative parathyroid hormone monitoring or tissue analysis. PMID:21679561

  8. Osteosclerotic and osteolytic manifestations of hyperparathyroidism in a case of Tc99m SestaMIBI positive parathyroid adenoma

    PubMed Central

    Das, Kalpa Jyoti; Sehgal, Aditi Khurana; Jaiman, Ashish; Sethi, Ravinder Singh

    2015-01-01

    Primary hyperparathyroidism is the first differential diagnosis when a patient presents with asymptomatic hypercalcemia. The symptoms of hyperparathyroidism can be as grave as skeletal, cardiovascular, and neuropsychological changes. Skeletal manifestations are relatively common, and patient may present with generalized or focal bone pains, fragility fractures, subperiosteal bone resorption, and osteolytic lesions like brown tumors and salt and pepper appearance of the skull. However, focal osteosclerotic lesions of the skull are rare findings in hyperparathyroidism. Only a few cases of associated osteosclerosis are reported in the literature. Here, we report a case of Tc99m SestaMIBI positive parathyroid adenoma with coexisting osteolytic and osteosclerotic skull lesions on Tc99m methylene diphosphonate bone scan. PMID:26170573

  9. Parathyroid autotransplantation in extensive head and neck resections: case series report

    PubMed Central

    2011-01-01

    Permanent or temporary hypoparathyroidism may be a debilitating result of radical cervical surgery, as noted most commonly following thyroid or parathyroid surgery. However, it can also be the outcome of any surgical procedure involving bilateral extensive manipulation of the anterior neck triangle, especially in order to ensure oncologically adequate surgical margins. We report our experience of three patients that underwent parathyroid immediate autotransplanation following extensive surgical manipulations of the neck region for oncological reasons. PTH levels were restored to normal by the fourth postoperative week, allowing us to wean the patients off calcium and vitamin D3 supplementation, which was attributed to full autograft function. Parathyroid autotransplantation, immediate or delayed, is a simple and safe technique which should be considered by the surgeon whenever there is a high risk for postoperative hypoparathyroidism following radical operations of the neck for oncological reasons. PMID:22085420

  10. Thallium-pertechnetate subtraction scanning in the preoperative localization of an ectopic undescended parathyroid gland.

    PubMed

    Frydman, James; Bianco, Jesus; Drezner, Marc; Chen, Herbert

    2004-09-01

    Although bilateral exploration is highly effective in the treatment of primary hyperparathyroidism, minimally invasive parathyroidectomy has evolved into the procedure of choice when a single parathyroid lesion can be localized preoperatively. In this article, we discuss the utilization of thallium-pertechnetate subtraction scanning (TPSS) after technetium Tc-99m sestamibi scintigraphy failed to localize an ectopic parathyroid adenoma. Subsequently, radioguided resection of an undescended parathyroid adenoma inferior to the left submandibular gland was performed with surgical cure after a single procedure. This case report illustrates the importance of TPSS as a second-line modality in preoperative adenoma localization, thereby using minimally invasive techniques to successfully treat this patient's primary hyperparathyroidism. PMID:15311119

  11. Recurrent hyperparathyroidism due to proliferation of autotransplanted parathyroid tissue in a multiple endocrine neoplasia type 2A patient.

    PubMed

    Kim, Bong Kyun; Lee, Jina; Sun, Woo Young

    2016-09-01

    About 20%-30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is accompanied by primary hyperparathyroidism. These patients undergo parathyroidectomy and, if needed, autotransplantation. In rare cases, autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure of transplantation or hyperparathyroidism due to proliferation of the transplanted tissue. A 68-year-old female with MEN 2A underwent left adrenalectomy for pheochromocytoma 15 years prior to presentation and total thyroidectomy, central and right lateral neck lymph node dissection, and subtotal parathyroidectomy with autotransplantation for medullary thyroid cancer and primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid adenoma was detected in the left sternocleidomastoid muscle on ultrasonography and on an additional sestamibi scan. The mass was excised and histologically confirmed as parathyroid adenoma. This is a very rare case, and it suggests that long-term regular monitoring of serum calcium and intact parathyroid hormone levels is necessary after parathyroid autotransplantation. PMID:27617256

  12. Recurrent hyperparathyroidism due to proliferation of autotransplanted parathyroid tissue in a multiple endocrine neoplasia type 2A patient

    PubMed Central

    Kim, Bong Kyun; Lee, Jina

    2016-01-01

    About 20%–30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is accompanied by primary hyperparathyroidism. These patients undergo parathyroidectomy and, if needed, autotransplantation. In rare cases, autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure of transplantation or hyperparathyroidism due to proliferation of the transplanted tissue. A 68-year-old female with MEN 2A underwent left adrenalectomy for pheochromocytoma 15 years prior to presentation and total thyroidectomy, central and right lateral neck lymph node dissection, and subtotal parathyroidectomy with autotransplantation for medullary thyroid cancer and primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid adenoma was detected in the left sternocleidomastoid muscle on ultrasonography and on an additional sestamibi scan. The mass was excised and histologically confirmed as parathyroid adenoma. This is a very rare case, and it suggests that long-term regular monitoring of serum calcium and intact parathyroid hormone levels is necessary after parathyroid autotransplantation.

  13. Parathyroid Hormone–Related Protein Promotes Epithelial–Mesenchymal Transition

    PubMed Central

    Ardura, Juan Antonio; Rayego-Mateos, Sandra; Rámila, David; Ruiz-Ortega, Marta

    2010-01-01

    Epithelial–mesenchymal transition (EMT) is an important process that contributes to renal fibrogenesis. TGF-β1 and EGF stimulate EMT. Recent studies suggested that parathyroid hormone–related protein (PTHrP) promotes fibrogenesis in the damaged kidney, apparently dependent on its interaction with vascular endothelial growth factor (VEGF), but whether it also interacts with TGF-β and EGF to modulate EMT is unknown. Here, PTHrP(1-36) increased TGF-β1 in cultured tubuloepithelial cells and TGF-β blockade inhibited PTHrP-induced EMT-related changes, including upregulation of α-smooth muscle actin and integrin-linked kinase, nuclear translocation of Snail, and downregulation of E-cadherin and zonula occludens-1. PTHrP(1-36) also induced EGF receptor (EGFR) activation; inhibition of protein kinase C and metalloproteases abrogated this activation. Inhibition of EGFR activation abolished these EMT-related changes, the activation of ERK1/2, and upregulation of TGF-β1 and VEGF by PTHrP(1-36). Moreover, inhibition of ERK1/2 blocked EMT induced by either PTHrP(1-36), TGF-β1, EGF, or VEGF. In vivo, obstruction of mouse kidneys led to changes consistent with EMT and upregulation of TGF-β1 mRNA, p-EGFR protein, and PTHrP. Taken together, these data suggest that PTHrP, TGF-β, EGF, and VEGF might cooperate through activation of ERK1/2 to induce EMT in renal tubuloepithelial cells. PMID:19959711

  14. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    PubMed Central

    Dobolyi, Arpád; Dimitrov, Eugene; Palkovits, Miklós; Usdin, Ted B.

    2012-01-01

    The G-protein coupled parathyroid hormone 2 receptor (PTH2R) is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand, tuberoinfundibular peptide of 39 residues (TIP39), is synthesized in only two brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine-vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control neuroendocrine disorders

  15. Role of Histological Criteria and Immunohistochemical Markers in Predicting Risk of Malignancy in Parathyroid Neoplasms.

    PubMed

    Kumari, Niraj; Chaudhary, Nandita; Pradhan, Roma; Agarwal, Amit; Krishnani, Narendra

    2016-06-01

    Parathyroid carcinoma (PC) is a rare neoplasm accounting for 0.5-6 % of primary hyperparathyroidism. Histological criteria are currently considered as established means to diagnose malignancy in parathyroid neoplasms; however, it does not accurately predict the risk of aggressive behaviour of PC. Immunohistochemical (IHC) markers have been used in the literature with variable results. This work was planned to study whether IHC markers would have any added advantage over histology in predicting outcome in parathyroid neoplasms. Two hundred twenty-seven parathyroid neoplasms were reviewed according to older and revised histological criteria. IHC was performed for parafibromin, APC, galectin-3, PGP9.5 and Ki67. Diagnostic categories were correlated with clinical, biochemical, histological features and IHC markers. Chi-square test was used to analyse categorical variables. Review of histology by earlier and revised criteria showed a change in diagnosis of five cases of atypical adenoma (15.1 %), all of which were diagnosed as carcinoma according to earlier criteria. Change in diagnosis did not affect behaviour of disease as none of the cases showed recurrence or metastasis on follow-up. Combination of PF, Gal-3 and PGP9.5 showed 50 % sensitivity, 97.9 % specificity and 95.4 % predictive accuracy for PC. Histological criteria still remains the most established method for predicting risk of malignancy in parathyroid neoplasms irrespective of whether old or revised criteria are used. Combination of positive (Gal-3, PGP9.5) and negative (PF) IHC markers may be used as an adjunct to histology in histological, atypical and malignant parathyroid neoplasms to obviate the need for repeated follow-up. PMID:26984237

  16. Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

    PubMed Central

    Deshpande, Sagar S.; Gallagher, Katherine K.; Donneys, Alexis; Tchanque-Fossuo, Catherine N.; Sarhaddi, Deniz; Nelson, Noah S.; Chepeha, Douglas B.; Buchman, Steven R.

    2015-01-01

    Objective Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Methods Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 μg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Results Parathyroid hormone–treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. Conclusions The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration–approved drug on formulary, significantly improve outcomes in a model of

  17. Application of carbon nanoparticles for parathyroid protection in reoperation of thyroid diseases

    PubMed Central

    Gao, Bo; Tian, Wuguo; Jiang, Yan; Zhang, Shu; Guo, Lingji; Zhao, Jianjie; Zhang, Gang; Hao, Shuai; Xu, Yan; Luo, Donglin

    2015-01-01

    Objective: To explore a new identification and protection method of the parathyroid gland in reoperation for thyroid diseases. Method: 54 patients receiving reoperation for thyroid diseases were selected. The experiment group intraoperatively adopted carbon nanoparticles suspension for negative development of the parathyroid gland, whereas the control group did not use carbon nanoparticles suspension. Results: At 48 h after surgery, the parathyroid hormone level was lower than the normal state in 9 patients (33.30%) of the control group and 1 patient (3.70%) of the experiment group; meanwhile, 6 months after surgery, 8 patients of the control group (29.63%) and 1 patient of the experiment group (3.70%) showed a lower level than the normal state with statistical differences. The serum calcium level in 10 patients of the control group (37.04%) and 2 patients of the experiment group (7.41%) was lower than the normal state at 48 h after surgery, while a lower level than the normal state was also shown in 8 patients of the control group (29.63%) and 1 patient of the experiment group (3.70%) 6 months after surgery with statistically significant between the two groups. A total of 10 (37.04%) and 1 parathyroid gland (3.70%) were detected with a statistical difference in both groups. Conclusion: By adopting carbon nanoparticles in reoperation for the thyroid diseases and negative development of the parathyroid gland for identification and protection of the parathyroid gland, the incidence of hypoparathyroidism is reduced effectively, thus improving the postoperative quality of life of the patients. PMID:26885201

  18. Localization of Parathyroid Adenoma With Real-Time Ultrasound: Freehand SPECT Fusion.

    PubMed

    Bluemel, Christina; Kirchner, Paul; Kajdi, Georg W; Werner, Rudolf A; Herrmann, Ken

    2016-03-01

    Preoperative localization of parathyroid adenoma in primary hyperparathyroidism gains in importance as there is a trend toward minimally invasive parathyroid surgery. Besides MRI, 4-dimensional CT, PET/CT, invasive-selective venous sampling, or angiography, both ultrasound and scintigraphy are standard of care for lesion localization. Here we report on a 53-year-old woman with suspicion of primary hyperparathyroidism using real-time fusion of scintigraphic (freehand SPECT) and ultrasound imaging for adenoma localization. Real-time fusion of ultrasound and freehand SPECT allowed noninvasive dedicated metabolic and anatomic adenoma localization and treatment planning. PMID:26284776

  19. Incidental finding of parathyroid adenoma with 11C-choline PET/CT.

    PubMed

    Mapelli, Paola; Busnardo, Elena; Magnani, Patrizia; Freschi, Massimo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina

    2012-06-01

    Positron emission tomography/computed tomography (PET/CT) with 11C-choline is an established diagnostic tool for restaging prostate cancer patients with biochemical failure after primary treatment. In the present case, 11C-choline PET/CT was performed in a prostate cancer patient with skeletal metastases, treated with hormonal therapy. In addition to the detection of pathologic uptake at prostate and vertebra, 11C-choline uptake occurred in the neck. The finding was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally confirmed by parathyroid scintigraphy and histopathological analysis performed after hemithyroidectomy. PMID:22614195

  20. [The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study].

    PubMed

    Chen, X Y; Tang, Z L

    2016-06-01

    Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years. PMID:27256534

  1. The Vitamin D, Ionised Calcium and Parathyroid Hormone Axis of Cerebral Capillary Function: Therapeutic Considerations for Vascular-Based Neurodegenerative Disorders

    PubMed Central

    Lam, Virginie; Takechi, Ryusuke; Pallabage-Gamarallage, Menuka; Giles, Corey; Mamo, John C. L.

    2015-01-01

    Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular

  2. Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts.

    PubMed

    Huang, Michael S; Morony, Sean; Lu, Jinxiu; Zhang, Zina; Bezouglaia, Olga; Tseng, Wendy; Tetradis, Sotirios; Demer, Linda L; Tintut, Yin

    2007-07-20

    Cardiovascular disease, such as atherosclerosis, has been associated with reduced bone mineral density and fracture risk. A major etiologic factor in atherogenesis is believed to be oxidized phospholipids. We previously found that these phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal cells, suggesting that they may account for the clinical link between atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone formation are increasingly used as a new treatment for osteoporosis. It is not known, however, whether atherogenic phospholipids alter the effects of bone anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH-induced cAMP production and expression of immediate early genes Nurr1 and IL-6. Results from immunofluorescence and Western blot analyses showed that inhibitory effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD 1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin expression, and SMAD activation. These results suggest that atherogenic lipids inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility that hyperlipidemia and atherogenic phospholipids may interfere with anabolic therapy. PMID:17522049

  3. Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.

    PubMed

    Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A

    2016-06-01

    Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility. PMID:26847434

  4. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 μg/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

  5. Effect of 131I ‘clear residual thyroid tissue’ after surgery on the function of parathyroid gland in differentiated thyroid cancer

    PubMed Central

    ZHAO, ZHI-HUA; LI, FENG-QI; HAN, JIAN-KUI; LI, XIAN-JUN

    2015-01-01

    Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) ‘clear residual thyroid tissue’ following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I ‘clear residual thyroid tissue’ treatment and underwent a whole body scan after 1 week to determine whether ‘clear residual thyroid tissue’ treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I ‘clear residual thyroid tissue’ treatment did not significantly impair the parathyroid function, thereby improving the treatment effect. PMID:26668598

  6. A novel single-molecule study to determine protein--protein association constants.

    PubMed

    Ratcliff, G C; Erie, D A

    2001-06-20

    Atomic force microscopy (AFM) is traditionally used as an imaging technique to gain qualitative information for a biological system. We have successfully used the imaging capabilities of the AFM to determine protein-protein association constants. We have developed a method to measure the molecular weight of a protein based on its volume determined from AFM images. Our volume determination method allows for rapid, accurate analysis of large protein populations. On the basis of the measured volume, the fraction of monomers as dimers was determined for the DNA helicase UvrD, and the dissociation constant (K(d)) for the helicase was calculated. We determined a K(d) for UvrD of 1.4 microM, which is in good agreement with published K(d) data obtained from analytical ultracentrifugation (AUC) studies. Our method provides a rapid method for determining protein-protein association constants. PMID:11403593

  7. Parathyroid imaging: comparison of double-tracer (T1-201, Tc-99m) scintigraphy and high-resolution US

    SciTech Connect

    Gooding, G.A.; Okerlund, M.D.; Stark, D.D.; Clark, O.H.

    1986-10-01

    Parathyroid scintigraphy using a double-tracer (T1-201, Tc-99m) subtraction technique depicted 17 of 23 (74%) parathyroid adenomas in patients with and without previous neck operations. High-resolution (10-MHz) ultrasound (US) depicted 18 (78%) of these adenomas. Average tumor size depicted by US was 17 X 10 X 8 mm (excluding a giant adenoma) and 19 X 10 X 9 mm by scintigraphy. Alone, neither modality was particularly sensitive in the depiction of primary hyperplasia of the parathyroid glands, but combined techniques were more effective than the use of a single modality. With both US and T1-201 scintigraphy, only two of 23 cases of parathyroid adenoma in the neck were missed, and none of the eight cases of secondary hyperplasia were missed. In 11 patients who had previously undergone neck surgery, parathyroid tumors were identified in eight by either US or double-tracer scintigraphy. Preoperative parathyroid imaging with double-tracer scintigraphy and high-resolution US is suggested for patients with hyperparathyroidism, particularly in those patients who have had previous parathyroid surgery.

  8. Serum parathyroid hormone-related protein concentration in a dog with a thymoma and persistent hypercalcemia.

    PubMed Central

    Foley, P; Shaw, D; Runyon, C; McConkey, S; Ikede, B

    2000-01-01

    A thymoma was tentatively diagnosed by radiographic and cytologic examination in a dog with hypercalcemia and elevated serum parathyroid hormone-related protein (PTHrP) concentration. Following surgical excision, the diagnosis of thymoma was confirmed via histopathologic examination, the hypercalcemia resolved, and the PTHrP concentration decreased to below detectable limits. Images Figure 1. Figure 2. PMID:11126493

  9. Video assisted thoracoscopic excision of mediastinal ectopic parathyroid adenomas: a UK regional experience

    PubMed Central

    Khan, Ali Zamir; Rew, David; Lagattolla, Nicholas; Singh, Neeta

    2015-01-01

    Background To report the first series of video-assisted thoracoscopic surgery (VATS) resection of mediastinal ectopic parathyroid adenomas (MEPAs) in the UK. Methods A case series of seven cases undergoing VATS between 2004 and 2009 to treat single gland hyperparathyroidism. Methylene blue (MB) was used in 5/7 cases immediately before exploration to identify the adenomas. Carbon dioxide (CO2) up to pressures of 10 mmHg was used safely to deflate the lung in two cases. Results There were five women and two men with a mean age of 53 years (range, 27-72 years). Histopathology confirmed successful resection of the parathyroid adenoma in 6/7 cases. There was one conversion to open thoracotomy due to bleeding from the azygos vein resulting from excessive traction. Despite marked MB uptake, this patient proved to have tuberculoid adenopathy and no parathyroid tissue was identified. Postoperative plasma calcium returned to normal in 6/7 patients and parathyroid hormone (PTH) level in 6/7 patients. The median hospital stay was 2 days and there was no mortality in this series. Conclusions MEPAs can be safely resected using VATS with minimal surgical morbidity, short drainage time and short hospital stay. CO2 insufflation and the intraoperative use of MB are safe and help to accurately localise the ectopic adenoma. VATS should be considered as the first-line approach for resection of MEPAs. PMID:26693148

  10. [Complex ultrasonic study of parathyroids in diagnostic and surgical treatment of primary hyperparathyroidism].

    PubMed

    Chernousov, A F; Ippolitov, L I; Musaev, G Kh; Saliba, M B

    2014-01-01

    Primary hyperparathyroidism is the most common disease in Russian Federation, cured by endocrine surgeons. Health status after surgical correction of primary hyperparathyroidism depends on availability of screening hypercalciemia, which is still absent in our country. Another problem is a model of surgical management of primary hyperparathyroidism (frozen section, intraoperative monitoring of parathyroid hormone, gamma-detection and so on). Although minimally invasive parathyroidectomy has become the only method of treatment in many countries, it is still crucial to identify and accurately localize parathyroid glands before bilateral neck exploration surgery. The diagnostic efficacy of the various imaging techniques is still the subject of current debate. The usefulness of preoperative parathyroid imaging with both dual scintigraphy-single-photon emission computed tomography (SPECT) Tc 99m and high-resolution ultrasonography (US) was studied in 92 patients undergoing operations for primary hyperparathyroidism. The accuracy of "integrated" ultrasonography ("check-up US", "target US" after SPECT) and "intraoperative US") of parathyroid glands was 92.9%, sensitivity - 91% and positive predictive value - 94%. This study supports an algorithm of obtaining "integrated" ultrasonography as the initial and in most cases the only preoperative localization tests for patients with primary hyperparathyroidism. PMID:25042185

  11. Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation.

    PubMed

    Touska, Philip; Srikanthan, Ahgi; Amarasinghe, Kavita; Jawad, Susan

    2016-01-01

    A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article. PMID:27440844

  12. Preoperative localization of parathyroid lesion: diagnostic usefulness of color doppler ultrasonography

    PubMed Central

    mohammadi, Afshin; Moloudi, Farzad; Ghasemi-rad, Mohammad

    2012-01-01

    Introduction Recently, minimally invasive parathyroidectomy (MIP) has been developed and is gaining popularity among surgeons. For this reason, preoperative localization is playing an important role to detect the precise location of the affected gland and to increase the success rate. Material and methods From June 2007 to June 2011, 56 consecutive patients (11 men and 45 women) with primary or secondary hyperparathyroidism in our center underwent Gray scale, color Doppler and 99m-Tc MIBI scan prior to operative management of parathyroid lesions. Results The sensitivity, specificity and accuracy of US and MIBI scan for pHPT was 88%, 94%, 91% and 70%, 100% and 85% respectively. In patients with sHPT, the sensitivity, specificity and accuracy of US and MIBI scan was 54%, 93%, 76% and 25%, 100% and 72.9% respectively. The overall sensitivity of combined US and MIBI scan in pHPT and sHPT was 97% and 45% respectively. The overall sensitivity, specificity and accuracy of CDUS in diagnosis of parathyroid lesions in pHPT and sHPT is 97%, 100%, 98.6% and 62%, 100% and 83% respectively. Conclusion The overall sensitivity and specificity of US and MIBI in preoperative localization of parathyroid adenoma in sHPT is lower than pHPT and performing CDUS can increases the overall sensitivity and specificity of imaging methods in accurate localization of parathyroid lesion. PMID:22328952

  13. Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

    PubMed Central

    Sellers, R S; Luchin, A I; Richard, V; Brena, R M; Lima, D; Rosol, T J

    2011-01-01

    Parathyroid hormone-related protein (PTHrP) is a multifunctional protein that is often dysregulated in cancer. The human PTHrP gene is alternatively spliced into three isoforms, each with a unique 3′-untranslated region (3′-UTR), encoding 139, 173 and 141 amino acid proteins. The regulation of PTHrP mRNA isoform expression has not been completely elucidated, but it may be affected by transforming growth factor-β1 (TGF-β1). In this study, we examined differences in the PTHrP mRNA isoform expression in two squamous carcinoma cell lines (SCC2/88 and HARA), an immortalized keratinocyte cell line (HaCaT), and spontaneous human lung cancer with adjacent normal tissue. In addition, the effect of TGF-β1 on PTHrP mRNA isoform expression and stability was examined. Cell-type specific expression of PTHrP mRNA isoforms occurred between the various cell lines, normal human lung, and immortalized human keratinocytes (HaCaT). PTHrP isoform expression pattern was significantly altered between normal lung tissue and the adjacent lung cancer. In vitro studies revealed that TGF-β1 differentially altered the mRNA steady-state levels and mRNA stability of the PTHrP isoforms. Protein–RNA binding studies identified different proteins binding to the 3′-UTR of the PTHrP isoforms (139) and (141), which may be important in the differential mRNA stability and response to cytokines between the PTHrP isoforms. The data demonstrate that there is cell-type specific expression of PTHrP mRNA isoforms, and disruption of the normal regulation during cancer progression may in part be associated with TGF-β1-induced changes in PTHrP mRNA isoform expression and stability. PMID:15291755

  14. A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma.

    PubMed Central

    Jaskowiak, N; Norton, J A; Alexander, H R; Doppman, J L; Shawker, T; Skarulis, M; Marx, S; Spiegel, A; Fraker, D L

    1996-01-01

    OBJECTIVES: The authors evaluate the results of preoperative imaging protocols and surgical re-exploration in a series of patients with missed parathyroid adenomas after failed procedures for primary hyperparathyroidism. BACKGROUND: The success rate is lower and the complication rate is increased in patients undergoing reoperation for primary hyperparathyroidism compared with initial procedures. Scarring and distortion of tissue planes plus the potential for ectopic gland location leads to this worsened outcome. METHODS: Two hundred eighty-eight consecutive patients with persistent/recurrent hyperparathyroidism were treated at a single institution after a failed procedure or procedures at outside institutions. Two hundred twenty-two of these patients (77%) were believed to have a missed single adenoma, and these patients underwent 228 operations and 227 preoperative work-ups. Preoperative evaluation consisted of a combination of four noninvasive imaging studies--neck ultrasound, nuclear medicine scan, neck and mediastinal computed tomography scan, and neck and mediastinal magnetic resonance imaging. Based on the noninvasive testing alone, 27% patients underwent surgery whereas the other patients underwent invasive studies, including selective angiography (58%), selective venous sampling for parathyroid hormone (43%), or percutaneous aspiration of suspicious lesions (15%). RESULTS: Abnormal parathyroid adenomas were found in 209 of 222 initial procedures and 6 of 6 second procedures, with an overall success rate in terms of resolution of hypercalcemia in 97% (215/222) of patients. The single most common site of missed adenoma glands was in the tracheal-esophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%). The most sensitive and specific noninvasive imaging test is the sestamibi

  15. Systemic but No Local Effects of Combined Zoledronate and Parathyroid Hormone Treatment in Experimental Autoimmune Arthritis

    PubMed Central

    Keller, Kresten Krarup; Thomsen, Jesper Skovhus; Stengaard-Pedersen, Kristian; Hauge, Ellen-Margrethe

    2014-01-01

    Introduction Local bone erosions and osteoporosis in rheumatoid arthritis (RA) are the result of a more pronounced bone resorption than bone formation. Present treatment strategies for RA inhibit inflammation, but do not directly target bone erosions. The aim of the study was in experimental arthritis to investigate the juxtaarticular and systemic effects of simultaneous osteoclast inhibition with zoledronate (ZLN) and osteoblast stimulation with parathyroid hormone (PTH). Methods Arthritis was induced in 36 SKG mice. The mice were randomized to three treatment groups and an untreated group: ZLN, PTH, PTH+ZLN, and untreated. Arthritis score and ankle width measurements were performed. Histological sections were cut from the right hind paw, and design-based stereological estimators were used to quantify histological variables of bone volume and bone formation and resorption. The femora were DXA- and μCT-scanned, and the bone strength was determined at the femoral neck and mid-diaphysis. Results Locally, we found no differences in arthritis score or ankle width throughout the study. Similarly, none of the treatments inhibited bone erosions or stimulated bone formation in the paw. Systemically, all treatments improved bone mineral density, strength of the femoral neck and mid-diaphysis, and μCT parameters of both cortical and trabecular bone. In addition, there was an additive effect of combination treatment compared with single treatments for most trabecular parameters including bone mineral density and bone volume fraction. Conclusions No local effect on bone was found by the combined action of inhibiting bone resorption and stimulating bone formation. However, a clear systemic effect of the combination treatment was demonstrated. PMID:24637846

  16. Dual-phase 99mTc-MIBI imaging findings in sporadic primary hyperplasia of parathyroid glands.

    PubMed

    Yang, Qi-Sheng; Wang, Chang-Yin; Wang, Bi-Cheng

    2015-05-01

    Primary hyperplasia of parathyroid is uncommon and rarely documented in literatures. We report an 18-year-old female patient with hyperparathyroidism due to unifocal primary hyperplasia of parathyroid glands. Dual-phase Tc-MIBI imaging was performed for this patient. We found remarkably increased MIBI uptake in the hyperplastic lesion in early imaging and no extinction of the uptake in delayed imaging. These results suggest that the dual-phase Tc-MIBI imaging is useful in localizing the hyperfunctioning lesions of primary hyperplasia of parathyroid glands. PMID:25706786

  17. Calcium mobilization from fish scales is mediated by parathyroid hormone related protein via the parathyroid hormone type 1 receptor.

    PubMed

    Rotllant, J; Redruello, B; Guerreiro, P M; Fernandes, H; Canario, A V M; Power, D M

    2005-12-15

    The scales of bony fish represent a significant reservoir of calcium but little is known about their contribution, as well as of bone, to calcium balance and how calcium deposition and mobilization are regulated in calcified tissues. In the present study we report the action of parathyroid hormone-related protein (PTHrP) on calcium mobilization from sea bream (Sparus auratus) scales in an in vitro bioassay. Ligand binding studies of piscine 125I-(1-35(tyr))PTHrP to the membrane fraction of isolated sea bream scales revealed the existence of a single PTH receptor (PTHR) type. RT-PCR of fish scale cDNA using specific primers for two receptor types found in teleosts, PTH1R, and PTH3R, showed expression only of PTH1R. The signalling mechanisms mediating binding of the N-terminal amino acid region of PTHrP were investigated. A synthetic peptide (10(-8) M) based on the N-terminal 1-34 amino acid residues of Fugu rubripes PTHrP strongly stimulated cAMP synthesis and [3H]myo-inositol incorporation in sea bream scales. However, peptides (10(-8) M) with N-terminal deletions, such as (2-34), (3-34) and (7-34)PTHrP, were defective in stimulating cAMP production but stimulated [3H]myo-inositol incorporation. (1-34)PTHrP induced significant osteoclastic activity in scale tissue as indicated by its stimulation of tartrate-resistant acid phosphatase. In contrast, (7-34)PTHrP failed to stimulate the activity of this enzyme. This activity could also be abolished by the adenylyl cyclase inhibitor SQ-22536, but not by the phospholipase C inhibitor U-73122. The results of the study indicate that one mechanism through which N-terminal (1-34)PTHrP stimulates osteoclastic activity of sea bream scales, is through PTH1R and via the cAMP/AC intracellular signalling pathway. It appears, therefore, that fish scales can act as calcium stores and that (1-34)PTHrP regulates calcium mobilization from them; it remains to be established if this mechanism contributes to calcium homeostasis in vivo

  18. Minerals, vitamin D, and parathyroid hormone in continuous ambulatory peritoneal dialysis.

    PubMed

    Delmez, J A; Slatopolsky, E; Martin, K J; Gearing, B N; Harter, H R

    1982-06-01

    The effects of continuous ambulatory peritoneal dialysis on parathyroid hormone (PTH) and mineral metabolism were evaluated in ten patients. Utilizing a PTH radioimmunoassay, which measures both intact hormone and carboxyl-terminal PTH fragments, it was found that the mean clearance of immunoreactive parathyroid hormone was 1.5 +/- 0.73 ml/min (SEM) yielding a daily net removal of 13.6 +/- 3.2% of estimated total extracellular parathyroid hormone. Gel electrophoresis of the dialysate revealed the presence of both intact parathyroid hormone and fragments in a similar pattern to that of peripheral plasma. Normal levels of 25-(OH) vitamin D and vitamin D binding protein were observed prior to the initiation of continuous ambulatory peritoneal dialysis and following 6 months of treatment. Timed dialysate collections (N = 93) demonstrated a daily calcium influx of only 9.9 +/- 9.7 mg. The daily removal of phosphorus was 308.4 +/- 15.5 mg. Despite elevated serum magnesium levels in all patients, the net daily removal was inadequate (31.2 +/- 15.5 mg). It was concluded that: (1) Unlike chronic hemodialysis, continuous ambulatory peritoneal dialysis removes significant amounts of parathyroid hormone. (2) Normal 25-(OH) vitamin D and vitamin D binding protein levels are maintained with continuous ambulatory peritoneal dialysis despite large protein losses. (3) Substantial amounts of phosphorus are removed with continuous ambulatory peritoneal dialysis but not to an extent that precludes use of phosphorus binders. (4) Dialysate containing lower magnesium and possibly higher calcium concentrations should be made available to improve mineral homeostasis. PMID:6897087

  19. Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59

    PubMed Central

    Li, Min; Dai, Yingxin; Zhu, Yuanjun; Fu, Chih-Lung; Tan, Vee Y.; Wang, Yanan; Wang, Xing; Hong, Xufen; Liu, Qian; Li, Tianming; Qin, Juanxiu; Ma, Xiaowei; Fang, Jingyuan; Otto, Michael

    2016-01-01

    Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin, and PSMα to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants. PMID:27296890

  20. Determining the significance of associations between two series of discrete events : bootstrap methods /

    SciTech Connect

    Niehof, Jonathan T.; Morley, Steven K.

    2012-01-01

    We review and develop techniques to determine associations between series of discrete events. The bootstrap, a nonparametric statistical method, allows the determination of the significance of associations with minimal assumptions about the underlying processes. We find the key requirement for this method: one of the series must be widely spaced in time to guarantee the theoretical applicability of the bootstrap. If this condition is met, the calculated significance passes a reasonableness test. We conclude with some potential future extensions and caveats on the applicability of these methods. The techniques presented have been implemented in a Python-based software toolkit.

  1. Determination of organic inorganic associations of trace elements in New Albany shale kerogen

    SciTech Connect

    Mercer, G.E.; Filby, R.H. )

    1989-03-01

    The inorganic and organic trace element associations in the kerogen isolated from the New Albany shale were studied by analysis of kerogen fractions and a mineral residue obtained using density separations. Elemental mass balance data from these fractions indicate a predominantly inorganic association with pyrite and marcasite for several elements (As, Co, Ga, Mn, Ni, Sb and Se). The degree of inorganic association of these elements was determined by treatment of the mineral residue ({approximately}85% FeS{sub 2}) with dilute HNO{sub 3} to remove pyrite and marcasite. The association of several other elements in minerals which are insoluble in dilute HNO{sub 3} (rutile, zircon, etc.) were also determined. The results of these studies indicate an essentially total organic association for V and approximately 95% organic association for Ni in New Albany kerogen. The determination of organically combined elements is very difficult for those elements which are predominantly concentrated in the mineral fraction. Correction methods based on low temperature ashing, chemical removal of pyrite, and physical methods of separation are compared.

  2. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  3. Parathyroid imaging: how good is it and how should it be done?

    PubMed

    Kettle, Andrew G; O'Doherty, Mike J

    2006-07-01

    Hypersecretion of parathormone in primary hyperparathyroidism is common, occurring in approximately 1 in 500 women and 1 in 2,000 men per year in their fifth to seventh decades of life. This has been suggested from the literature to be primarily the result of a parathyroid adenoma (80-85% of cases), hyperplasia involving more than 1 gland, usually with all 4 glands being involved (10-15% of cases), or the result, albeit rarely, of parathyroid carcinoma (0.5-1% of cases). Surgical removal of the hypersecreting gland is the primary treatment; this procedure is best performed by a skilled surgeon who would normally find the abnormality in 95% of cases. Imaging, however, should be used to identify the site of abnormality, potentially reducing inpatient stay and improving the patient experience. Functional imaging of parathyroid tissue using thallium was introduced in the 1980s but has largely been superceded by the use of (99m)Tc-labeled isonitriles. The optimum techniques have used (99m)Tc-sestamibi with subtraction imaging or washout imaging. A recent systematic review reported the percentage sensitivity (95% confidence intervals) for sestamibi in the identification of solitary adenomas as 88.44 (87.48-89.40), multigland hyperplasia 44.46 (41.13-47.8), double adenomas 29.95 (-2.19 to 62.09), and carcinoma 33 (33). This review does not separate the washout and subtraction techniques. The subtraction technique using (99m)Tc-sestamibi and (123)I is the optimal technique enabling the site to be related to the thyroid tissue when the parathyroid gland is in the neck in a normal position. If there is an equivocal scan then confirmation with high resolution ultrasound should be used. With ectopic glands, the combined use of single-photon emission computed tomography may then provide anatomical information to enable localization of the functional abnormality. In patients who have had surgical exploration by an experienced parathyroid surgeon in a unit with an experienced

  4. Determination of Secondary School Students' Cognitive Structure, and Misconception in Ecological Concepts through Word Association Test

    ERIC Educational Resources Information Center

    Yücel, Elif Özata; Özkan, Mulis

    2015-01-01

    In this study, we determined cognitive structures and misconceptions about basic ecological concepts by using "word association" tests on secondary school students, age between 12-14 years. Eighty-nine students participated in this study. Before WAT was generated, basic ecological concepts that take place in the secondary science…

  5. Innate immune responses of porcine macrophage cell line (Cdelts2+) to virus-associated virulence determinants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this study was to define the changes in the expression of immune genes in response to virus-associated virulence determinants. We stimulated a monocyte-derived porcine macrophage cell line (Cdelta2+) for 3 and 24h with Imiquimod, Poly IC and Poly IC with Lyovec. Cell lysates were process...

  6. Determination of Lakeshore Technical Institute Associate Degree Nursing Graduates' Nursing Competencies Level.

    ERIC Educational Resources Information Center

    Schrader, Marvin A.

    In an effort to determine the effectiveness of Lakeshore Technical Institute's (LTI's) Associate Degree Nursing (ADN) program, questionnaires were administered to 1982 program graduates (N=45) and their employers (N=43) requesting an assessment of the graduates' preparedness to perform 39 nursing functions. Responses were submitted to a…

  7. A Study to Determine the Perceptions of Vocational Educators Regarding a Professional Association.

    ERIC Educational Resources Information Center

    Gilgannon, Nancy Green

    The study examined selected perceptions and attitudes of randomly identified members of the American Vocational Association (AVA) regarding some of the goals and objectives of this organization. The sample was assessed to determine the relationships among isolated variables (collective bargaining, State legislation, Federal legislation,…

  8. Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study

    SciTech Connect

    Kaplan, M.M.; Boice, J.D. Jr.; Ames, D.B.; Rosenstein, M.

    1988-02-01

    The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease.

  9. Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir.

    PubMed

    Masiá, Mar; Padilla, Sergio; Robledano, Catalina; López, Natividad; Ramos, José Manuel; Gutiérrez, Felix

    2012-03-01

    Initiation of combined antiretroviral therapy (cART) is associated with bone loss, which may be more intense with regimens including tenofovir. The underlying mechanisms are not well understood. Cross-sectional data have linked tenofovir with higher parathyroid hormone (PTH) concentrations in patients with vitamin D deficiency. We performed a longitudinal study with a 48-week follow-up to evaluate sequential changes in PTH and 25-hydroxyvitamin D [25(OH)D] levels in patients starting cART with either tenofovir/emtricitabine or abacavir/lamivudine. Fifty-seven patients were included, 31 initiating tenofovir/emtricitabine and 26 initiating abacavir/lamivudine. Median PTH levels turned out to be significantly higher among tenofovir/emtricitabine users at week 4 (p=0.01), week 24 (p=0.008), and week 36 (p=0.02), and were above the upper limits of normal values (ULN) at weeks 24, 36, and 48 only in patients receiving tenofovir/emtricitabine. 25(OH)D, serum and urine calcium and phosphate, and renal-tubular maximum reabsorption of phosphate to the glomerular filtration rate (TmP/GFR) levels did not differ between the two treatment arms over the study period. Among tenofovir/emtricitabine users, median (interquartile range) PTH concentrations were significantly higher in patients with suboptimal 25(OH)D levels (<30 μg/liter) at week 24 [63 (57.8-82.4) ng/liter vs. 54.3 (34.4-63.067.5) ng/liter, p=0.05] and week 48 [67.5 (59.6-86.0) ng/liter vs. 41.9 (37.3-68.8) ng/liter, p=0.03]. A multivariable logistic regression model showed that tenofovir/emtricitabine use was an independent predictor of high PTH levels (≥53 ng/liter). Starting cART with tenofovir regimens is associated with an elevation in PTH plasma concentrations soon after introducing the drug. Suboptimal baseline 25(OH)D levels increase the risk of developing secondary hyperparathyroidism among tenofovir users. PMID:21639815

  10. Systems and processes for identifying features and determining feature associations in groups of documents

    DOEpatents

    Rose, Stuart J.; Cowley, Wendy E.; Crow, Vernon L.

    2016-01-12

    Systems and computer-implemented processes for identification of features and determination of feature associations in a group of documents can involve providing a plurality of keywords identified among the terms of at least some of the documents. A value measure can be calculated for each keyword. High-value keywords are defined as those keywords having value measures that exceed a threshold. For each high-value keyword, term-document associations (TDA) are accessed. The TDA characterize measures of association between each term and at least some documents in the group. A processor quantifies similarities between unique pairs of high-value keywords based on the TDA for each respective high-value keyword and generates a similarity matrix that indicates one or more sets that each comprise highly associated high-value keywords.

  11. Methylene blue and parathyroid adenoma localization: Three new cases of a rare cutaneous complication.

    PubMed

    Lieberman, Elliot D; Thambi, Rakhi; Pytynia, Kristen B

    2016-02-01

    Methylene blue has been safely used for the localization of parathyroid glands during parathyroidectomy, and only a few adverse effects have been documented. Methylene blue administration as a cause of pulse-oximetry-related skin injury is extremely rare. We describe 2 such cases in patients who developed a blister on the second digit at the pulse oximetry site after an uncomplicated excision of a parathyroid adenoma. In another case, a patient became bradycardic intraoperatively; she was successfully resuscitated, but she incurred a second-degree burn at the pulse oximetry site. In all 3 cases, the burns resolved with local wound care. We publish this report to alert surgeons and anesthesiologists to the risk of skin complications with the use of high-dose intraoperative methylene blue. PMID:26930332

  12. Parathyroid scintigraphy in renal hyperparathyroidism: the added diagnostic value of SPECT and SPECT/CT.

    PubMed

    Taïeb, David; Ureña-Torres, Pablo; Zanotti-Fregonara, Paolo; Rubello, Domenico; Ferretti, Alice; Henter, Ioline; Henry, Jean-François; Schiavi, Francesca; Opocher, Giuseppe; Blickman, Johan G; Colletti, Patrick M; Hindié, Elif

    2013-08-01

    Secondary hyperparathyroidism (sHPT) is a major complication for patients with end-stage renal disease on long-term hemodialysis or peritoneal dialysis. When the disease is resistant to medical treatment, patients with severe sHPT are typically referred for parathyroidectomy (PTx), which usually improves biological parameters as well as clinical signs and symptoms. Unfortunately, early surgical failure with persistent disease may occur in 5%-10% of patients and recurrence reaches 20%-30% at 5 years. Presently, the use of parathyroid scintigraphy in sHPT is usually limited to the management of surgical failures after initial PTx. This review describes the strengths and limitations of typical (99m)Tc-sestamibi imaging protocols, and highlights the potential benefits of using parathyroid scintigraphy in the initial workup of surgical patients. PMID:23751837

  13. [The role of calcium, calcitriol and their receptors in parathyroid regulation].

    PubMed

    Carrillo-López, N; Fernández-Martín, J L; Cannata-Andía, J B

    2009-01-01

    The mechanism of regulation of Parathyroid hormone (PTH) is complex, and diverse factors are involved: the fundamental ones are calcium, calcitriol and phosphorus. Calcium and calcitriol's mechanism of action takes place through its specific receptors, the calcium-sensing receptor (CaR) and the Vitamin D Receptor (VDR). These two factors have an effect not only on its specific receptors, but also they can modify the other receptor in a positive manner, promoting its actions and demonstrating a cooperative effect between the two. Along with calcium and calcitriol, drugs used in the treatment of Chronic Kidney Disease Mineral Bone Disorders (CKD-MBD) also act directly or indirectly on CaR and VDR and therefore are also responsible for the regulation of the parathyroid gland. PMID:19396314

  14. Time series prediction of plasma hormone concentration. Evidence for differences in predictability of parathyroid hormone secretion between osteoporotic patients and normal controls.

    PubMed Central

    Prank, K; Nowlan, S J; Harms, H M; Kloppstech, M; Brabant, G; Hesch, R D; Sejnowski, T J

    1995-01-01

    Recent evidence links osteoporosis, a disease of bone remodeling, to changes in the dynamics of parathyroid hormone secretion. We use nonlinear and linear time series prediction to characterize the secretory dynamics of parathyroid hormone in both healthy human subjects and patients with osteoporosis. Osteoporotic patients appear to lack the periods of high predictability found in normal humans. Our results may provide an explanation for why an intermittent administration of parathyroid hormone is effective in restoring bone mass in osteoporotic patients. Images PMID:7769133

  15. Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.

    PubMed Central

    Naveh-Many, T; Silver, J

    1990-01-01

    In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. Images PMID:2212016

  16. High cervical intravagal hypercellular parathyroid gland as the etiology of severe persistent primary hyperparathyroidism.

    PubMed

    Buell, J F; Fraker, D L; Doppman, J L; Shawker, T H; Skarulis, M C; Spiegel, A M; Marx, S J; Alexander, H R

    1995-11-01

    The preoperative localization and operative management of a high cervical intravagal parathyroid adenoma in a young woman with severe persistent primary hyperparathyroidism is presented. The etiology of persistent hyperparathyroidism is most frequently a missed adenoma that is often in an ectopic location; of these, undescended adenomas represent a small but important proportion. If clinical suspicion and preoperative localization procedures suggest an undescended gland, a direct surgical approach using a high cervical incision and a unilateral exploration is often successful. PMID:7486421

  17. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  18. Association Between Cardiorespiratory Fitness and the Determinants of Glycemic Control Across the Entire Glucose Tolerance Continuum

    PubMed Central

    Malin, Steven K.; Karstoft, Kristian; Knudsen, Sine H.; Haus, Jacob M.; Laye, Matthew J.; Kirwan, John P.

    2015-01-01

    OBJECTIVE Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum. RESEARCH DESIGN AND METHODS A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined. RESULTS A low VO2max was associated with high HbA1c (r = −0.33), high fasting glucose (r = −0.34), high 2-h OGTT glucose (r = −0.33), low SiOGTT (r = 0.73), and high early-phase (r = −0.34) and late-phase (r = −0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum. CONCLUSIONS The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes. PMID:25784661

  19. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    SciTech Connect

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.

  20. Regression of orbital brown tumor after surgical removal of parathyroid adenoma.

    PubMed

    Oliveira, Felipe Martins de; Makimoto, Tiago Eidy; Scalissi, Nilza Maria; Marone, Marília Martins Silveira; Maeda, Sergio Setsuo

    2015-10-01

    Brown tumors are rare skeletal manifestations that occur in less than 2% of primary hyperparathyroidism (PHPT) cases. Even rarer is the occurrence of brown tumor of the orbit, and few cases have been reported around the world. The rare instance of this benign tumor has prompted us to report the case and treatment of an orbital brown tumor in a patient with PHPT caused by parathyroid adenoma. We present the case of a patient undergoing follow-up at a referral center. The 60-year-old female patient, presented herself with progressive swelling in the nasal region, epistaxis and proptosis, she had noticed seven months prior to our examination. Multiple imaging and laboratory findings revealed parathyroid hormone (PTH)-dependent hypercalcemia (total calcium = 14.3 mg/dL and PTH = 1,573 pg/mL), a nodular lesion in the upper pole of the left thyroid lobe and increased uptake in left upper cervical region. The patient underwent left superior parathyroidectomy in September 2011, which led to the normalization of hypercalcemia and regression of the orbital tumor, as seen on control CT scan. This case highlights the spontaneous regression of the brown tumor after surgical management of the parathyroid adenoma. PMID:26331231

  1. Surgical treatment of primary hyperparathyroidism due to parathyroid tumor: A 15-year experience

    PubMed Central

    Feng, Lu; Zhang, Xu; Liu, Shan-Ting

    2016-01-01

    The aim of this study was to highlight our experience over a 15-year period in dealing with primary hyperparathyroidism (PHPT) due to a parathyroid tumor. Parathyroidectomy is the standard therapy for patients with PHPT. Our study included all patients with PHPT treated by parathyroidectomy at the Affiliated Cancer Hospital of Zhengzhou University, China. Between 1998 and 2013, a total of 107 patients were recruited. Their clinical data, presentation, laboratory examinations, imageological diagnoses and surgical approaches were analyzed retrospectively. Eighty-four cases (78.5%) were followed up. During a median follow-up period of 5.7 years, a total of 80 patients were without recurrence and metastasis. The main symptoms of PHPT patients were palpable neck mass, joint pains and pathological fracture. The high levels of preoperative parathyroid hormone (PTH) and serum calcium in PHPT patients decreased to below the normal upper limit within 3 days of surgery. The sensitivity of neck ultrasonography, sestamibi scanning, CT, MRI and the combination of three or four types of test were 86.0%, 90.4%, 80.8%, 79.6% and 96.1%, respectively. A 50% or greater drop in PTH levels within 20 min compared with the highest PTH levels before surgery occurred in 95/107 cases (88.8%). Transient hypocalcemia was the most common surgical complication. The ultrasonography and sestamibi scan is the most effective examination for parathyroid tumor. The 20 min PTH measurement appears to be extremely useful, and avoids unnecessary bilateral exploration. PMID:27602126

  2. Adult rheumatoid arthritis is associated with MC1, a new HLA-D encoded determinant.

    PubMed

    Carpenter, A B; Kahl, L E; Bartkowiak, C D; Duquesnoy, R J; Eisenbeis, C H

    1988-03-01

    We evaluated the association of a new HLA-D encoded determinant, MC1, with adult rheumatoid arthritis (RA). This determinant associates with DR1 and DR4 and can be defined by serological typing. We found MC1 in 83% of 80 patients with RA vs 43% of controls. Although the frequencies of DR1 and DR4 were both significantly increased in patients with RA compared with controls, MC1 had the highest relative risk (6.2) of any HLA-DR antigen tested. MC1 negative and positive populations were not significantly different in any of a variety of clinical and laboratory variables including age, sex, disease duration, age at onset, hours of morning stiffness, functional class, joint count, presence of subcutaneous nodules or bony erosions, frequency of side effects to gold or D-penicillamine, sedimentation rate, and antinuclear antibody. PMID:2454315

  3. Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

    PubMed Central

    Kroll, Martin H.; Bi, Caixia; Garber, Carl C.; Kaufman, Harvey W.; Liu, Dungang; Caston-Balderrama, Anne; Zhang, Ke; Clarke, Nigel; Xie, Minge; Reitz, Richard E.; Suffin, Stephen C.; Holick, Michael F.

    2015-01-01

    Background Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season. Objective Characterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels. Method We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL). Findings Seasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2. Interpretation 25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for

  4. The Efficacy of Parathyroid Hormone Analogues in Combination With Bisphosphonates for the Treatment of Osteoporosis

    PubMed Central

    Li, Wan; Chen, Wenjian; Lin, Yang

    2015-01-01

    Abstract Parathyroid hormone (PTH) analogues increase bone strength primarily by stimulating bone formation, whereas antiresorptive drugs (bisphosphonates) reduce bone resorption. Therefore, some studies have been designed to test the hypothesis that the concurrent administration of the 2 agents would increase bone density more than the use of either one alone. This meta-analysis aimed to determine whether combining PTH analogues with bisphosphonates would be superior to PTH alone. Electronic databases were searched to identify relevant publications up to March, 2014. Randomized controlled trials (RCTs) comparing PTH analogues combined bisphosphonates with PTH for osteoporosis were analyzed. According to the Cochrane Handbook for systematic Reviews of Interventions 5.2, we identified eligible studies, evaluated the methodological quality, and abstracted relevant data. Totally 7 studies involving 641 patients were included for meta-analysis. The pooled data showed that there were no significant differences in the percent change of spine BMD (MD1-year = −0.97, 95% CI −2.81 to 0.86, P = 0.30; MD2-year =  − 0.57, 95% CI −5.01 to 6.14, P = 0.84), femoral neck BMD (MD1-year = 0.60, 95% CI −0.91 to 2.10, P = 0.44; MD2-year = −0.73, 95% CI −4.97 to 3.51, P = 0.74), the risk of vertebral fracture (risk ratio [RR] = 1.27; 95% CI 0.29–5.57; P = 0.75), and the risk of nonvertebral fracture (RR = 0.97; 95% CI 0.40–2.35; P = 0.95) between the 2 groups, whereas combination group improves the percent change of hip BMD at 1 year (MD = 1.16, 95% CI 0.56–1.76; P < 0.01) than PTH analogues group. Our results showed that there was no evidence for the superiority of combination therapy, although significant change was found for hip BMD at 1 year in combination group. Further large multicenter randomized controlled trials are still needed to investigate the efficacy of combination therapy. PMID:26402797

  5. A Method for and Issues Associated with the Determination of Space Suit Joint Requirements

    NASA Technical Reports Server (NTRS)

    Matty, Jennifer E.; Aitchison, Lindsay

    2010-01-01

    This joint mobility KC lecture included information from two papers, "A Method for and Issues Associated with the Determination of Space Suit Joint Requirements" and "Results and Analysis from Space Suit Joint Torque Testing," as presented for the International Conference on Environmental Systems in 2009 and 2010, respectively. The first paper discusses historical joint torque testing methodologies and approaches that were tested in 2008 and 2009. The second paper discusses the testing that was completed in 2009 and 2010.

  6. Food neophobia in German adolescents: Determinants and association with dietary habits.

    PubMed

    Roßbach, Sarah; Foterek, Kristina; Schmidt, Inga; Hilbig, Annett; Alexy, Ute

    2016-06-01

    Food neophobia (FN) is described as the rejection to eat unknown foods. Because only little is known about the role of FN in adolescence the aim of this study was to examine potential determinants of FN and associations with dietary habits of DONALD study participants. FN was measured with Pliner's and Hobden's Food Neophobia Scale (FN Score (FNS): range 10-70) in 166 10-18-year-old adolescents. Participants' age, sex, body weight status and duration of breast-feeding as well as parents' FN and educational status were considered as determinants. Energy intake, distribution of macronutrients and two variety scores were calculated from 3-day weighed dietary records. Multivariable general linear models were performed for data analyses. Boys and girls did not differ in their FNS (median (Min-Max): boys 31 (10-58), girls 32 (14-59)). Increasing age (p = 0.010) and duration of total breast-feeding (p = 0.006) were associated with decreasing FNS in girls only. FN was further positively associated with parental FN in the total sample (p = 0.004). FN was negatively associated with protein intake in the total sample (p = 0.017). The overall low level of FN in the DONALD study can be ascribed to the low level of FN in adolescence in general. Congruently with other studies, age and breast-feeding duration were identified as determinants of girls' FN and parental FN was identified as determinant of FN in the total sample. Further, our results indicate that FN leads to reduced protein intakes. Dietary variety was not strongly affected, possibly because of a broad variety of food supply in Germany. PMID:26928790

  7. Gas chromatographic analysis of petroleum associated condensate oil with simultaneous determination of some characteristic physical parameters.

    PubMed

    Moustafa, N E

    2008-01-01

    A method is developed for the analysis of associated condensate by capillary gas chromatography (GC) with simultaneous determination of its major physical characteristic parameters. The method aims at the qualitative and quantitative determination of C(2)-C(36) alkanes, methylcyclopentane, cyclohexane, methylcyclohexane, benzene, toluene, ethylbenzene, xylenes, and 1,2,4-trimethylbenzene. This composition is according to the petroleum companies demand. The method is used for the simultaneous determination of the condensate average molecular weight, density, carbon-to-hydrogen ratio, and boiling range. The data obtained by the method has a good agreement with those obtained by other methods. The literature methods cited later used a simulated distillation method to obtain the hydrocarbon distribution spectrum of the given condensate sample. The obtained results revealed that the GC capillary method used is most rapid and accurate for achieving the demanded analytical report. PMID:18492346

  8. A case report on acute severe hyponatraemia following parathyroid surgery for primary hyperparathyroidism—A rare but life threatening complication

    PubMed Central

    Hillary, S.L.; Hemead, H.; Berthoud, M.; Balasubramanian, S.P.

    2016-01-01

    Introduction Parathyroidectomy is a common operation, which is well tolerated and associated with low morbidity. Patients are usually discharged within 24 hours of surgery. Severe postoperative hyponatraemia is a rare complication which can cause significant morbidity including seizure, coma, respiratory arrest and even death. Presentation of case We present two patients with clinically significant hyponatremia resulting in seizures and collapse within 24 hours after parathyroidectomy, an unreported complication following surgery for primary hyperparathyroidism. One patient required support on the High Dependency Unit and both were treated with fluid restriction which resulted in correction of their electrolyte balance. Discussion We believe this was caused by the relative inability to secrete a water load after surgery and non-psychogenic polydipsia. Preoperatively, neither patient was prescribed any routine medications nor did they have any risk factors for hyponatremia. Both had normal preoperative sodium levels. It is usual practice is to advise patients to increase oral water intake when they are hypercalcaemic. The aim of parathyroidectomy is to treat hypercalcaemia by stopping excess PTH secretion from abnormal parathyroid glands. These patients continued to follow this advice after surgery when they were eucalcaemic after their operation and because they were thirsty. The patients drank several litres of water in 12–24 hours after surgery. We believe that this may have contributed to this complication. Conclusion Healthcare professionals need to be aware of this complication and patients should be advised to restrict intake of free water after surgery. PMID:26994458

  9. Functional analysis of 'a' determinant mutations associated with occult HBV in HIV-positive South Africans.

    PubMed

    Powell, Eleanor A; Boyce, Ceejay L; Gededzha, Maemu P; Selabe, Selokela G; Mphahlele, M Jeffrey; Blackard, Jason T

    2016-07-01

    Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with the development of hepatocellular carcinoma, reactivation during immune suppression, and virus transmission. Viral mutations contribute significantly to the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of particular interest, as these mutations are associated with immune escape, vaccine escape and diagnostic failure. We examined the effects of selected occult HBV-associated mutations identified in a population of HIV-positive South Africans on HBsAg production in vitro. Mutations were inserted into two different chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg levels were quantified by enzyme-linked immunosorbent assay (ELISA), while the detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y) resulted in decreased HBsAg expression in one viral background but not in the second viral background. One mutation (N146D) led to a decrease in HBsAg detected as compared to HA-tag, indicating that this mutation compromises the ability of the ELISA to detect HBsAg. The contribution of occult-associated mutations to the HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing the effect of the mutation in a single viral background, and rigorous analysis of these mutations is required. PMID:27031988

  10. Plasma Parathyroid Hormone Is Independently Related to Nocturnal Blood Pressure in Hypertensive Patients: The Styrian Hypertension Study.

    PubMed

    Verheyen, Nicolas D; Kienreich, Katharina; Gaksch, Martin; van Ballegooijen, Adriana J; Grübler, Martin R; Hartaigh, Briain Ó; Schmid, Johannes; Fahrleitner-Pammer, Astrid; Kraigher-Krainer, Elisabeth; Colantonio, Caterina; Belyavskiy, Evgeny; Treiber, Gerlies; Catena, Cristiana; Brussee, Helmut; Pieske, Burkert; März, Winfried; Tomaschitz, Andreas; Pilz, Stefan

    2016-06-01

    High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24-hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross-sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39-61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH-modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β-coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies. PMID:26456544

  11. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2.

    PubMed

    Johnston, Christopher A; Kimple, Adam J; Giguère, Patrick M; Siderovski, David P

    2008-07-01

    A critical role of the Gbetagamma dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Galpha subunit by cell-surface G-protein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gbetagamma dimer has not previously been available. Here, we describe the structural determinants of Gbeta1gamma2 in complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as obtained by X-ray crystallography. The structure reveals that several critical residues within PTH1R contact only Gbeta residues located within the outer edge of WD1- and WD7-repeat segments of the Gbeta toroid structure. These regions encompass a predicted membrane-facing region of Gbeta thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gbeta1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gbeta1gamma2 activation of the effector phospholipase-C beta. PMID:18611381

  12. Overexpression of the Transcriptional Factor Runx2 in Osteoblasts Abolishes the Anabolic Effect of Parathyroid Hormone in Vivo

    PubMed Central

    Merciris, Didier; Marty, Caroline; Collet, Corinne; de Vernejoul, Marie-Christine; Geoffroy, Valerie

    2007-01-01

    There is convincing evidence that Runx2 could be a regulator of the anabolic action of parathyroid hormone (PTH) in bone. We therefore decided to determine how Runx2 overexpression in osteoblasts affects the anabolic response to PTH. Transgenic osteoporotic female mice overexpressing Runx2 (TG) and their wild-type littermates (WT) were treated with PTH (100 μg/kg/day, 7 days a week) or with the vehicle for 6 weeks. Unexpectedly, Runx2 overexpression blunted the increase in the mineral density and volume of bone induced by intermittent PTH in WT mice. Our findings also indicate that PTH failed to increase bone formation in TG mice overexpressing Runx2. This abolition of the effect of PTH by Runx2 overexpression was attributable to a decrease in the differentiation of osteoblastic cells both in vivo and in vitro. Finally, we showed that less cAMP was induced by PTH and that there were fewer PTH binding sites in TG than WT osteoblasts. In conclusion, our findings demonstrate that in vivo a high level of Runx2 abolishes the anabolic effect of PTH, probably via a decrease in the sensitivity of TG osteoblasts to PTH, and that the level of expression of Runx2 is critical if PTH is to produce its anabolic effect on bone in vivo. PMID:17456773

  13. Multiple biomarker strategy based on parathyroid hormone and natriuretic peptides testing for improved prognosis of chronic heart failure.

    PubMed

    Gruson, Damien; Ahn, Sylvie A; Rousseau, Michel F

    2015-02-01

    Biomarkers offer new perspectives for a more personalized management of patients with heart failure (HF). Hyperparathyroidism is common in HF patients and parathyroid hormone (PTH) testing might provide added value for the prognostication of HF patients. Our objectives were therefore to determine the efficiency of multiple biomarker strategy based on PTH and natriuretic peptides measurement for the risk stratification of patients with HF. Circulating concentrations of bioactive PTH 1-84 and natriuretic peptides, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), were measured with automated immunoassays in 45 healthy individuals and 137 HF patients with reduced left ventricular ejection fraction. Circulating levels of PTH 1-84 and natriuretic peptides were significantly increased in HF patients in comparison to HF patients. Over a long-term follow-up, baseline PTH 1-84 levels were related to the risk of cardiovascular death. Furthermore, in multiple biomarker approach, PTH measurement was additive to BNP and NT-proBNP testing for the cardiovascular risk assessment of HF patients. In conclusion, the combination of PTH 1-84 and natriuretic peptides testing improves the prognostication of HF patients and might allowed more personalized approach for risk stratification and treatment selection in HF patients. PMID:25572303

  14. The Burden and Determinants of Neck Pain in Whiplash-Associated Disorders After Traffic Collisions

    PubMed Central

    Carroll, Linda J.; Cassidy, J. David; Hogg-Johnson, Sheilah; Côté, Pierre; Guzman, Jamie; Peloso, Paul; Nordin, Margareta; Hurwitz, Eric; van der Velde, Gabrielle; Carragee, Eugene; Haldeman, Scott

    2008-01-01

    Study Design Best evidence synthesis. Objective To undertake a best evidence synthesis on the burden and determinants of whiplash-associated disorders (WAD) after traffic collisions. Study Design Summary of Background Data. Previous best evidence synthesis on WAD has noted a lack of evidence regarding incidence of and risk factors for WAD. Therefore there was a warrant of a reanalyze of this body of research. Methods A systematic search of Medline was conducted. The reviewers looked for studies on neck pain and its associated disorders published 1980 –2006. Each relevant study was independently and critically reviewed by rotating pairs of reviewers. Data from studies judged to have acceptable internal validity (scientifically admissible) were abstracted into evidence tables, and provide the body of the best evidence synthesis. Results The authors found 32 scientifically admissible studies related to the burden and determinants of WAD. In the Western world, visits to emergency rooms due to WAD have increased over the past 30 years. The annual cumulative incidence of WAD differed substantially between countries. They found that occupant seat position and collision impact direction were associated with WAD in one study. Eliminating insurance payments for pain and suffering were associated with a lower incidence of WAD injury claims in one study. Younger ages and being a female were both associated with filing claims or seeking care for WAD, although the evidence is not consistent. Preliminary evidence suggested that headrests/car seats, aimed to limiting head extension during rear-end collisions had a preventive effect on reporting WAD, especially in females. Conclusion WAD after traffic collisions affects many people. Despite many years of research, the evidence regarding risk factors for WAD is sparse but seems to include personal, societal, and environmental factors. More research including, well-defined studies with accurate denominators for calculating risk

  15. Association of substance-use behaviours and their social-cognitive determinants in secondary school students.

    PubMed

    Victoir, An; Eertmans, Audrey; Van den Bergh, Omer; Van den Broucke, Stephan

    2007-02-01

    In two samples of Flemish secondary school students, co-occurrence of different types of substance use was observed: smoking was associated with marijuana use in Sample 1 (n = 597) and alcohol consumption in Sample 2 (n = 403). It was investigated whether social-cognitive determinants of these behaviours were also associated. Low to medium correlations were observed. Confirmatory factor analyses showed that a model with general social-cognitive factors (across different substances) did not have adequate fit. Substance use was mainly associated with variables referring to the specific substance under consideration, with the exception of self-efficacy in buying and smoking cigarettes; this factor was linked not only to smoking but also to alcohol and marijuana use. Adolescents who regularly used two substances generally held positions on social-cognitive scales that were more unfavourable than those who only used one substance. In order to change determinants of use, substance-specific cognitions and skills may be important targets. PMID:16807377

  16. Tobacco consumption and illegal drug use among Bangladeshi males: association and determinants.

    PubMed

    Kabir, M A; Goh, Kim-Leng; Khan, M M H

    2013-03-01

    This article aimed to identify the determinants of tobacco consumption and illegal drug use (IDU) as well as to examine the association between these two variables using a representative sample of 3,771 Bangladeshi males aged 15 to 54 years. Data were collected through Bangladesh Demographic and Health Survey 2007. To identify the determinants, the patterns of tobacco consumption and IDU were analyzed by age, education and occupation, residence, mass media, premarital sex, wealth, and sexually transmitted infections (STIs). Prevalence of smoking cigarette and bidi was roughly 60%. However, the prevalence of IDU was 3.4%, and this proportion is statistically significant (Z = 11.32, p = .000). After bivariate analysis, almost all variables except STIs were significantly associated with tobacco consumption. Similarly, all variables except residence and mass media were associated with IDU. Based on multivariable adjusted logistic regression analysis, the likelihood of using IDU was approximately twofold (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.23-2.53) among bidi smokers and fourfold (OR = 3.8, 95% CI = 2.62-5.56) among cigarette smokers as compared with nonsmokers. PMID:23065136

  17. Identification of a Novel Determinant for Membrane Association in Hepatitis C Virus Nonstructural Protein 4B▿

    PubMed Central

    Gouttenoire, Jérôme; Castet, Valérie; Montserret, Roland; Arora, Naveen; Raussens, Vincent; Ruysschaert, Jean-Marie; Diesis, Eric; Blum, Hubert E.; Penin, François; Moradpour, Darius

    2009-01-01

    Nonstructural protein 4B (NS4B) plays an essential role in the formation of the hepatitis C virus (HCV) replication complex. It is a relatively poorly characterized integral membrane protein predicted to comprise four transmembrane segments in its central portion. Here, we describe a novel determinant for membrane association represented by amino acids (aa) 40 to 69 in the N-terminal portion of NS4B. This segment was sufficient to target and tightly anchor the green fluorescent protein to cellular membranes, as assessed by fluorescence microscopy as well as membrane extraction and flotation analyses. Circular dichroism and nuclear magnetic resonance structural analyses showed that this segment comprises an amphipathic α-helix extending from aa 42 to 66. Attenuated total reflection infrared spectroscopy and glycosylation acceptor site tagging revealed that this amphipathic α-helix has the potential to traverse the phospholipid bilayer as a transmembrane segment, likely upon oligomerization. Alanine substitution of the fully conserved aromatic residues on the hydrophobic helix side abrogated membrane association of the segment comprising aa 40 to 69 and disrupted the formation of a functional replication complex. These results provide the first atomic resolution structure of an essential membrane-associated determinant of HCV NS4B. PMID:19357161

  18. Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid and aorta of uremic rats

    PubMed Central

    Ritter, Cynthia S.; Zhang, Sarah; Delmez, James; Finch, Jane L; Slatopolsky, Eduardo

    2015-01-01

    Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined. The effect of vitamin D receptor activator therapy in CKD on expression of Klotho in various tissues is also in debate. In uremic rats (surgical 5/6th nephrectomy model), we compared 3-months of treatment with and without paricalcitol on Klotho immunostaining in the kidney, parathyroid glands and aorta. With uremia, Klotho was unchanged in the parathyroid, significantly decreased in the kidney (66%) and the intimal-medial area of the aorta (69%), and significantly increased in the adventitial area of the aorta (67%) compared with controls. Paricalcitol prevented the decrease in Klotho in the kidney, increased expression in the parathyroid (31%), had no effect in the aortic media, but blunted the increase of Klotho in aortic adventitia. We propose that fibroblasts are responsible for expression of Klotho in the adventitia. In hyperplastic human parathyroid tissue from uremic patients, Klotho was higher in oxyphil compared with chief cells. Thus, under our conditions of moderate CKD and mild-to-moderate hyperphosphatemia in rats, the differential expression of Klotho and its regulation by paricalcitol in uremia is tissue-dependent. PMID:25692955

  19. Discomfort associated with fixed orthodontic appliances: determinant factors and influence on quality of life

    PubMed Central

    Marques, Leandro Silva; Paiva, Saul Martins; Vieira-Andrade, Raquel Gonçalves; Pereira, Luciano José; Ramos-Jorge, Maria Letícia

    2014-01-01

    Objective To investigate the determinant factors of discomfort attributed to the use of fixed orthodontic appliance and the effect on the quality of life of adolescents. Material and Methods Two hundred and seventy-two individuals aged between 9 and 18 years old, enrolled in public and private schools and undergoing orthodontic treatment with fixed appliance participated in this cross-sectional study. The participants were randomly selected from a sample comprising 62,496 individuals of the same age group. Data was collected by means of questionnaires and an interview. Discomfort intensity and bio-psychosocial variables were assessed using the Oral Impact on Daily Performance questionnaire. Self-esteem was determined using the Global Negative Self-Evaluation questionnaire. Statistical analysis involved the chi-square test and both simple and multiple Poisson regression analyses. Results Although most individuals did not present discomfort, there was a prevalence of 15.9% of impact on individuals' daily life exclusively due to the use of fixed orthodontic appliance . Age [PR: 3.2 (95% CI: 1.2-8.5)], speech impairment [PR: 2.2 (95% CI: 1.1-4.6)], poor oral hygiene [PR: 2.4 (95% CI: 1.2-4.8)] and tooth mobility [PR: 3.9 (95% CI: 1.8-8.1)] remained independently associated with a greater prevalence of discomfort (P ≤ 0.05). Conclusions Discomfort associated with the use of fixed orthodontic appliances exerted a negative influence on the quality of life of the adolescents comprising the present study. The determinants of this association were age, poor oral hygiene, speech impairment and tooth mobility. PMID:25162573

  20. A Co-Association Network Analysis of the Genetic Determination of Pig Conformation, Growth and Fatness

    PubMed Central

    Puig-Oliveras, Anna; Ballester, Maria; Corominas, Jordi; Revilla, Manuel; Estellé, Jordi; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Folch, Josep M.

    2014-01-01

    Background Several QTLs have been identified for major economically relevant traits in livestock, such as growth and meat quality, revealing the complex genetic architecture of these traits. The use of network approaches considering the interactions of multiple molecules and traits provides useful insights into the molecular underpinnings of complex traits. Here, a network based methodology, named Association Weight Matrix, was applied to study gene interactions and pathways affecting pig conformation, growth and fatness traits. Results The co-association network analysis underpinned three transcription factors, PPARγ, ELF1, and PRDM16 involved in mesoderm tissue differentiation. Fifty-four genes in the network belonged to growth-related ontologies and 46 of them were common with a similar study for growth in cattle supporting our results. The functional analysis uncovered the lipid metabolism and the corticotrophin and gonadotrophin release hormone pathways among the most important pathways influencing these traits. Our results suggest that the genes and pathways here identified are important determining either the total body weight of the animal and the fat content. For instance, a switch in the mesoderm tissue differentiation may determinate the age-related preferred pathways being in the puberty stage those related with the miogenic and osteogenic lineages; on the contrary, in the maturity stage cells may be more prone to the adipocyte fate. Hence, our results demonstrate that an integrative genomic co-association analysis is a powerful approach for identifying new connections and interactions among genes. Conclusions This work provides insights about pathways and key regulators which may be important determining the animal growth, conformation and body proportions and fatness traits. Molecular information concerning genes and pathways here described may be crucial for the improvement of genetic breeding programs applied to pork meat production. PMID:25503799

  1. Metagenome-Wide Association of Microbial Determinants of Host Phenotype in Drosophila melanogaster

    PubMed Central

    Newell, Peter D.; Douglas, Angela E.

    2014-01-01

    ABSTRACT Animal-associated bacteria (microbiota) affect host behaviors and physiological traits. To identify bacterial genetic determinants of microbiota-responsive host traits, we employed a metagenome-wide association (MGWA) approach in two steps. First, we measured two microbiota-responsive host traits, development time and triglyceride (TAG) content, in Drosophila melanogaster flies monoassociated with each of 41 bacterial strains. The effects of monoassociation on host traits were not confined to particular taxonomic groups. Second, we clustered protein-coding sequences of the bacteria by sequence similarity de novo and statistically associated the magnitude of the host trait with the bacterial gene contents. The animals had been monoassociated with genome-sequenced bacteria, so the metagenome content was unambiguous. This analysis showed significant effects of pyrroloquinoline quinone biosynthesis genes on development time, confirming the results of a published transposon mutagenesis screen, thereby validating the MGWA; it also identified multiple genes predicted to affect host TAG content, including extracellular glucose oxidation pathway components. To test the validity of the statistical associations, we expressed candidate genes in a strain that lacks them. Monoassociation with bacteria that ectopically expressed a predicted oxidoreductase or gluconate dehydrogenase conferred reduced Drosophila TAG contents relative to the TAG contents in empty vector controls. Consistent with the prediction that glucose oxidation pathway gene expression increased bacterial glucose utilization, the glucose content of the host diet was reduced when flies were exposed to these strains. Our findings indicate that microbiota affect host nutritional status through modulation of nutrient acquisition. Together, these findings demonstrate the utility of MGWA for identifying bacterial determinants of host traits and provide mechanistic insight into how gut microbiota modulate the

  2. A Review of Hypothesized Determinants Associated with Bighorn Sheep (Ovis canadensis) Die-Offs

    PubMed Central

    Miller, David S.; Hoberg, Eric; Weiser, Glen; Aune, Keith; Atkinson, Mark; Kimberling, Cleon

    2012-01-01

    Multiple determinants have been hypothesized to cause or favor disease outbreaks among free-ranging bighorn sheep (Ovis canadensis) populations. This paper considered direct and indirect causes of mortality, as well as potential interactions among proposed environmental, host, and agent determinants of disease. A clear, invariant relationship between a single agent and field outbreaks has not yet been documented, in part due to methodological limitations and practical challenges associated with developing rigorous study designs. Therefore, although there is a need to develop predictive models for outbreaks and validated mitigation strategies, uncertainty remains as to whether outbreaks are due to endemic or recently introduced agents. Consequently, absence of established and universal explanations for outbreaks contributes to conflict among wildlife and livestock stakeholders over land use and management practices. This example illustrates the challenge of developing comprehensive models for understanding and managing wildlife diseases in complex biological and sociological environments. PMID:22567546

  3. Plasmid-borne cadmium resistant determinants are associated with the susceptibility of Listeria monocytogenes to bacteriophage.

    PubMed

    Zhang, Hui; Zhou, Yan; Bao, Hongduo; Zhang, Lili; Wang, Ran; Zhou, Xiaohui

    2015-03-01

    Listeria monocytogenes is an intracellular pathogen causing gastroenteritis, central nervous system infections and abortions. Chromosomal virulence determinants have been extensively investigated. However, the function of genes encoded by plasmids in L. monocytogenes has not been fully understood. In this study, we determined the prevalence and molecular profile of plasmids in food isolates of L. monocytogenes and examined the contribution of four plasmid-borne cadmium-resistant genes to the susceptibility of L. monocytogenes to bacteriophage infection. The results showed that plasmids were isolated from 55% (11/20) of the isolates and the plasmids exhibited 10 molecular types as determined by restriction enzyme digestion. Furthermore, 65% and 15% of the isolates were tolerant to cadmium and benzalkonium chloride (BC), respectively. All the BC-resistant isolates were resistant to cadmium. The prevalence of predicted cadmium resistance determinants (cadA1, cadA2, cadA3 and cadC) was determined and the results showed that cadA1 (35%) in isolates of serotypes 1/2a and 1/2b was much more prevalent than cadC (15%). As expected, both cadA and cadC mutants had reduced resistance to cadmium, while the resistance to BC was not significantly affected. Interestingly, both cadA and cadC mutants showed significantly higher susceptibility against L. monocytogenes phage LipG2-5 and FWLLm3 compared with the wide-type strain. Based on these results, we concluded that plasmids from L. monocytogenes encoded important functional determinants that are not only associated with cadmium resistance, but also phage susceptibility. PMID:25721472

  4. TRPV4 associates environmental temperature and sex determination in the American alligator

    PubMed Central

    Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Saito, Shigeru; Lowers, Russell H.; Ogino, Yukiko; Fukuta, Naomi; Katsu, Yoshinao; Ohta, Yasuhiko; Tominaga, Makoto; Guillette Jr, Louis J.; Iguchi, Taisen

    2015-01-01

    Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual’s genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 °C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 °C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism. PMID:26677944

  5. TRPV4 associates environmental temperature and sex determination in the American alligator.

    PubMed

    Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Saito, Shigeru; Lowers, Russell H; Ogino, Yukiko; Fukuta, Naomi; Katsu, Yoshinao; Ohta, Yasuhiko; Tominaga, Makoto; Guillette, Louis J; Iguchi, Taisen

    2015-01-01

    Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual's genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 °C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 °C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism. PMID:26677944

  6. Microcin determinants are associated with B2 phylogroup of human fecal Escherichia coli isolates.

    PubMed

    Micenková, Lenka; Bosák, Juraj; Štaudová, Barbora; Kohoutová, Darina; Čejková, Darina; Woznicová, Vladana; Vrba, Martin; Ševčíková, Alena; Bureš, Jan; Šmajs, David

    2016-06-01

    Escherichia coli strains are classified into four main phylogenetic groups (A, B1, B2, and D) and strains of these phylogroups differ in a number of characteristics. This study tested whether human fecal E. coli isolates belonging to different phylogroups differ in prevalence of bacteriocinogenic isolates and prevalence of individual bacteriocinogenic determinants. A set of 1283 fecal E. coli isolates from patients with different diseases was tested for the presence of DNA regions allowing classification into E. coli phylogroups and for the ability to produce bacteriocins (23 colicins and 7 microcins). Of the isolates tested, the most common was phylogroup B2 (38.3%) followed by phylogroups A (28.3%), D (26.3%) and B1 (7.2%). Altogether, 695 bacteriocin producers were identified representing 54.2% of all tested isolates. The highest prevalence of bacteriocin producers was found in group B2 (60.3%) and the lowest in group B1 (44.6%). Determinants encoding colicins E1, Ia, and microcin mV were most common in phylogroup A, determinants encoding microcins mM and mH47 were most common in phylogroup B2, and determinant encoding mB17 was most common in phylogroup D. The highest prevalence of bacteriocinogeny was found in phylogroup B2, suggesting that bacteriocinogeny and especially the synthesis of microcins was associated with virulent and resident E. coli strains. PMID:26987297

  7. Cervical strain determined by ultrasound elastography and its association with spontaneous preterm delivery

    PubMed Central

    Hernandez-Andrade, Edgar; Romero, Roberto; Korzeniewski, Steven J.; Ahn, Hyunyoung; Aurioles-Garibay, Alma; Garcia, Maynor; Schwartz, Alyse G.; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2014-01-01

    Objective To determine if there is an association between cervical strain, evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD) <37 weeks of gestation. Methods One hundred and eighty nine (189) women at 16–24 weeks of gestation were evaluated. Ultrasound elastography was used to estimate cervical strain in three anatomical planes: one mid-sagittal in the same plane used for cervical length measurement, and two cross sectional images: one at the level of the internal cervical os, and the other at the level of the external cervical os. In each plane, two regions of interest (endocervix and entire cervix) were examined; a total of six regions of interest were evaluated. Results The prevalence of sPTD was 11% (21/189). Strain values from each of the six cervical regions correlated weakly with cervical length (r= −0.24, p<0.001 to r= −0.03, p=0.69). Strain measurements obtained in a cross sectional view of the internal cervical os were significantly associated with sPTD. Women with strain values ≤25th centile in the endocervical canal (0.19) and in the entire cervix (0.14) were 80% less likely to have a sPTD than women with strain values >25th centile (endocervical: odds ratio [OR] 0.2; 95% confidence interval [CI], 0.03–0.96; entire cervix: OR 0.17; 95% CI, 0.03–0.9). Additional adjustment for gestational age, race, smoking status, parity, maternal age, pre-pregnancy body mass index and previous preterm delivery did not appreciably alter the magnitude or statistical significance of these associations. Strain values obtained from the external cervical os and from the sagittal view were not associated with sPTD. Conclusion Low strain values in the internal cervical os were associated with a significantly lower risk of spontaneous preterm delivery <37 weeks of gestation. PMID:24356388

  8. Identification and preservation of the parathyroid gland during total thyroidectomy in dogs with bilateral thyroid carcinoma: a report of six cases

    PubMed Central

    FUKUI, Sho; ENDO, Yoshifumi; HIRAYAMA, Kazuko; TANIYAMA, Hiroyuki; KADOSAWA, Tsuyoshi

    2015-01-01

    Simultaneous removal of bilateral thyroid tumors was performed while preserving the parathyroid gland in six dogs. At least one external parathyroid gland was identified in all dogs. In five cases, the external parathyroid gland and its blood supply were preserved intact. In one dog, the vessels supplying the external parathyroid gland had been invaded by the tumor, and the gland was thus removed and reimplanted into the sternohyoid muscle. That dog required postoperative treatment with oral calcium gluconate and vitamin D3. Local tumor recurrence was not observed in any of the cases. The mean survival time was 920 days. We found that the external parathyroid gland could be identified and preserved in most dogs undergoing total thyroidectomy. PMID:25716481

  9. Squalene synthase, a determinant of Raft-associated cholesterol and modulator of cancer cell proliferation.

    PubMed

    Brusselmans, Koen; Timmermans, Leen; Van de Sande, Tine; Van Veldhoven, Paul P; Guan, Guimin; Shechter, Ishaiahu; Claessens, Frank; Verhoeven, Guido; Swinnen, Johannes V

    2007-06-29

    Several cues for cell proliferation, migration, and survival are transmitted through lipid rafts, membrane microdomains enriched in sphingolipids and cholesterol. Cells obtain cholesterol from the circulation but can also synthesize cholesterol de novo through the mevalonate/isoprenoid pathway. This pathway, however, has several branches and also produces non-sterol isoprenoids. Squalene synthase (SQS) is the enzyme that determines the switch toward sterol biosynthesis. Here we demonstrate that in prostate cancer cells SQS expression is enhanced by androgens, channeling intermediates of the mevalonate/isoprenoid pathway toward cholesterol synthesis. Interestingly, the resulting increase in de novo synthesis of cholesterol mainly affects the cholesterol content of lipid rafts, while leaving non-raft cholesterol levels unaffected. Conversely, RNA interference-mediated SQS inhibition results in a decrease of raft-associated cholesterol. These data show that SQS activity and de novo cholesterol synthesis are determinants of membrane microdomain-associated cholesterol in cancer cells. Remarkably, SQS knock down also attenuates proliferation and induces death of prostate cancer cells. Similar effects are observed when cancer cells are treated with the chemical SQS inhibitor zaragozic acid A. Importantly, although the anti-tumor effect of statins has previously been attributed to inhibition of protein isoprenylation, the present study shows that specific inhibition of the cholesterol biosynthesis branch of the mevalonate/isoprenoid pathway also induces cancer cell death. These findings significantly underscore the importance of de novo cholesterol synthesis for cancer cell biology and suggest that SQS is a potential novel target for antineoplastic intervention. PMID:17483544

  10. Association of Maternal Working Condition with Low Birth Weight: The Social Determinants of Health Approach

    PubMed Central

    Mahmoodi, Z; Karimlou, M; Sajjadi, H; Dejman, M; Vameghi, M; Dolatian, M; Mahmoodi, A

    2015-01-01

    Background: The socioeconomic conditions have made more job opportunities available to women. This has created interest to conduct studies on the effect of working lifestyle on pregnancy outcomes. Aim: This study was conducted with the aim to assess the relationship between mothers' working status as a social determinant and the incidence of low birth weight (LBW) of the newborn. Subjects and Methods: This case–control study was conducted on 500 women with normal weight infants (control group) and 250 women with LBW infants (case group) in selected hospitals in Tehran. Data were collected using a researcher-made questionnaire, designed to assess the effect of mothers' prenatal lifestyle, as a social determinant, on LBW of the newborn. A section of the questionnaire involved assessment of mother's working condition in terms of the work environment, activities, and job satisfaction. Data were analyzed using Chi-square and logistic regression tests. Results: LBW among employed mothers was 5 times more likely than unemployed ones (odds ratio = 5.35, P < 0.001). Unfavorable work conditions such as humid environment, contact with detergents, and being in one standing or sitting position for long hours were significantly associated with LBW (P < 0.001). Conclusion: The present study showed that unfavorable work conditions were associated with LBW; therefore, they need special attention. PMID:27057375

  11. A patient with primary hyperparathyroidism associated with familial hypocalciuric hypercalcemia induced by a novel germline CaSR gene mutation.

    PubMed

    Yabuta, Tomonori; Miyauchi, Akira; Inoue, Hiroyuki; Yoshida, Hiroshi; Hirokawa, Mitsuyoshi; Amino, Nobuyuki

    2009-04-01

    We report a patient with familial hypocalciuric hypercalcemia (FHH) associated with primary hyperparathyroidism (PHPT) and incidental papillary thyroid carcinoma. The patient showed hypercalcemia, high parathyroid hormone (PTH) levels and low urinary calcium excretion. A computed tomography (CT) scan revealed an enlarged parathyroid gland. Ultrasonography (US) and aspiration cytology revealed microcarcinoma of the left lobe of the thyroid gland. Screening studies of his family revealed that four of five family members had hypocalciuric hypercalcemia and normal PTH level. Sequencing analysis of the calcium sensing receptor gene revealed a novel heterozygous mutation (3193delA) in the patient and his family members with hypercalcemia, but one with normocalcemia. The patient underwent total thyroidectomy, central node dissection and extirpation of the enlarged parathyroid gland. Surgery is not indicated for FHH; however, FHH may be accompanied with parathyroid adenoma causing PHPT, as reported here, for which surgical treatment is indicated. PMID:19423460

  12. Genetic Determinants of Cardio-Metabolic Risk: A Proposed Model for Phenotype Association and Interaction

    PubMed Central

    Blackett, Piers R; Sanghera, Dharambir K

    2012-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus it follows that the genetics of dyslipidemia, obesity, and non-alcoholic fatty liver (NAFLD) disease are central in triggering progression of the syndrome to overt expression of disease traits, and have become a key focus of interest for early detection and for designing prevention and treatments. To support the “birds’ eye view” approach we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacological targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. PMID:23351585

  13. Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane

    PubMed Central

    Elazar, Assaf; Weinstein, Jonathan; Biran, Ido; Fridman, Yearit; Bibi, Eitan; Fleishman, Sarel Jacob

    2016-01-01

    Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self-association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers. DOI: http://dx.doi.org/10.7554/eLife.12125.001 PMID:26824389

  14. Genetic Determinants of Circulating Interleukin-1 Receptor Antagonist Levels and Their Association With Glycemic Traits

    PubMed Central

    Nuotio, Marja-Liisa; Shah, Sonia; Blankenberg, Stefan; Brunner, Eric J.; Carstensen, Maren; Gieger, Christian; Grallert, Harald; Jula, Antti; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, Christian; Peters, Annette; Prokisch, Holger; Raitakari, Olli; Rathmann, Wolfgang; Roden, Michael; Salmi, Marko; Schramm, Katharina; Swerdlow, Daniel; Tabak, Adam G.; Thorand, Barbara; Wareham, Nick; Wild, Philipp S.; Zeller, Tanja; Hingorani, Aroon D.; Witte, Daniel R.; Kumari, Meena; Perola, Markus; Salomaa, Veikko

    2014-01-01

    The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10−21] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10−17]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA–raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA–raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance. PMID:24969107

  15. Genetic determinants of circulating interleukin-1 receptor antagonist levels and their association with glycemic traits.

    PubMed

    Herder, Christian; Nuotio, Marja-Liisa; Shah, Sonia; Blankenberg, Stefan; Brunner, Eric J; Carstensen, Maren; Gieger, Christian; Grallert, Harald; Jula, Antti; Kähönen, Mika; Kettunen, Johannes; Kivimäki, Mika; Koenig, Wolfgang; Kristiansson, Kati; Langenberg, Claudia; Lehtimäki, Terho; Luotola, Kari; Marzi, Carola; Müller, Christian; Peters, Annette; Prokisch, Holger; Raitakari, Olli; Rathmann, Wolfgang; Roden, Michael; Salmi, Marko; Schramm, Katharina; Swerdlow, Daniel; Tabak, Adam G; Thorand, Barbara; Wareham, Nick; Wild, Philipp S; Zeller, Tanja; Hingorani, Aroon D; Witte, Daniel R; Kumari, Meena; Perola, Markus; Salomaa, Veikko

    2014-12-01

    The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10(-21)] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10(-17)]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA-raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA-raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance. PMID:24969107

  16. The Associative Meaning and Content Validity of Selected Elements from the Industrial Arts Curriculum Project's Taxonomy as Determined by Continued Word Association.

    ERIC Educational Resources Information Center

    Mason, Emmett Elwell

    Industrial management concepts in the taxonomy of the Industrial Arts Curriculum Project (IACP) at The Ohio State University were the focus of this study. The purposes were: (1) to determine the associative meanings which were held by manufacturing management personnel for 14 selected management concepts, (2) to determine the principal…

  17. Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia.

    PubMed

    Oest, Megan E; Gong, Bo; Esmonde-White, Karen; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A; Morris, Michael D

    2016-05-01

    As part of our ongoing efforts to understand underlying mechanisms contributing to radiation-associated bone fragility and to identify possible treatments, we evaluated the longitudinal effects of parathyroid hormone (PTH) treatment on bone quality in a murine model of limited field irradiation. We hypothesized PTH would mitigate radiation-induced changes in the chemical composition and structure of bone, as measured by microscope-based Raman spectroscopy. We further hypothesized that collagen crosslinking would be especially responsive to PTH treatment. Raman spectroscopy was performed on retrieved tibiae (6-7/group/time point) to quantify metrics associated with bone quality, including: mineral-to-matrix ratio, carbonate-to-phosphate ratio, mineral crystallinity, collagen crosslink (trivalent:divalent) ratio, and the mineral and matrix depolarization ratios. Irradiation disrupted the molecular structure and orientation of bone collagen, as evidenced by a higher collagen crosslink ratio and lower matrix depolarization ratio (vs. non-irradiated control bones), persisting until 12weeks post-irradiation. Radiation transiently affected the mineral phase, as evidenced by increased mineral crystallinity and mineral-to-matrix ratio at 4weeks compared to controls. Radiation decreased bone mineral depolarization ratios through 12weeks, indicating increased mineral alignment. PTH treatment partially attenuated radiation-induced increases in collagen crosslink ratio, but did not restore collagen or mineral alignment. These post-radiation matrix changes are consistent with our previous studies of radiation damage to bone, and suggest that the initial radiation damage to bone matrix has extensive effects on the quality of tissue deposited thereafter. In addition to maintaining bone quality, preventing initial radiation damage to the bone matrix (i.e. crosslink ratio, matrix orientation) may be critical to preventing late-onset fragility fractures. PMID:26960578

  18. Serum 25-hydroxyvitamin D and parathyroid hormone in relation to plasma B-type natriuretic peptide: the Hoorn Study

    PubMed Central

    van Ballegooijen, Adriana J; Visser, Marjolein; Snijder, Marieke B; Dekker, Jacqueline M; Nijpels, Giel; Stehouwer, Coen D A; Diamant, Michaela; Brouwer, Ingeborg A

    2012-01-01

    Objective A disturbed vitamin D–parathyroid hormone (PTH)–calcium axis may play a role in the pathogenesis of heart failure. Therefore, we investigated whether lower 25-hydroxyvitamin D (25(OH)D) and higher PTH are cross sectionally and after 8 years of follow-up associated with higher B-type natriuretic peptide (BNP) levels in older men and women. Design and methods We measured baseline 25(OH)D, PTH, and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was available in 2007–2009 in 278 subjects. Subjects were categorized according to season- and sex-specific quartiles of 25(OH)D and PTH at baseline. We studied the association of 25(OH)D and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Analyses were stratified by kidney function estimated glomerular filtration rate (eGFR; ≤60 ml/min per 1.73 m2) because of significant interaction. Results At baseline, subjects had a mean age of 69.9±6.6 years, mean 25(OH)D level was 52.2±19.5 nmol/l and mean PTH 6.1±2.4 pmol/l. Cross sectionally, 25(OH)D was associated with BNP in subjects with impaired kidney function (eGFR ≤60 ml/min) only. The association attenuated after adjustment for PTH. PTH was cross sectionally associated with BNP, also in subjects with impaired kidney function only: regression coefficient of highest quartile 9.9 pmol/l (95% confidence interval 2.5, 17.4) with a significant trend across quartiles. Neither 25(OH)D nor PTH was associated with BNP in longitudinal analyses. Conclusion This study showed overall no strong association between 25(OH)D and BNP. However, PTH was associated with BNP in subjects with impaired kidney function and may point to a potential role in myocardial function. PMID:23781303

  19. Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.

    PubMed

    Bi, Ruiye; Fan, Yi; Lauter, Kelly; Hu, Jing; Watanabe, Tomoyuki; Cradock, Jim; Yuan, Quan; Gardella, Thomas; Mannstadt, Michael

    2016-05-01

    Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 × 5 μg/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP-guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. © 2015 American Society for Bone and Mineral Research. PMID:26678919

  20. Endocrine tumors associated with the vagusnerve

    PubMed Central

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-01-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural-crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aorto-pulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID:27406876

  1. Endocrine tumors associated with the vagus nerve.

    PubMed

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-09-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID:27406876

  2. Gene-based analysis of rare and common variants to determine association with blood pressure.

    PubMed

    Liu, Xiaofeng; Beyene, Joseph

    2014-01-01

    Systolic blood pressure and diastolic blood pressure are known risk factors for cardiovascular diseases and understanding their genetic basis will have important public health implications. For rare variants, it is extremely challenging to make statistical inference for single-maker tests. Therefore, joint analysis of a set of variants has been proposed. In this paper, we applied recently proposed methods "test for testing the effect of an optimally weighted combination of variants" and "variable weight-TOW" to determine genetic regions that are associated with blood pressure. Then least absolute shrinkage and selection operator, as well as sparse partial least square methods, were used to identify significant markers within a gene or in intergenic regions. We investigated the effect of rare variants and common variants, and their combined effect. PMID:25519387

  3. Comparison of imaging methods for diagnosing enlarged parathyroid glands in chronic renal failure

    SciTech Connect

    Takagi, H.; Tominaga, Y.; Uchida, K.; Yamada, N.; Kano, T.; Kawai, M.; Morimoto, T.

    1985-07-01

    Three noninvasive imaging methods, CT, scintigraphy with /sup 201/TlCl and /sup 99m/TcO4-, and ultrasonography, were performed on 36 patients with chronic renal failure and secondary hyperparathyroidism. The patients subsequently underwent total parathyroidectomy and parathyroid autograft. The detection rates of the three methods for the 143 excised parathyroid glands were compared according to gland weight and location. Computed tomography detected 53.8% of all glands and 77.6% of 76 glands weighing more than 500 mg. Scintigraphy detected 51.0% of all glands and 77.6% of glands heavier than 500 mg. Ultrasonography detected 42.7% of all glands and 65.8% of glands heavier than 500 mg. The detection rate of upper glands was best with CT (53.5 and 87.9%): that of lower glands was best with scintigraphy (62.0 and 78.6%). Although the combination of the three methods diagnosed 66.4% of all glands and 89.5% of glands heavier than 500 mg, CT and scintigraphy, the best two combinations, visualized 64.3 and 88.2%.

  4. Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression

    NASA Technical Reports Server (NTRS)

    Partridge, N. C.; Bloch, S. R.; Pearman, A. T.

    1994-01-01

    Parathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate production of PTH or the related hormone, parathyroid hormone related protein (PTHrP), accounts for the majority of the causes of hypercalcemia. Both hormones act through the same receptor on the osteoblast to elicit enhanced bone resorption by the osteoclast. Thus, the osteoblast mediates the effect of PTH in the resorption process. In this process, PTH causes a change in the function and phenotype of the osteoblast from a cell involved in bone formation to one directing the process of bone resorption. In response to PTH, the osteoblast decreases collagen, alkaline phosphatase, and osteopontin expression and increases production of osteocalcin, cytokines, and neutral proteases. Many of these changes have been shown to be due to effects on mRNA abundance through either transcriptional or post-transcriptional mechanisms. However, the signal transduction pathway for the hormone to cause these changes is not completely elucidated in any case. Binding of PTH and PTHrP to their common receptor has been shown to result in activation of protein kinases A and C and increases in intracellular calcium. The latter has not been implicated in any changes in mRNA of osteoblastic genes. On the other hand activation of PKA can mimic all the effects of PTH; protein kinase C may be involved in some responses. We will discuss possible mechanisms linking PKA and PKC activation to changes in gene expression, particularly at the nuclear level.

  5. Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors

    SciTech Connect

    Fujiwara, Saeko; Yokoyama, Naokata; Sasaki, Hideo; Kodama, Kazunori; Sposto, R.; Shimaoka, Katsutaro; Shiraki, Mastaka

    1994-01-01

    To examines the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure. 21 refs., 3 figs., 6 tabs.

  6. Structure-Inherent Targeting of NIR Fluorophores for Parathyroid and Thyroid Gland Imaging

    PubMed Central

    Hyun, Hoon; Park, Min Ho; Owens, Eric A.; Wada, Hideyuki; Henary, Maged; Handgraaf, Hein J.M.; Vahrmeijer, Alexander L.; Frangioni, John V.; Choi, Hak Soo

    2014-01-01

    The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible create tissue-specific near-infrared fluorophores using the inherent chemical structure. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head/neck surgery, the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake in the specific glands after a single intravenous injection of only 0.06 mg kg−1 in a pig. Using a dual-channel near-infrared imaging system, we demonstrate the real-time, high-sensitivity, unambiguous identification of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays the foundation for head/neck surgery performed with increased precision and efficiency, and potentially lowers morbidity, and a general strategy for targeted near-infrared fluorophore development. PMID:25559343

  7. Is intraoperative parathyroid hormone monitoring necessary in symptomatic primary hyperparathyroidism with concordant imaging?

    PubMed Central

    Nair, C. Gopalakrishnan; Babu, Misha J. C.; Jacob, Pradeep; Menon, Riju; Mathew, Jimmy

    2016-01-01

    Introduction: Symptomatic primary hyperparathyroidism (PHPT) is still seen frequently in referral centers all over India. These patients require parathyroidectomy and this study aimed to assess the roll of intraoperative parathyroid hormone (PTH) assay when concordant results of two localization studies were available. Study Design: We analyzed the case records of patients who underwent parathyroidectomy for PHPT from January 2005 to June 2015. Results: Of 143 patients included in the study, technetium 99m methoxyisobutylisonitrate dual phase scintigraphy showed true positive images in 93.7% and high definition ultrasonography in 84.6% of patients. Concordance in localization studies was observed in 121 (84.6%) patients, successful parathyroidectomy was done in 117 (96.7%) patients with concordant localization studies. Intraoperative PTH monitoring showed 97.84% sensitivity and 75% specificity and predicted failure in 2 patients with concordant imaging. However, re-exploration was not successful in these patients. Conclusion: When concordant result is available between parathyroid scintigraphy and anatomical imaging surgical cure rate is high in trained hands. Re-exploration is unlikely to be successful since these patients require higher imaging. PMID:27366718

  8. Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas

    PubMed Central

    Sugi, Orie; Kimata, Naoki; Miwa, Naoko; Otsubo, Shigeru; Nitta, Kosaku; Akiba, Takashi

    2010-01-01

    We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain. PMID:25984040

  9. Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: report of one case.

    PubMed

    Radulescu, Dan; Chis, Bogdan; Donca, Valer; Munteanu, Valentin

    2014-07-01

    Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48 mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma. PMID:25378013

  10. Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

    PubMed Central

    Kumar, Amit; Baumann, Monika; Balbach, Jochen

    2016-01-01

    Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required. PMID:26932583

  11. Dimeric Arrangement of the Parathyroid Hormone Receptor and a Structural Mechanism for Ligand-induced Dissociation

    SciTech Connect

    Pioszak, Augen A.; Harikumar, Kaleeckal G.; Parker, Naomi R.; Miller, Laurence J.; Xu, H. Eric

    2010-06-25

    The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an {alpha}-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein.

  12. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    PubMed Central

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  13. Lithology determination from well logs with fuzzy associative memory neural network

    SciTech Connect

    Chang, H.C.; Chen, H.C.; Fang, J.H.

    1997-05-01

    An artificial intelligence technique of fuzzy associative memory is used to determine rock types from well-log signatures. Fuzzy associative memory (FAM) is a hybrid of neutral network and fuzzy expert system. This new approach combines the learning ability of neural network and the strengths of fuzzy linguistic modeling to adaptively infer lithologies from well-log signatures based on (1) the relationships between the lithology and log signature that the neural network have learned during the training and/or (2) geologist`s knowledge about the rocks. The method is applied to a sequence of the Ordovician rock units in northern Kansas. This paper also compares the performances of two different methods, using the same data set for meaningful comparison. The advantages of FAM are (1) expert knowledge acquired by geologists is fully utilized; (2) this knowledge is augmented by the neural network learning from the data, when available; and (3) FAM is transparent in that the knowledge is explicitly stated in the fuzzy rules.

  14. Glycan binding avidity determines the systemic fate of adeno-associated virus type 9.

    PubMed

    Shen, Shen; Bryant, Kelli D; Sun, Junjiang; Brown, Sarah M; Troupes, Andrew; Pulicherla, Nagesh; Asokan, Aravind

    2012-10-01

    Glycans are key determinants of host range and transmissibility in several pathogens. In the case of adeno-associated viruses (AAV), different carbohydrates serve as cellular receptors in vitro; however, their contributions in vivo are less clear. A particularly interesting example is adeno-associated virus serotype 9 (AAV9), which displays systemic tropism in mice despite low endogenous levels of its primary receptor (galactose) in murine tissues. To understand this further, we studied the effect of modulating glycan binding avidity on the systemic fate of AAV9 in mice. Intravenous administration of recombinant sialidase increased tissue levels of terminally galactosylated glycans in several murine tissues. These conditions altered the systemic tropism of AAV9 into a hepatotropic phenotype, characterized by markedly increased sequestration within the liver sinusoidal endothelium and Kupffer cells. In contrast, an AAV9 mutant with decreased glycan binding avidity displayed a liver-detargeted phenotype. Altering glycan binding avidity also profoundly affected AAV9 persistence in blood circulation. Our results support the notion that high glycan receptor binding avidity appears to impart increased liver tropism, while decreased avidity favors systemic spread of AAV vectors. These findings may not only help predict species-specific differences in tropism for AAV9 on the basis of tissue glycosylation profiles, but also provide a general approach to tailor AAV vectors for systemic or hepatic gene transfer by reengineering capsid-glycan interactions. PMID:22787229

  15. An analytical scheme for determining forms of sulphur in oil shales and associated rocks

    USGS Publications Warehouse

    Tuttle, M.L.; Goldhaber, M.B.; Williamson, D.L.

    1986-01-01

    An analytical scheme for determining various forms of sulphur in oil shales and associated rocks is presented. Acid-soluble sulphate, sulphur contained in monosulphide and in disulphide minerals, and organically-bound sulphur are all quantitatively recovered as separate fractions. Finely-ground oil-shale samples are treated in an inert atmosphere with 6M hydrochloric acid to dissolve the acid-soluble sulphate minerals and form H2S from the decomposition of monosulphide minerals. The acid-soluble sulphate is precipitated as barium sulphate and the H2S is collected and weighed as silver sulphide. Disulphide minerals in the solid residue from the acid treatment are reduced by an acidified Cr(II) solution in an inert atmosphere, releasing the sulphide as H2S. The H2S is collected as silver sulphide. An Eschka fusion oxidizes and solubilizes all sulphur remaining within the Cr(II)-treated residue. This sulphate represents organically-bound sulphur and is collected as barium sulphate. The analytical procedures have been verified by using 57Fe Mo??ssbauer spectroscopy. Good agreement between the chemical and Mo??ssbauer data substantiated the sequential removal of the forms of sulphur and also demonstrated the ability of Mo??ssbauer spectroscopy to determine the absolute quantities of iron present in specific minerals. ?? 1986.

  16. Intermolecular associations determine the dynamics of the circadian KaiABC oscillator

    PubMed Central

    Qin, Ximing; Byrne, Mark; Mori, Tetsuya; Zou, Ping; Williams, Dewight R.; Mchaourab, Hassane; Johnson, Carl Hirschie

    2010-01-01

    Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute circadian oscillations in vitro. At least three molecular properties oscillate during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic activity of KaiC, and assembly/disassembly of intermolecular complexes among KaiA, KaiB, and KaiC. We found that the intermolecular associations determine key dynamic properties of this in vitro oscillator. For example, mutations within KaiB that alter the rates of binding of KaiB to KaiC also predictably modulate the period of the oscillator. Moreover, we show that KaiA can bind stably to complexes of KaiB and hyperphosphorylated KaiC. Modeling simulations indicate that the function of this binding of KaiA to the KaiB•KaiC complex is to inactivate KaiA's activity, thereby promoting the dephosphorylation phase of the reaction. Therefore, we report here dynamics of interaction of KaiA and KaiB with KaiC that determine the period and amplitude of this in vitro oscillator. PMID:20679240

  17. Fluorescence Microscopy Methods for Determining the Viability of Bacteria in Association with Mammalian Cells

    PubMed Central

    Johnson, M. Brittany; Criss, Alison K.

    2013-01-01

    Central to the field of bacterial pathogenesis is the ability to define if and how microbes survive after exposure to eukaryotic cells. Current protocols to address these questions include colony count assays, gentamicin protection assays, and electron microscopy. Colony count and gentamicin protection assays only assess the viability of the entire bacterial population and are unable to determine individual bacterial viability. Electron microscopy can be used to determine the viability of individual bacteria and provide information regarding their localization in host cells. However, bacteria often display a range of electron densities, making assessment of viability difficult. This article outlines protocols for the use of fluorescent dyes that reveal the viability of individual bacteria inside and associated with host cells. These assays were developed originally to assess survival of Neisseria gonorrhoeae in primary human neutrophils, but should be applicable to any bacterium-host cell interaction. These protocols combine membrane-permeable fluorescent dyes (SYTO9 and 4',6-diamidino-2-phenylindole [DAPI]), which stain all bacteria, with membrane-impermeable fluorescent dyes (propidium iodide and SYTOX Green), which are only accessible to nonviable bacteria. Prior to eukaryotic cell permeabilization, an antibody or fluorescent reagent is added to identify extracellular bacteria. Thus these assays discriminate the viability of bacteria adherent to and inside eukaryotic cells. A protocol is also provided for using the viability dyes in combination with fluorescent antibodies to eukaryotic cell markers, in order to determine the subcellular localization of individual bacteria. The bacterial viability dyes discussed in this article are a sensitive complement and/or alternative to traditional microbiology techniques to evaluate the viability of individual bacteria and provide information regarding where bacteria survive in host cells. PMID:24056524

  18. Functional Parathyroid Cyst: A Rare Cause of Malignant Hypercalcemia with Primary Hyperparathyroidism—A Case Report and Review of the Literature

    PubMed Central

    Khan, Areej; Khan, Yusra; Raza, Shahzad; Akbar, Ghulam; Khan, Monis; Diwan, Nauman; Rizvi, Wajih

    2012-01-01

    Parathyroid cysts are rare lesions found in the neck and anterior mediastinum. They are often nonfunctional (>90%) and rarely in the functional form. This paper discusses a case of severe hypercalcemia (23 mg/dL) secondary to a rare functional parathyroid cyst. The patient was later found to have a hemorrhagic cyst with compression of the right recurrent laryngeal nerve. Preoperative diagnosis of the lesion was parathyroid carcinoma. However, reexploration of the parathyroid mass along with microscopic study confirmed the diagnosis of a parathyroid cyst. Following cystectomy, the patient restored her baseline functional status with preservation of the right recurrent laryngeal nerve. Postoperative followup three years later showed no evidence of cyst recurrence. This paper illustrates the rare presentation of parathyroid functional cysts with severe hypercalcemia and primary hyperparathyroidism. Physicians should be aware of the presence of hemorrhage, inflammation, and compressive symptoms in these cysts which mimic parathyroid carcinoma. These patients should be managed with aggressive medical and surgical intervention. PMID:22431942

  19. Treatment study of distal femur for parathyroid hormone (1-34) and β-tricalcium phosphate on bone formation in critical size defects in rats.

    PubMed

    Tao, Zhou-Shan; Qiang, Zhou; Tu, Kai-kai; Huang, Zheng-liang; Xu, Hong-ming; Sun, Tao; Lv, Yang-Xun; Cui, Wei; Yang, Lei

    2015-10-01

    The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34), a surgically implanted synthetic β-tricalcium phosphate bone biomaterial serving as a matrix to support new bone formation. Twelve weeks after bilateral ovariectomy, all rats underwent bone defect in the distal femurs, and β-tricalcium phosphate was implanted into critical sized defects. After defect operation, all animals were randomly divided into four groups and received following subcutaneous injections until death at four and eight weeks: sham rats (group ST); sham rats + parathyroid hormone, 30 µg/kg, three times a week (group SPT); OVX rats (group OT); and OVX rats + parathyroid hormone (group OPT). The distal femurs of rats were harvested for evaluation. The treatment group demonstrating the highest levels of new bone formation was the defects treated with parathyroid hormone as assessed by micro-computed tomography, biomechanical strength, and histological analysis for sham rats. Furthermore, parathyroid hormone showed a stronger effect on accelerating the degradation of β-tricalcium phosphate. Osteoporosis can limit the function of parathyroid hormone and/or β-tricalcium phosphate. The results from our study demonstrate that combination of parathyroid hormone and β-tricalcium phosphate brings better effect to bone tissue repair in non-osteoporosis and/or osteoporosis status. PMID:26116022

  20. Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection: A Prospective Colonoscopy Study.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Luk, Arthur K C; Tang, Raymond S Y; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2016-01-01

    The predictors of poor bowel preparation in colorectal cancer screening participants have not been adequately studied, and the association between the quality of bowel preparation and adenoma detection has not been firmly established. This study examined the determinants of poor bowel preparation, and evaluated its relationship with adenoma detection.We included subjects aged between 50 and 70 years who received colonoscopy between 2008 and 2014 in a colorectal cancer screening program in Hong Kong. The quality of the bowel preparation was assessed by colonoscopists, and the factors associated with poor bowel cleansing were evaluated by a binary logistic regression analysis. A multivariate regression model was constructed to evaluate if poor bowel preparation was associated with detection of colorectal neoplasia.From 5470 screening participants (average age 57.7 years, SD 4.9), 1891 (34.6%) had poor or fair bowel preparation. The average cecal intubation time was 7.0 minutes (SD 5.4; range 1.22-36.9 minutes) and the average colonoscopy withdrawal time was 10.8 minutes (SD 6.9; range 6.0-107.0 minutes). Among all, 26.5% had colorectal neoplasia and 5.5% had advanced neoplasia. Older age (≥60 years; adjusted odds ratio [AOR] = 1.19-1.38, P = 0.02-0.04), male sex (AOR = 1.38, 95% confidence interval [CI] 1.19-1.60, P < 0.001), and current smoking (AOR = 1.41, 95% CI 1.14-1.75, P = 0.002) were significantly associated with poor/fair bowel preparation. Poorer cleansing resulted in significantly lower detection rate of neoplasia (AOR = 0.35-0.62) and advanced neoplasia (AOR = 0.36-0.50) irrespective of polyp size.Steps to improve proper procedures of bowel preparation are warranted, especially among subjects at risk of poor bowel preparation. Strategies should be implemented to improve bowel cleansing, which is now demonstrated as a definite quality indicator. PMID:26765402

  1. Video Assisted Thoracoscopic Surgery (VATS) for Excision of an Ectopic Anterior Mediastinal Intra-Thymic Parathyroid Adenoma.

    PubMed

    Naik, Dukhabandhu; Jebasingh, Kumaradoss Felix; Ramprasath; Roy, Gnanamuthu Birla; Paul, Mazhuvanchary Jacob

    2016-06-01

    Ectopic anterior mediastinal parathyroid adenoma is a rare cause of Primary Hyperparathyroidism (PHPT). Imaging studies such as Technetium-99m ((99m)Tc) sestamibi parathyroid scan along with a Single Photon Emission Computerized Tomogram (SPECT), and contrast enhanced Computerized Tomogram (CT) of the neck and thorax can precisely localize the ectopic mediastinal parathyroid adenoma. We report a 40-year-old gentleman who presented with persistent pain in the right shoulder following trivial trauma. His biochemical investigations showed an elevated serum calcium of 11.6mg% (Normal: 8.3-10.4 mg%) along with an elevated iPTH of 1443 pg/ml (normal: 8-70 pg/ml) which were suggestive of primary hyperparathyroidism. The localization studies revealed an ectopic cystic parathyroid adenoma in the anterior mediastinum that was not accessible from the neck. He underwent a Video Assisted Thoracoscopic (VAT) excision procedure with normalization of serum calcium and an uncomplicated recovery. The VAT approach is a successful minimally invasive technique for mediastinal parathyroidectomy. PMID:27504353

  2. [Initial experience in intraoperative radiolocalization of the parathyroid adenoma with freehand SPECT and comparative assessment with portable gamma-camera].

    PubMed

    Casáns-Tormo, I; Prado-Wohlwend, S; Díaz-Expósito, R; Cassinello-Fernández, N; Ortega-Serrano, J

    2015-01-01

    Initial experience is presented by using freehand SPECT in the intraoperative radiolocalization of a parathyroid adenoma in 2 patients, one which was mediastinal. There is only one previous publication including 3 patients with parathyroid adenomas in usual parathyroid localizations. We also report for the first time a comparative assessment of results with portable gammacamera during the same surgery. In the operating room, we obtained images with portable gamma-camera and 3 D reconstruction with freehand SPECT from 15 min after iv injection of 5 mCi of (99m)Tc-MIBI. Both devices enabled the 2 adenomas to be detected intraoperatively, as well as checking activity of the excised gland and absence of significant uptake in surgical bed, with confirmation by intraoperative pre-postsurgical PTH levels, pathology and clinical follow-up for 10 months. Both devices accurately located the parathyroid adenomas intraoperatively, as well as confirmation of their extirpation, but freehand SPECT provided additional information of adenoma depth (mm) from the skin border, very useful for minimally invasive radio-guided surgery. PMID:25577326

  3. Parathyroid hormone, calcitonin, and vitamin D 1974: Present status of physiological studies and analysis of calcium homeostasis

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.; Swenson, K. G.

    1975-01-01

    The role of parathyroid hormone, calcitonin, and vitamin D in the control of calcium and bone metabolism was studied. Particular emphasis was placed on the physiological adaptation to weightlessness and, as a potential model for this purpose, on the immobilization characteristic of space flight or prolonged bed rest. The biosynthesis, control of secretion, and metabolism of these hormonal agents is considered.

  4. Video Assisted Thoracoscopic Surgery (VATS) for Excision of an Ectopic Anterior Mediastinal Intra-Thymic Parathyroid Adenoma

    PubMed Central

    Naik, Dukhabandhu; Jebasingh, Kumaradoss Felix; Ramprasath; Roy, Gnanamuthu Birla

    2016-01-01

    Ectopic anterior mediastinal parathyroid adenoma is a rare cause of Primary Hyperparathyroidism (PHPT). Imaging studies such as Technetium-99m (99mTc) sestamibi parathyroid scan along with a Single Photon Emission Computerized Tomogram (SPECT), and contrast enhanced Computerized Tomogram (CT) of the neck and thorax can precisely localize the ectopic mediastinal parathyroid adenoma. We report a 40-year-old gentleman who presented with persistent pain in the right shoulder following trivial trauma. His biochemical investigations showed an elevated serum calcium of 11.6mg% (Normal: 8.3-10.4 mg%) along with an elevated iPTH of 1443 pg/ml (normal: 8-70 pg/ml) which were suggestive of primary hyperparathyroidism. The localization studies revealed an ectopic cystic parathyroid adenoma in the anterior mediastinum that was not accessible from the neck. He underwent a Video Assisted Thoracoscopic (VAT) excision procedure with normalization of serum calcium and an uncomplicated recovery. The VAT approach is a successful minimally invasive technique for mediastinal parathyroidectomy. PMID:27504353

  5. Successful Localization of Abnormal Parathyroid Gland Using Ultrasound-Guided Methylene Blue Dye Injection in the Reoperative Neck.

    PubMed

    Haciyanli, Mehmet; Koruyucu, Melike Bedel; Erdoğan, Nezahat Karaca; Dere, Ozcan; Sarı, Erdem; Kumkumoğlu, Yusuf; Tavusbay, Cengiz; Kamer, Erdinc

    2015-12-01

    Persistent or recurrent hyperparathyroidism is a challenging problem for endocrine surgeons. The aim of this study was to review our experience using ultrasound-guided (US-G) methylene blue dye injection for the localization and removal of abnormal parathyroid glands in patients having primary hyperparathyroidism and previous neck surgery. Between January 2012 and May 2013, six consecutive patients with primary hyperparathyroidism (PHPT) and previous neck surgery underwent focused parathyroidectomy with the use of US-G methylene blue dye injections to localize the presumed parathyroid adenoma were included in the study. We analyzed the data of six patients who underwent reoperative parathyroid surgery using US-G methylene blue dye injection retrospectively. The dye injection was performed just prior to surgery. All patients were successfully treated for their hyperparathyroidism which was confirmed by at least 50 % drop in intraoperative parathormone level 10 min after resection. There were no complications related with US-G dye injection or with surgery. US-G methylene blue dye injection is a cheap, safe, and effective method for localization of diseased parathyroid glands and guiding surgery in the reoperative neck. PMID:27011517

  6. Bone marrow ablation demonstrates that excess endogenous parathyroid hormone plays distinct roles in trabecular and cortical bone.

    PubMed

    Yan, Jun; Sun, Weiwei; Zhang, Jing; Goltzman, David; Miao, Dengshun

    2012-07-01

    Mice null for Cyp27b1, which encodes the 25-hydroxyvitamin D-1α-hydroxylase [1α(OH)ase(-/-) mice], lack 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and have hypocalcemia and high parathyroid hormone (PTH) secretion. Intermittent, exogenous PTH is anabolic for bone. To determine the effect of the chronic excess endogenous PTH on osteogenesis and bone turnover, bone marrow ablations (BMX) were performed in tibiae and femurs of 6-week-old 1α(OH)ase(-/-) mice and in wild-type (WT) controls. Newly formed bone tissue was analyzed at 1, 2, and 3 weeks after BMX. BMX did not alter the higher levels of PTH in 1α(OH)ase(-/-) mice. In the marrow cavity, trabecular volume, osteoblast number, alkaline phosphatase-positive areas, type I collagen-positive areas, bone formation-related genes, and protein expression levels all increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. Osteoclast numbers and surface and ratio of RANKL/OPG-relative mRNA levels decreased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. In the cortex, alkaline phosphatase-positive osteoblasts and osteoclast numbers increased significantly after BMX in 1α(OH)ase(-/-) mice, compared with WT. These results demonstrate that chronic excess endogenous PTH exerts an anabolic role in trabecular bone by stimulating osteogenic cells and reducing bone resorption, but plays a catabolic role in cortical bone by enhancing bone turnover with an increase in resorption. PMID:22640808

  7. Preparation and in vivo evaluation of an orally available enteric-microencapsulated parathyroid hormone (1-34)-deoxycholic acid nanocomplex

    PubMed Central

    Hwang, Seung Rim; Seo, Dong-Hyun; Byun, Youngro; Park, Jin Woo

    2016-01-01

    The N-terminal 34-amino-acid peptide fragment of human parathyroid hormone PTH (1-34), is used clinically to treat osteoporosis; however, it is currently administered by a once-daily subcutaneous injection, resulting in poor patient compliance. We have developed enteric microcapsules containing an ionic nanocomplex between PTH (1-34) and lysine-linked deoxycholic acid (LysDOCA) for the oral delivery of PTH (1-34). We measured the particle size of the PTH/LysDOCA complex and assessed its biological activity by determining the cAMP content in MC3T3-E1 cells. We also assessed its permeability across a Caco-2 cell monolayer and the bioavailability of the intrajejunally administered PTH/LysDOCA complex compared with PTH (1-34) in rats. In addition, the antiosteoporotic activity of the PTH/LysDOCA complex, encapsulated in an enteric carrier by coaxial ultrasonic atomization, was evaluated after it was orally administered to ovariectomized (OVX) rats. The formation of an ionic complex between PTH (1-34) and LysDOCA produced nanoparticles of diameter 33.0±3.36 nm, and the bioactivity of the complex was comparable with that of PTH (1-34). The Caco-2 cell permeability and AUClast value of the PTH/LysDOCA (1:10) nanocomplex increased by 2.87- and 16.3-fold, respectively, compared with PTH (1-34) alone. Furthermore, the OVX rats treated with oral PTH/LysDOCA-loaded enteric microcapsules showed an increase in bone mineral density (159%), bone volume fraction (175%), and trabecular number (174%) compared with those in the OVX control group. Therefore, the PTH/LysDOCA nanocomplex oral delivery system is a promising treatment modality for osteoporosis because it improves osteogenesis and trabecular connectivity. PMID:27621618

  8. Preparation and in vivo evaluation of an orally available enteric-microencapsulated parathyroid hormone (1-34)-deoxycholic acid nanocomplex.

    PubMed

    Hwang, Seung Rim; Seo, Dong-Hyun; Byun, Youngro; Park, Jin Woo

    2016-01-01

    The N-terminal 34-amino-acid peptide fragment of human parathyroid hormone PTH (1-34), is used clinically to treat osteoporosis; however, it is currently administered by a once-daily subcutaneous injection, resulting in poor patient compliance. We have developed enteric microcapsules containing an ionic nanocomplex between PTH (1-34) and lysine-linked deoxycholic acid (LysDOCA) for the oral delivery of PTH (1-34). We measured the particle size of the PTH/LysDOCA complex and assessed its biological activity by determining the cAMP content in MC3T3-E1 cells. We also assessed its permeability across a Caco-2 cell monolayer and the bioavailability of the intrajejunally administered PTH/LysDOCA complex compared with PTH (1-34) in rats. In addition, the antiosteoporotic activity of the PTH/LysDOCA complex, encapsulated in an enteric carrier by coaxial ultrasonic atomization, was evaluated after it was orally administered to ovariectomized (OVX) rats. The formation of an ionic complex between PTH (1-34) and LysDOCA produced nanoparticles of diameter 33.0±3.36 nm, and the bioactivity of the complex was comparable with that of PTH (1-34). The Caco-2 cell permeability and AUClast value of the PTH/LysDOCA (1:10) nanocomplex increased by 2.87- and 16.3-fold, respectively, compared with PTH (1-34) alone. Furthermore, the OVX rats treated with oral PTH/LysDOCA-loaded enteric microcapsules showed an increase in bone mineral density (159%), bone volume fraction (175%), and trabecular number (174%) compared with those in the OVX control group. Therefore, the PTH/LysDOCA nanocomplex oral delivery system is a promising treatment modality for osteoporosis because it improves osteogenesis and trabecular connectivity. PMID:27621618

  9. Topogenesis of a nucleolar protein: determination of molecular segments directing nucleolar association.

    PubMed

    Zirwes, R F; Kouzmenko, A P; Peters, J M; Franke, W W; Schmidt-Zachmann, M S

    1997-02-01

    To identify the element(s) in nucleolar proteins which determine nucleolus-specific topogenesis, we have used different kinds of cDNA constructs encoding various chimeric combinations of mutants of the constitutive nucleolar protein NO38 (B23): 1) with an amino terminally placed short "myc tag"; 2) with two different carboxyl terminally attached large alpha-helical coiled coil structures, the lamin A rod domain or the rod domain of vimentin; 3) with the sequence-related nucleoplasmic histone-binding protein nucleo-plasmin; and 4) with the soluble cytoplasmic protein pyruvate kinase. To avoid the problem of formation of complexes with endogenous wild-type (wt) molecules and "piggyback" localization, special care was taken to secure that the mutants and chimeras used did not oligomerize as is typical of protein NO38 (B23). Using microinjection and transfection of cultured cells, we found that the segment comprising the amino-terminal 123 amino acids (aa) alone was sufficient to effect nucleolar accumulation of the construct molecules, including the chimeras with the entire rod domains of lamin A and vimentin. However, when the amino-terminal 109 aa were deleted, the molecules still associated with the nucleolus. The results of further deletion experiments and of domain swaps with nucleoplasmin all point to the topogenic importance of two independent molecular regions located at both the amino- and carboxyl-terminal end. Our definition of dominant elements determining the nucleolar localization of protein NO38 (B23) as well as of diverse nonnucleolar proteins will help to identify its local binding partner(s) and functions, the construction of probes examining other proteins or sequence elements within the nucleolar microenvironment, and the generation of cells with an altered nuclear architecture. PMID:9190204

  10. ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

    PubMed

    2003-01-01

    ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with

  11. Habitual Sleep Duration Associated with Self-Reported and Objectively-Determined Cardiometabolic Risk Factors

    PubMed Central

    Grandner, Michael A.; Chakravorty, Subhajit; Perlis, Michael L.; Oliver, Linden; Gurubhagavatula, Indira

    2013-01-01

    and hypertension is strongest among non-Hispanic Whites, Blacks/African-Americans, and non-Mexican Hispanics/Latinos. Conclusions Short sleep duration is associated with self-reported and objectively-determined adverse cardiometabolic outcomes, even after adjustment for many covariates. Also, these patterns of risk depend on race/ethnicity. PMID:24333222

  12. Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R

    PubMed Central

    LIU, SHUANGXIN; ZHU, WEIPING; LI, SIJIA; MA, JIANCHAO; ZHANG, HUITAO; LI, ZHONGHE; ZHANG, LI; ZHANG, BIN; LI, ZHUO; LIANG, XINLING; SHI, WEI

    2016-01-01

    The vacuolar-type H+ adenosine triphosphatase (V-ATPase) plays an important role in cellular acidification and bone resorption by osteoclasts. However, the direct effect of bovine parathyroid hormone (bPTH) on V-ATPase has not yet been elucidated. The aim of the present study was to assess the effects of bPTH on V-ATPase and osteoclasts. Osteoclasts from bone marrow (BM)-derived monocytes of C57BL/6 mice were cultured with or without bPTH. The mRNA and protein expression levels of the V-ATPase a3-subunit and d2-subunit (by RT-qPCR and western blot analysis), V-ATPase activity (using the V type ATPase Activity Assay kit) and the bone resorption function of osteoclasts (by bone resorption assay) were examined following treatment with various concentrations of bPTH (0.1, 1.0, 10 and 100 ng/ml) alone or with bPTH and its inhibitor, bafilomycin A1. Furthermore, the expression of parathyroid hormone (PTH) receptors in osteoclasts was also detected. The results revealed that the mRNA and protein expression levels of V-ATPase a3-subunit and d2-subunit increased in a dose-dependent manner, paralleling the level of bPTH present. In addition, an increase in the concentration of bPTH was accompanied by the increased resorption capability of osteoclasts, whereas bone resorption was inhibited in the presence of bafilomycin A1. In addition, we confirmed the existence of parathyroid hormone 1 receptor (PTH1R) in osteoclasts using three different methods (RT-qPCR, western blot analysis and immunofluorescence staining). We found that bPTH enhanced the bone resorption capability of osteoclasts by modulating the expression of V-ATPase subunits, intracellular acidification and V-ATPase activity. Thus, we propose that PTH has a direct effect on osteoblasts and osteoclasts, and that this effect is mediated through PTH1R, thus contributing to bone remodeling. PMID:26647715

  13. Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in cultured bovine parathyroid cells.

    PubMed

    Sugimoto, T; Ritter, C; Slatopolsky, E; Morrissey, J

    1988-06-01

    There is evidence that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] affects phospholipid metabolism of intestine, kidney, and bone. There are no such studies concerning the parathyroid gland, which is also a target tissue for 1,25-(OH)2D3. In this investigation we examined the effect of 1,25-(OH)2D3 on the incorporation of radiolabeled choline, inositol, serine, and ethanolamine into the phospholipids of cultured bovine parathyroid cells. Treatment with 10(-8) M 1,25-(OH)2D3 for 48 h caused a significant decrease in [14C]choline incorporation, although there were no differences in the incorporation of radiolabeled inositol, serine, or ethanolamine. Time-course and dose-response evaluations of the 1,25-(OH)2D3 effect revealed that the decrease in [14C]choline incorporation was seen within 12 h of incubation and occurred with as little as 10(-9) M, respectively. In contrast, neither 10(-7) M 25-hydroxyvitamin D3 nor 10(-7) M 24,25-(OH)2D3 caused significant changes in [14C]choline incorporation. When 5 X 10(-6) M cycloheximide was added to the medium, the inhibitory effect of 1,25-(OH)2D3 on [14C]choline incorporation was completely abolished. A significant decrease in phosphatidylcholine content was observed after treatment with 10(-8) M 1,25-(OH)2D3 for 96 h. 1,25-(OH)2D3 did not cause a dramatic change in the fatty acid composition of the phosphatidylcholine. The present studies demonstrate that in parathyroid cells 1,25-(OH)2D3 causes a decrease in [14C]choline incorporation, which could be due to a decrease in the synthesis of phosphatidylcholine or increased degradation. This effect is specific for 1,25-(OH)2D3 and requires new protein synthesis. PMID:3131114

  14. Expression of HSV-1 Receptors in EBV-Associated Lymphoproliferative Disease Determines Susceptibility to Oncolytic HSV

    PubMed Central

    Wang, Pin-Yi; Currier, Mark A; Hansford, Loen; Kaplan, David; Chiocca, E. Antonio; Uchida, Hiroaki; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C.; van Kuppevelt, Toin H.; Mo, Xiaokui; Cripe, Timothy P

    2012-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. Because PKR is a major cellular defense against Herpes simplex virus, and oncolytic HSV-1 (oHSV) mutants have shown promising anti-tumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was most susceptible, NB122R was intermediate, and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas down-regulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a neuroblastoma cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases due to low virus receptor expression but also due to intact anti-viral PKR signaling. PMID:23254370

  15. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease

    PubMed Central

    Miyazaki, Márcia I.; Chiminacio Neto, Nelson; Padeski, Marcela C.; Barros, Ana Cláudia M.

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy. PMID:26745156

  16. Parathyroid hyperplasia

    MedlinePlus

    Patients with a family history of the MEN syndromes may want to have genetic screening to check for the defective gene. Those who have the defective gene may have routine screening tests to detect any early symptoms.

  17. Parathyroid Disorders

    MedlinePlus

    ... much phosphorous. Causes include injury to the glands, endocrine disorders, or genetic conditions. Treatment is aimed at restoring the balance of calcium and phosphorous. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  18. Parathyroid cancer

    MedlinePlus

    ... 2014 Updated by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  19. Parathyroid biopsy

    MedlinePlus

    ... adenoma Update Date 7/30/2014 Updated by: John A. Daller, MD, PhD, Department of Surgery, University ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Contact ...

  20. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    PubMed Central

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  1. Changes in parathyroid hormone receptor binding affinity during egg laying: implications for calcium homeostasis in chicken.

    PubMed

    Yasuoka, T; Kawashima, M; Takahashi, T; Iwata, A; Oka, N; Tanaka, K

    1996-12-01

    Parathyroid hormone (PTH) receptor bindings were examined in the membrane fraction of the calvaria and the kidney of the hen by the use of [125I]PTH-related protein (PTHrP) binding assays. The binding specificity, reversibility, and saturation of the receptor were demonstrated. The equilibrium dissociation constant (Kd) and the maximum binding capacity (Bmax) were obtained by Scatchard analyses. In both calvaria and kidney, Kd and Bmax values decreased at 3 h before oviposition in egg-laying hens, but not in nonlaying hens. Administration of 17 beta-estradiol or progesterone in vivo caused a decrease in the Kd and Bmax values. Ionized calcium concentrations in the blood plasma showed a decrease at 13 h before oviposition. The results suggest that the PTH receptor binding in the calvaria and the kidney is affected by ovarian steroid hormones and may play a role in maintaining the calcium homeostasis in the egg-laying hen. PMID:8970893

  2. Effect of propranolol and metoprolol on parathyroid hormone and calcitonin secretions in uraemic patients.

    PubMed Central

    Coevoet, B; Desplan, C; Sebert, J L; Makdassi, R; Andrejak, M; Gheerbrant, J D; Tolani, M; Calmette, C; Moukhtar, M S; Fournier, A

    1980-01-01

    Nine uraemic patients not being treated by dialysis received intravenous propranolol 1 microgram/kg/min for 85 minutes after a priming dose of 1 mg. Fifteen days later, six of them received intravenous metoprolol 1.2 microgram/kg/min after a priming dose of 1.2 mg. Plasma concentrations of parathyroid hormone (PTH) and calcitonin fell significantly after propranolol but not after metoprolol, whereas no change in plasma concentrations of ionised calcium and phosphate occurred with either drug. Heart rate fell similarly with both drugs. The fact that propranolol acutely suppressed PTH and calcitonin secretion in uraemic patients indicates that further studies are warranted to assess the long-term effects of the drug on the secretion of these hormones and on renal osteodystrophy. The contrast between the responses to propranolol and metoprolol supports the concept that PTH and calcitonin secretion is modulated through specific beta 2-receptors. PMID:7388535

  3. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    PubMed

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption. PMID:27068606

  4. 4D MRI for the Localization of Parathyroid Adenoma: A Novel Method in Evolution.

    PubMed

    Merchavy, Shlomo; Luckman, Judith; Guindy, Michal; Segev, Yoram; Khafif, Avi

    2016-03-01

    The sestamibi scan (MIBI) and ultrasound (US) are used for preoperative localization of parathyroid adenoma (PTA), with sensitivity as high as 90%. We developed 4-dimensional magnetic resonance imaging (4D MRI) as a novel tool for identifying PTAs. Eleven patients with PTA were enrolled. 4D MRI from the mandible to the aortic arch was used. Optimization of the timing of image acquisition was obtained by changing dynamic and static sequences. PTAs were identified in all except 1 patient. In 9 patients, there was a complete match between the 4D MRI and the US and MIBI, as well as with the operative finding. In 1 patient, the adenoma was correctly localized by 4D MRI, in contrast to the US and MIBI scan. The sensitivity of the 4D MRI was 90% and after optimization, 100%. Specificity was 100%. We concluded that 4D MRI is a reliable technique for identification of PTAs, although more studies are needed. PMID:26598499

  5. Development of monoclonal antibodies against parathyroid hormone: genetic control of the immune response to human PTH

    SciTech Connect

    Nussbaum, S.R.; Lin, C.S.; Potts, J.T. Jr.; Rosenthal, A.S.; Rosenblatt, M.

    1985-01-01

    Seventeen monocloanl antibodies against the aminoterminal portion of parathyroid hormone (PTH) were generated by using BALB/c mouse for immunization fully biologically active synthetic human PTH-(1-34) and bovine PTH-(1-84) as immunogens, monoclonal antibody methods, and a solid-phase screening assay. Isotypic analysis of these monoclonal antibodies was performed using affinity purified goat antimouse immunoglobulins specific for IgG heavy chains and ..mu..(IgM). All antibodies were IgM as evidenced by 40 times greater than background activity when 25,000 cpm of /sup 125/I-labelled goat anti-mouse IgM was used as second antibody in a radioimmunoassay.

  6. Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.

    PubMed Central

    Scoble, J E; Mills, S; Hruska, K A

    1985-01-01

    The effects of parathyroid hormone were studied on Ca2+ fluxes in canine renal proximal tubular basolateral membrane vesicles (BLMV). Efflux of Ca2+ from preloaded BLMV was found to be stimulated by an external Na+ gradient, and this was inhibited by the Na+ ionophore, monensin, and enhanced by intravesicular negative electrical potentials, which indicated electrogenic Na+/Ca2+ exchange activity. There was a Na+ gradient independent Ca2+ flux, but membrane binding of Ca2+ was excluded from contributing to the Na+ gradient-dependent efflux. The Na+ gradient-dependent flux of Ca2+ was very rapid, and even 2- and 5-s points may not fully represent absolute initial rates. It was saturable with respect to the interaction of Ca2+ and Na+ with an apparent (5 s) Km for Na+-dependent Ca2+ uptake of 10 microM, and an apparent (5 s) Vmax of 0.33 nmol/mg protein per 5 s. The Na+ concentration that yielded half maximal Ca2+ efflux (2 s) was 11 mM, and the Hill coefficient was two or greater. Both Na+ gradient dependent and independent Ca2+ efflux were decreased in BLMV prepared from kidneys of thyroparathyroidectomized (TPTX) dogs, and both were stimulated by parathyroid hormone (PTH) infusion to TPTX dogs. BLMV from TPTX dogs exhibited significantly reduced maximal stimulation of Na+ gradient-dependent Ca2+ uptake with an apparent (5 s) Vmax of 0.23 nmol/mg protein per 5 s, but the apparent Km was 8 microM, which was unchanged from normal. The Na+ gradient independent Ca2+ uptake was also reduced in BLMV from TPTX dogs compared with normal. Thus, PTH stimulated both Na+/Ca2+ exchange activity and Na+ independent Ca2+ flux. In vivo, the latter could result in an elevation of cytosolic Ca2+ by PTH, and this might contribute to the observed decrease in solute transport in the proximal tubule. Images PMID:3988932

  7. Characterization of soluble and particulate parathyroid hormone receptors using a biotinylated bioactive hormone analog.

    PubMed

    Brennan, D P; Levine, M A

    1987-10-25

    A bioactive biotin-containing derivative of the synthetic bovine parathyroid hormone analog [Nle8,Nle18,Tyr34]bovine parathyroid hormone-(1-34) (bPTH-(1-34] amide was prepared by reacting the peptide with N-biotinyl-epsilon-aminocaproic acid N-hydroxysuccinimide ester. The derivative was incubated with particulate renal plasma membranes or with detergent [3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) extracts of renal cortical membranes, and two membrane components were identified. Labeling of these components was competitively inhibited by underivatized bPTH-(1-34) or bPTH-(3-34) but not by insulin, adrenocorticotropin, or oxidized rat PTH-(1-34). PTH-binding components that were immobilized on nitrocellulose could be detected by incubating the membrane with biotinyl-bPTH-(1-34). Binding components of apparent molecular mass 68, 70, and 150 kDa were specifically labeled in plasma membranes derived from canine, human, and porcine renal cortex, rat liver, and human fibroblasts. The 68-kDa binding protein was found to be consistently more acidic than the 70-kDa binding protein in human, porcine, and canine renal membranes analyzed by two-dimensional electrophoresis. The 68-70-kDa receptor doublet could be specifically isolated by streptavidin-agarose chromatography of solubilized membrane extracts that had first been incubated with biotinyl-BPTH-(1-34). Biotinyl-bPTH-(1-34) should be useful as a tool for further characterization and purification of the PTH receptor. PMID:2822699

  8. Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling.

    PubMed

    McGarvey, Jennifer C; Xiao, Kunhong; Bowman, Shanna L; Mamonova, Tatyana; Zhang, Qiangmin; Bisello, Alessandro; Sneddon, W Bruce; Ardura, Juan A; Jean-Alphonse, Frederic; Vilardaga, Jean-Pierre; Puthenveedu, Manojkumar A; Friedman, Peter A

    2016-05-20

    The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domain-containing proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor. PMID:27008860

  9. Influence of Vitamin D and Parathyroid Hormone on Bone and Metabolic Risk in Women with Previous Gestational Diabetes

    PubMed Central

    Serra, Monica C.; Ryan, Alice S.

    2016-01-01

    The purpose of this study was to compare plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH), VO2max, bone (by DXA), and metabolic outcomes across age and race-matched postmenopausal women (54±1 years; mean±SEM): 1) with previous gestational diabetes (GDM) (32±1 kg/m2; N=17), 2) without previous GDM, but with a similar BMI to GDM (32±1 kg/m2; N=17), and 3) without previous GDM, but with a higher BMI than GDM (36±1 kg/m2; N=17; P<0.01). The prevalence of 25(OH)D insufficiency and deficiency was high (~80%), but not different across groups, while PTH tended to be ~30% lower in women with a history of GDM (P=0.09). Women with a history of GDM had lower HDL cholesterol and higher diastolic blood pressure and fasting and 2-hr glucose levels (by oral glucose tolerance test) (vs. groups 2 and 3; P’s<0.05). Bone mineral density (BMD) tended to be slightly higher in women with prior GDM than the BMI matched women with no prior GDM (P=0.09). Overall, higher PTH was associated with lower femoral neck (r=−0.33) and (r=−0.38) (P’s<0.05), while lower 25(OH)D was associated with lower VO2max (r=0.25, P=0.05) and higher fasting glucose (r=−0.14) and insulin (r=−0.29 (P’s<0.05). We observe that the poor metabolic profiles of postmenopausal women with a history of GDM are independent of 25(OH)D and PTH. However, due to associations between 25(OH)D and PTH with bone and metabolic outcomes, maintaining recommended 25(OH)D and PTH concentrations is important regardless of a previous history of GDM. PMID:26882050

  10. Computer program for analysis of parathyroid scintigraphy examinations: combination of dual-tracer (subtraction) and double phase single-tracer washout techniques.

    PubMed

    Kobylecka, Małgorzata Iwona; Bajera, Adam; Fronczewska-Wieniawska, Katarzyna; Mączewska, Joanna; Płazińska, Maria Teresa; Królicki, Leszek

    2016-01-01

    There is no controversy in the published literature that sensitivity and specificity of parathyroid scintigraphy is superior to other imaging techniques. However no uniform protocol has been established for scintigraphy. In order to analyze parathyroid scintigraphic images in the Department of Nuclear Medicine at the Medical University of Warsaw we have developed a program that allows qualitative and quantitative evaluation of recorded images and motion artifacts correction. This program offers a uniform procedure of analysis of parathyroid imaging results in diagnostic centers, accelerates the analysis of parathyroid tests performed with use of single radioactive tracer, that require the acquisition of consecutive images of the patient, without altering his body position between successive stages of registration. This program allows for automation of previously time consuming procedures and thus saves time and decreases a risk of operator's errors. PMID:26838947

  11. Root-Associated Methane Oxidation and Methanogenesis: Key Determinants of Wetland Methane Emissions

    NASA Technical Reports Server (NTRS)

    King, G. M.

    1997-01-01

    During the award period, we have assessed the extent and controls of methane oxidation in north temperate wetlands. It is evident that wetlands have been a major global source of atmospheric methane in the past, and are so at present. It is also evident that microbial methane oxidation consumes a variable fraction of total wetland methane production, perhaps 10%-90%. Methane oxidation is thus a potentially important control of wetland methane emission. Our efforts have been designed to determine the extent of the process, its controls, and possible relationships to changes that might be expected in wetlands as a consequence of anthropogenic or climate-related disturbances. Current work, has emphasized controls of methane oxidation associated with rooted aquatic plants. As for the sediment-water interface, we have observed that oxygen availability is a primary limiting factor. Our conclusion is based on several different lines of evidence obtained from in vitro and in situ analyses. First, we have measured the kinetics of methane oxidation by intact plant roots harboring methane-oxidizing bacteria, as well as the kinetics of the methanotrophs themselves. Values for the half-saturation constant (apparent K(sub m)) are approximately 5 microns. These values are roughly equivalent to, or much less than porewater methane concentrations, indicating that uptake is likely saturated with respect to methane, and that some other parameter must limit activity. Methane concentrations in the lacunar spaces at the base of plant stems are also comparable to the half-saturation constants (when expressed as equivalent dissolved concentrations), providing further support for limitation of uptake by parameters other than methane.

  12. Cropping systems and cultural practices determine the Rhizoctonia anastomosis groups associated with Brassica spp. in Vietnam.

    PubMed

    Hua, Gia Khuong Hoang; Bertier, Lien; Soltaninejad, Saman; Höfte, Monica

    2014-01-01

    Ninety seven Rhizoctonia isolates were collected from different Brassica species with typical Rhizoctonia symptoms in different provinces of Vietnam. The isolates were identified using staining of nuclei and sequencing of the rDNA-ITS barcoding gene. The majority of the isolates were multinucleate R. solani and four isolates were binucleate Rhizoctonia belonging to anastomosis groups (AGs) AG-A and a new subgroup of A-F that we introduce here as AG-Fc on the basis of differences in rDNA-ITS sequence. The most prevalent multinucleate AG was AG 1-IA (45.4% of isolates), followed by AG 1-ID (17.5%), AG 1-IB (13.4%), AG 4-HGI (12.4%), AG 2-2 (5.2%), AG 7 (1.0%) and an unknown AG related to AG 1-IA and AG 1-IE that we introduce here as AG 1-IG (1.0%) on the basis of differences in rDNA-ITS sequence. AG 1-IA and AG 1-ID have not been reported before on Brassica spp. Pathogenicity tests revealed that isolates from all AGs, except AG-A, induced symptoms on detached leaves of several cabbage species. In in vitro tests on white cabbage and Chinese cabbage, both hosts were severely infected by AG 1-IB, AG 2-2, AG 4-HGI, AG 1-IG and AG-Fc isolates, while under greenhouse conditions, only AG 4-HGI, AG 2-2 and AG-Fc isolates could cause severe disease symptoms. The occurrence of the different AGs seems to be correlated with the cropping systems and cultural practices in different sampling areas suggesting that agricultural practices determine the AGs associated with Brassica plants in Vietnam. PMID:25372406

  13. Cropping Systems and Cultural Practices Determine the Rhizoctonia Anastomosis Groups Associated with Brassica spp. in Vietnam

    PubMed Central

    Soltaninejad, Saman; Höfte, Monica

    2014-01-01

    Ninety seven Rhizoctonia isolates were collected from different Brassica species with typical Rhizoctonia symptoms in different provinces of Vietnam. The isolates were identified using staining of nuclei and sequencing of the rDNA-ITS barcoding gene. The majority of the isolates were multinucleate R. solani and four isolates were binucleate Rhizoctonia belonging to anastomosis groups (AGs) AG-A and a new subgroup of A-F that we introduce here as AG-Fc on the basis of differences in rDNA-ITS sequence. The most prevalent multinucleate AG was AG 1-IA (45.4% of isolates), followed by AG 1-ID (17.5%), AG 1-IB (13.4%), AG 4-HGI (12.4%), AG 2-2 (5.2%), AG 7 (1.0%) and an unknown AG related to AG 1-IA and AG 1-IE that we introduce here as AG 1-IG (1.0%) on the basis of differences in rDNA-ITS sequence. AG 1-IA and AG 1-ID have not been reported before on Brassica spp. Pathogenicity tests revealed that isolates from all AGs, except AG-A, induced symptoms on detached leaves of several cabbage species. In in vitro tests on white cabbage and Chinese cabbage, both hosts were severely infected by AG 1-IB, AG 2-2, AG 4-HGI, AG 1-IG and AG-Fc isolates, while under greenhouse conditions, only AG 4-HGI, AG 2-2 and AG-Fc isolates could cause severe disease symptoms. The occurrence of the different AGs seems to be correlated with the cropping systems and cultural practices in different sampling areas suggesting that agricultural practices determine the AGs associated with Brassica plants in Vietnam. PMID:25372406

  14. Faecal Microbiota Composition in Adults Is Associated with the FUT2 Gene Determining the Secretor Status

    PubMed Central

    Wacklin, Pirjo; Tuimala, Jarno; Nikkilä, Janne; Sebastian Tims; Mäkivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Mättö, Jaana

    2014-01-01

    The human intestine is colonised with highly diverse and individually defined microbiota, which likely has an impact on the host well-being. Drivers of the individual variation in the microbiota compositions are multifactorial and include environmental, host and dietary factors. We studied the impact of the host secretor status, encoded by fucosyltransferase 2 (FUT2) -gene, on the intestinal microbiota composition. Secretor status determines the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucosa. The study population was comprised of 14 non-secretor (FUT2 rs601338 genotype AA) and 57 secretor (genotypes GG and AG) adult individuals of western European descent. Intestinal microbiota was analyzed by PCR-DGGE and for a subset of 12 non-secretor subjects and 12 secretor subjects additionally by the 16S rRNA gene pyrosequencing and the HITChip phylogenetic microarray analysis. All three methods showed distinct clustering of the intestinal microbiota and significant differences in abundances of several taxa representing dominant microbiota between the non-secretors and the secretors as well as between the FUT2 genotypes. In addition, the non-secretors had lower species richness than the secretors. The soft clustering of microbiota into enterotypes (ET) 1 and 3 showed that the non-secretors had a higher probability of belonging to ET1 and the secretors to ET3. Our study shows that secretor status and FUT2 polymorphism are associated with the composition of human intestinal microbiota, and appears thus to be one of the key drivers affecting the individual variation of human intestinal microbiota. PMID:24733310

  15. Sources and magnitude of bias associated with determination of polychlorinated biphenyls in environmental samples

    USGS Publications Warehouse

    Eganhouse, R.P.; Gossett, R.W.

    1991-01-01

    Recently complled data on the composition of commercial Aroclor mixtures and ECD (electron capture detector) response factors for all 209 PCB congeners are used to develop estimates of the bias associated with determination of polychlorinated blphenyis. During quantitation of multlcomponent peaks by congener-specific procedures error is introduced because of variable ECD response to isomeric PCBs. Under worst case conditions, the magnitude of this bias can range from less than 2% to as much as 600%. Multicomponent peaks containing the more highly and the lower chlorinated congeners experience the most bias. For this reason, quantitation of ??PCB in Aroclor mixtures dominated by these species (e.g. 1016) are potentially subject to the greatest error. Comparison of response factor data for ECDs from two laboratories shows that the sign and magnitude of calibration bias for a given multicomponent peak is variable and depends, in part, on the response characteristics of individual detectors. By using the most abundant congener (of each multicomponent peak) for purposes of calibration, one can reduce the maximum bias to less than 55%. Moreover, due to cancellation of errors, the bias resulting from summation of all peak concentrations (i.e. ??PCB) becomes vanishingly small (200%) and highly variable in sign and magnitude. In this case, bias originates not only from the incomplete chromatographic resolution of PCB congeners but also the overlapping patterns of the Aroclor mixtures. Together these results illustrate the advantages of the congener-specific method of PCB quantitation over the traditional Aroclor Method and the extreme difficulty of estimating bias incurred by the latter procedure on a post hoc basis.

  16. Structural Basis for Parathyroid Hormone-related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-selective Peptides

    SciTech Connect

    Pioszak, Augen A.; Parker, Naomi R.; Gardella, Thomas J.; Xu, H. Eric

    2009-12-01

    Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic {alpha}-helix to the same hydrophobic groove in the ECD as occupied by PTH, but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally 'unwound.' The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.

  17. Nucleotide sequence analysis of CDR3 elements of a panel of anti-peptide monoclonal antibodies recognizing parathyroid hormone-related protein.

    PubMed Central

    Rapley, R; Flora, P S; Walsh, D J; Walker, M R

    1993-01-01

    Nucleotide sequences of heavy (VH) and light (VL) chain variable region complementarity determining regions have been determined from in vitro amplified mRNA isolated from a panel of monoclonal antibodies (mAb) raised to a synthetic 34mer peptide representing the N-terminal portion of human parathyroid hormone-related protein (PTHrP or parathyrin) reported to contain an immunodominant epitope. These mAb vary in affinity for the synthetic peptide and native PTHrP (Ka between 5.9 x 10(8) and 1.9 x 10(11)l/M). All 10 mAb studied were found were found to utilized restricted VH2, V kappa 2, JH4 and J kappa 1 family genes. Significant differences in the length and sequence of D elements were found; however 9/10 mAb utilize members of the DSP2 family. Significantly, two broad ranges of affinity could be determined based on the presence of Asp or Ala at residue 101 in JH. Images Figure 2 PMID:8478021

  18. Parathyroid hormone is a plausible mediator for the metabolic syndrome in the morbidly obese: a cross-sectional study

    PubMed Central

    2011-01-01

    Background The biological mechanisms in the association between the metabolic syndrome (MS) and various biomarkers, such as 25-hydroxyvitamin D (vit D) and magnesium, are not fully understood. Several of the proposed predictors of MS are also possible predictors of parathyroid hormone (PTH). We aimed to explore whether PTH is a possible mediator between MS and various possible explanatory variables in morbidly obese patients. Methods Fasting serum levels of PTH, vit D and magnesium were assessed in a cross-sectional study of 1,017 consecutive morbidly obese patients (68% women). Dependencies between MS and a total of seven possible explanatory variables as suggested in the literature, including PTH, vit D and magnesium, were specified in a path diagram, including both direct and indirect effects. Possible gender differences were also included. Effects were estimated using Bayesian path analysis, a multivariable regression technique, and expressed using standardized regression coefficients. Results Sixty-eight percent of the patients had MS. In addition to type 2 diabetes and age, both PTH and serum phosphate had significant direct effects on MS; 0.36 (95% Credibility Interval (CrI) [0.15, 0.57]) and 0.28 (95% CrI [0.10,0.47]), respectively. However, due to significant gender differences, an increase in either PTH or phosphate corresponded to an increased OR for MS in women only. All proposed predictors of MS had significant direct effects on PTH, with vit D and phosphate the strongest; -0.27 (95% CrI [-0.33,-0.21]) and -0.26 (95% CrI [-0.32,-0.20]), respectively. Though neither vit D nor magnesium had significant direct effects on MS, for women they both affected MS indirectly, due to the strong direct effect of PTH on MS. For phosphate, the indirect effect on MS, mediated through serum calcium and PTH, had opposite sign than the direct effect, resulting in the total effect on MS being somewhat attenuated compared to the direct effect only. Conclusion Our results

  19. Utility of 18F-choline photon emission tomography/computed tomography in the diagnosis of parathyroid adenoma

    PubMed Central

    Damle, Nishikant Avinash; Tripathi, Madhavi; Behera, Abhishek; Aggarwal, Sameer; Bal, Chandrasekhar; Aggarwal, Shipra; Aggarwal, Vivek; Kandasamy, Devasenathipathi; Taywade, Sameer

    2016-01-01

    Recently, the role of 18F-choline in the detection of parathyroid adenomas has been reported. At our institution, we are currently studying the role of this tracer in comparison to the standard methoxy-isobutyl-isonitrile.(MIBI) scan with single photon emission tomography/computed tomography. Our initial results show that 18F-choline is at least as good as 99mTc-MIBI scan. We present here a representative case of a 45-year-old woman with multiple skeletal lytic lesions and a high parathyroid hormone.(PTH) who underwent both these imaging techniques with concordant results, further confirmed by histopathology and postoperative fall in serum PTH levels. PMID:27385893

  20. Utility of (18)F-choline photon emission tomography/computed tomography in the diagnosis of parathyroid adenoma.

    PubMed

    Damle, Nishikant Avinash; Tripathi, Madhavi; Behera, Abhishek; Aggarwal, Sameer; Bal, Chandrasekhar; Aggarwal, Shipra; Aggarwal, Vivek; Kandasamy, Devasenathipathi; Taywade, Sameer

    2016-01-01

    Recently, the role of (18)F-choline in the detection of parathyroid adenomas has been reported. At our institution, we are currently studying the role of this tracer in comparison to the standard methoxy-isobutyl-isonitrile.(MIBI) scan with single photon emission tomography/computed tomography. Our initial results show that (18)F-choline is at least as good as 99mTc-MIBI scan. We present here a representative case of a 45-year-old woman with multiple skeletal lytic lesions and a high parathyroid hormone.(PTH) who underwent both these imaging techniques with concordant results, further confirmed by histopathology and postoperative fall in serum PTH levels. PMID:27385893

  1. What determines the strength of noncovalent association of ligands to proteins in aqueous solution?

    PubMed Central

    Miyamoto, S; Kollman, P A

    1993-01-01

    Free energy perturbation methods using molecular dynamics have been used to calculate the absolute free energy of association of two ligand-protein complexes. The calculations reproduce the significantly more negative free energy of association of biotin to streptavidin, compared to N-L-acetyltryptophanamide/alpha-chymotrypsin. This difference in free energy of association is due to van der Waals/dispersion effects in the nearly ideally performed cavity that streptavidin presents to biotin, which involves four tryptophan residues. Images Fig. 2 PMID:8378312

  2. EVALUATION OF THE FOURIER TRANSFORM INFRARED SPECTROMETER FOR PARTICLE-ASSOCIATED AMMONIUM SULFATE DETERMINATION

    EPA Science Inventory

    A commercial Fourier transform infrared (FTIR) spectrometer, modified for automated analysis of particulate-associated sulfate, was used to obtain transmission spectra samples of particulate matter collected from the ambient air onto Teflon filters. n evaluation of this instrumen...

  3. Direct Versus Indirect Determination Of Suspended Sediment Associated Metals In A Mining-Influenced Watershed

    EPA Science Inventory

    The differentiation between the concentration of metals associated with suspended sediments and those in the dissolved phase is often of importance in aquatic ecosystems, for such reasons as toxicity evaluation, total maximum daily load calculations, and a better understanding of...

  4. EVALUATION OF THREE CLEANING METHODS FOR REMOVING ASBESTOS FROM CARPET: DETERMINATION OF AIRBORNE ASBESTOS CONCENTRATIONS ASSOCIATED WITH EACH METHOD

    EPA Science Inventory

    This study was conducted to compare the effectiveness of three cleaning methods to remove asbestos from contaminated carpet and to determine the airborne asbestos concentrations associated with the use of each method. he carpet on which the methods were tested was naturally conta...

  5. EVALUATION OF THREE CLEANING METHODS FOR REMOVING ASBESTOS FROM CARPET. DETERMINATION OF AIRBORNE ASBESTOS CONCENTRATIONS ASSOCIATED WITH EACH METHOD

    EPA Science Inventory

    This study was conducted to compare the effectiveness of three cleaning methods to remove asbestos from contaminated carpet and to determine the airborne asbestos concentrations associated with the use of each method. The carpet on which the methods were tested was naturally cont...

  6. Understanding the Association between Future Time Perspective and Self-Regulated Learning through the Lens of Self-Determination Theory

    ERIC Educational Resources Information Center

    de Bilde, Jerissa; Vansteenkiste, Maarten; Lens, Willy

    2011-01-01

    The present cross-sectional research examined a process underlying the positive association between holding an extended future time perspective (FTP) and learning outcomes through the lens of self-determination theory. High school students and university students (N = 275) participated in the study. It was found that students with an extended FTP…

  7. The effect of cellulose phosphate on plasma and urinary magnesium at different levels of parathyroid function in man.

    PubMed

    Parfitt, A M

    1976-08-01

    1. Previously published data obtained by magnesium infusion in man were found to conform to a Tm/glomerular filtration rate (GFR) model on the assumption of 80% diffusibility of plasma magnesium. The lower limit of Tm,Mg/GFR was 625 mumol/l. 2. Previously published data concerning the effect of cellulose phosphate on magnesium metabolism in normal subjects, patients with latent hypoparathyroidism and patients with primary hyperparathyroidism were found to conform to the same model, with the same limit for Tm,Mg/GFR for all three levels of parathyroid function. 3. The threshold for magnesium excretion is sharper with less 'splay' than for phosphate, but as for phosophate it is close to the normal blood concentration. 4. Because of the geometrical relationship between different methods of presentation of data, at a constant value for Tm,Mg/GFR changes in magnesium load or in GFR automatically produce changes in fractional magnesium clearance. This is the explanation for the increase in fractional magnesium clearance which occurs which with diminishing renal function. 5. Renal conservation of magnesium is a passive consequence of the fall in plasma magnesium. There was no evidence of augmented tubular reabsorption of magnesium in response to magnesium deprivation in any of the three groups of subjects. 6. The tubular reabsorption of magnesium was not altered detectably by a moderate deficiency or excess of parathyroid hormore. Changes in parathyroid hormone secretion are probably not concerned in normal magnesium homeostasis. PMID:954362

  8. Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99mTc sestamibi SPECT and SPECT/CT.

    PubMed

    Eslamy, Hedieh K; Ziessman, Harvey A

    2008-01-01

    The clinical diagnosis of primary hyperparathyroidism is based largely on serum laboratory test results, as patients often are asymptomatic. Surgery, often with bilateral exploration of the neck, has been considered the definitive treatment for symptomatic disease. However, given that approximately 90% of cases are due to a single parathyroid adenoma, a better treatment may be the selective surgical excision of the hyperfunctioning parathyroid gland after its preoperative identification and localization at radiologic imaging. Scintigraphy and ultrasonography are the imaging modalities most often used for preoperative localization. Various scintigraphic protocols may be used in the clinical setting: Single-phase dual-isotope subtraction imaging, dual-phase single-isotope imaging, or a combination of the two may be used to obtain planar or tomographic views. Single photon emission computed tomography (SPECT) with the use of technetium-99m ((99m)Tc) sestamibi as the radiotracer, especially when combined with x-ray-based computed tomography (CT), is particularly helpful for preoperative localization: The three-dimensional functional information from SPECT is fused with the anatomic information obtained from CT. In addition, knowledge of the anatomy and embryologic development of the parathyroid glands and the pathophysiology of primary hyperparathyroidism aid in the identification and localization of hyperfunctioning glands. PMID:18794320

  9. Binding of ( sup 125 I)iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    SciTech Connect

    Jones, J.I.; Fitzpatrick, L.A. )

    1990-04-01

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with (125I) iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for (125I) iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited (125I) iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes.

  10. Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Jerome, C P; Johnson, C S; Vafai, H T; Kaplan, K C; Bailey, J; Capwell, B; Fraser, F; Hansen, L; Ramsay, H; Shadoan, M; Lees, C J; Thomsen, J S; Mosekilde, L

    1999-09-01

    A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 microg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck

  11. Individual and combined effects of noise-like whole-body vibration and parathyroid hormone treatment on bone defect repair in ovariectomized mice.

    PubMed

    Matsumoto, Takeshi; Sato, Daisuke; Hashimoto, Yoshihiro

    2016-01-01

    The effectiveness of intermittent administration of parathyroid hormone and exposure to whole-body vibration on osteoporotic fracture healing has been previously investigated, but data on their concurrent use are lacking. Thus, we evaluated the effects of intermittent administration of parathyroid hormone, whole-body vibration, and their combination on bone repair in osteoporotic mice. Noise-like whole-body vibration with a broad frequency range was used instead of conventional sine-wave whole-body vibration at a specific frequency. Mice were ovariectomized at 9 weeks of age and subjected to drill-hole surgery in the right tibial diaphysis at 11 weeks. The animals were divided into four groups (n = 12 each): a control group, and groups treated with intermittent administration of parathyroid hormone, noise-like whole-body vibration, and both. From postoperative day 2, the groups treated with intermittent administration of parathyroid hormone and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were subcutaneously administered parathyroid hormone at a dose of 30 µg/kg/day. The groups treated with noise-like whole-body vibration and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were exposed to noise-like whole-body vibration at a root mean squared acceleration of 0.3g and frequency components of 45-100 Hz for 20 min/day. Following 18 days of interventions, the right tibiae were harvested, and the regenerated bone was analyzed by micro-computed tomography and nanoindentation testing. Compared with the control group, callus volume fraction was 40% higher in groups treated with intermittent administration of parathyroid hormone and 73% higher in groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration, and callus thickness was 35% wider in groups treated with both

  12. Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase.

    PubMed

    Larsson, Sara; Jones, Helena A; Göransson, Olga; Degerman, Eva; Holm, Cecilia

    2016-03-01

    Parathyroid hormone (PTH) is secreted from the parathyroid glands in response to low plasma calcium levels. Besides its classical actions on bone and kidney, PTH may have other important effects, including metabolic effects, as suggested for instance by increased prevalence of insulin resistance and type 2 diabetes in patients with primary hyperparathyroidism. Moreover, secondary hyperparathyroidism may contribute to the metabolic derangements that characterize states of vitamin D deficiency. PTH has been shown to induce adipose tissue lipolysis, but the details of the lipolytic action of PTH have not been described. Here we used primary mouse adipocytes to show that intact PTH (1-84) as well as the N-terminal fragment (1-37) acutely stimulated lipolysis in a dose-dependent manner, whereas the C-terminal fragment (38-84) was without lipolytic effect. The lipolytic action of PTH was paralleled by phosphorylation of known protein kinase A (PKA) substrates, i.e. hormone-sensitive lipase (HSL) and perilipin. The phosphorylation of HSL in response to PTH occurred at the known PKA sites S563 and S660, but not at the non-PKA site S565. PTH-induced lipolysis, as well as phosphorylation of HSL at S563 and S660, was blocked by both the PKA-inhibitor H89 and the adenylate cyclase inhibitor MDL-12330A, whereas inhibitors of extracellular-regulated kinase (ERK), protein kinase B (PKB), AMP-activated protein kinase (AMPK) and Ca(2+)/calmodulin-dependent protein kinase (CaMK) had little or no effect. Inhibition of phosphodiesterase 4 (PDE4) strongly potentiated the lipolytic action of PTH, whereas inhibition of PDE3 had no effect. Our results show that the lipolytic action of PTH is mediated by the PKA signaling pathway with no or minor contribution of other signaling pathways and, furthermore, that the lipolytic action of PTH is limited by simultaneous activation of PDE4. Knowledge of the signaling pathways involved in the lipolytic action of PTH is important for our

  13. Disruption of parathyroid hormone and parathyroid hormone-related peptide receptor phosphorylation prolongs ERK1/2 MAPK activation and enhances c-fos expression

    PubMed Central

    Abou-Samra, Abdul B.

    2012-01-01

    Previous studies have demonstrated that parathyroid hormone (PTH) binding to the PTH/PTH-related peptide receptor (PPR) stimulates G protein coupling, receptor phosphorylation, β-arrestin translocation, and internalization of the ligand/receptor complex. The extracellular signal-regulated mitogen-activated protein kinases 1/2 (ERK1/2 MAPK) are downstream effectors of PPR. In the current study, we investigated the role of PPR phosphorylation in the PTH regulation of the ERK1/2 MAPK pathway. Short treatment with PTH (0–40 min) of LLCP-K1 cells stably expressing a wild-type (WT) or a phosphorylation-deficient (PD) PPR (WT-PPR or PD-PPR cells, respectively) results in similar activation of ERK1/2. Interestingly, PTH stimulation of ERK1/2 in the WT-PPR cells then decreases as a result of longer PTH (60 min) treatment, and inhibition of ERK1/2 by PTH is observed at 90 min. Strikingly, the PD-PPR cells exhibit prolonged ERK1/2 activation up to 90 min of PTH treatment. An ERK1/2-dependent increase in c-fos expression is observed in the PD-PPR cells. Subsequently, c-fos expression in the WT-PPR and PD-PPR cells was markedly attenuated by a specific ERK1/2 pathway inhibitor. Further investigations revealed that PTH treatment causes a robust recruitment of a green fluorescent protein-tagged β-arrestin2 (β-arrestin2-GFP) in the WT-PPR cells. In contrast, β-arrestin2 recruitment was reduced in the PD-PPR cells. Importantly, expression of a receptor phosphorylation-independent β-arrestin2 (R169E) in the PD-PPR cells restored the biphasic effect of PTH on ERK1/2 as in the WT-PPR cells. The study reports a novel role for receptor phosphorylation and β-arrestin2 in the subsequent inhibition of the ERK1/2 pathway and in control of gene expression. PMID:22414806

  14. Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Jee, W. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

    1995-01-01

    The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone

  15. Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Jee, W. S. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

    1994-01-01

    The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates

  16. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    PubMed

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  17. Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

    PubMed

    Koster, Roelof; Mitra, Nandita; D'Andrea, Kurt; Vardhanabhuti, Saran; Chung, Charles C; Wang, Zhaoming; Loren Erickson, R; Vaughn, David J; Litchfield, Kevin; Rahman, Nazneen; Greene, Mark H; McGlynn, Katherine A; Turnbull, Clare; Chanock, Stephen J; Nathanson, Katherine L; Kanetsky, Peter A

    2014-11-15

    Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT. PMID:24943593

  18. 77 FR 35427 - Certain Mobile Devices, Associated Software, and Components Thereof Final Determination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... (``Microsoft''). 75 FR 68379-80 (Nov. 5, 2010). The complaint alleges violations of section 337 of the Tariff... portions of the final ID and issued a Notice to that effect dated March 2, 2012. 77 FR 14043 (Mar. 8, 2012... from non-parties Association for Competitive Technology, Inc. and Google Inc. On review, the...

  19. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis

    EPA Science Inventory

    ABSTRACT BACKGROUND Anti-neutrophil cytoplasmic autoantibodies (ANCA) specific for myeloperoxidase (MPO) or proteinase 3 (PR3) are detectable in >90% of patients with ANCA-associated vasculitis (AAV). ANCA titers do not correlate well with disease activity. In vivo and in vi...

  20. Determination of structural requirements and probable regulatory effectors for membrane association of maize sucrose synthase 1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sucrose synthase (SUS) cleaves sucrose to form UDP-glucose and fructose, and exists in soluble (s-SUS) and membrane-associated (m-SUS) forms, with the latter proposed to channel UDP-glucose to the cellulose synthase complex on the plasma membrane of plant cells during synthesis of cellulose. However...

  1. Flow cytometric determination of leukemia-associated marker combinations for the study of minimal residual disease.

    PubMed

    Babusíková, O; Glasová, M; Kusenda, J; Koníková, E; Mésárosová, A

    1994-01-01

    To study the minimal residual disease in acute leukemia patients we used some marker combinations related either to the simultaneous surface membrane and cytoplasmic marker expression, or to the expression of atypical marker combinations, that are absent or extremely rare in normal hematopoietic cells. We investigated to which extent flow cytometric analysis of leukemia-associated marker combination may contribute to sensitive follow-up in patients with acute leukemia. For this purpose dilution experiments were performed, in which artificial mixtures of normal peripheral blood lymphocytes and leukemia cells from a patient with leukemia-associated phenotype were prepared and analyzed for double positive cells. Our results showed that the sensitivity of double color immunofluorescence assay was 3 in 10(4) cells. Sequential studies of residual disease were evaluated in five acute leukemia patients with leukemia-associated markers combinations at diagnosis. In three of them morphologic relapse was preceded by the immunologic detection of small amounts of leukemia cells, while in two other cases, in which no double positive cells for leukemia-associated markers were found, patients are still in hematologic remission. This approach to the study of minimal residual disease could be valuable in monitoring the efficiency of chemotherapy, as well as in evaluating the quality control of bone marrow before autografting. Furthermore, flow cytometric approach can efficiently complete other methods, which are used for more exact definition of remission in acute leukemia patients. PMID:7870213

  2. Causal association of electromagnetic signals using the Cayley-Menger determinant

    NASA Astrophysics Data System (ADS)

    Drake, Samuel Picton; Anderson, Brian D. O.; Yu, Changbin

    2009-07-01

    In complex electromagnetic environments it can often be difficult to determine whether signals received by an antenna array emanated from the same source. The failure to appropriately assign signal reception events to the correct emission event makes accurate localization of the signal source impossible. In this paper we show that as the received signal events must lie on the light-cone of the emission event the Cayley-Menger determinate calculated from using the light-cone geodesic distances between received signals must be zero. This result enables us to construct an algorithm for sorting received signals into groups corresponding to the same far-field emission.

  3. NO1: an HLA-DQw1-associated determinant present on loss mutants not expressing DQw1.

    PubMed

    Ohta, N; Bach, F H

    1986-05-01

    We have used two monoclonal antibodies, FA and Tu39, and cloned cytotoxic T lymphocytes to study the immunogenetic control of an HLA-D region-encoded determinant(s) recognized by the Tc other than class I or DR or DQ. The Tc recognize a determinant associated with one (the A2) haplotype of LCL721 and are lytic to mutants of LCL 721 that have lost expression of all class I as well as the serologically defined DR and DQw specificities associated with, and presumably identical to, DPw2, the specificity encoded by the sensitizing (A2-B51) haplotype; these data provide the first evidence that FA recognizes the protein dimer presumably expressing the DPw determinant. Those Tc blocked by Tu39 recognized a determinant, referred to as NO1, that is not associated in the population with DPw2, but is found on some, but not all, DQw1-positive cells. We propose three possible explanations for these results. (i) There may be a class II product other than DP or those expressing the DR or DQ serologically defined specificities carrying NO1; such a product could be either as yet undescribed (E. Long has obtained information for an expressed and as yet undefined class II beta gene, personal communication) or a second expressed dimer of the DQ or DP families. (We assume that no DR genes of the A2 haplotype are expressed in these mutants. (ii) NO1 and DPw2 may be on the same molecule; to account for the lack of association of NO1 and DPw2 in the population, one might propose a mechanism such as gene conversion leading to expression of NO1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2423488

  4. Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism.

    PubMed

    Alexander, H Richard; Chen, Clara C; Shawker, Thomas; Choyke, Peter; Chan, Teresa J; Chang, Richard; Marx, Stephen J

    2002-11-01

    Patients with recurrent or persistent primary hyperparathyroidism have increased operative risk because of scarring in the operative field and the frequent presence of an ectopic gland. Preoperative imaging studies will identify the hyperfunctioning parathyroid gland in the majority of circumstances. The best types or combination of imaging tests has not been definitely established. However, because of their wide availability and demonstrated sensitivity, US and sestamibi scans are most commonly obtained. Based on the clinical setting, additional tests including CT or MRI may be useful. In circumstances when the noninvasive imaging modalities are inconclusive, invasive imaging tests including selective angiography venous sampling and/or direct fine needle aspiration should be used. IOUS, MIRP, and intraoperative PTH determination are useful adjuncts to the safe and successful conduct of reoperative parathyroid surgery: however, the benefit of the routine use of these modalities in reoperative parathyroid surgery has yet to be critically determined. PMID:12412790

  5. Experimental determination of the particle motions associated with the low order acoustic modes in enclosures

    NASA Technical Reports Server (NTRS)

    Byrne, K. P.; Marshall, S. E.

    1983-01-01

    A procedure for experimentally determining, in terms of the particle motions, the shapes of the low order acoustic modes in enclosures is described. The procedure is based on finding differentiable functions which approximate the shape functions of the low order acoustic modes when these modes are defined in terms of the acoustic pressure. The differentiable approximating functions are formed from polynomials which are fitted by a least squares procedure to experimentally determined values which define the shapes of the low order acoustic modes in terms of the acoustic pressure. These experimentally determined values are found by a conventional technique in which the transfer functions, which relate the acoustic pressures at an array of points in the enclosure to the volume velocity of a fixed point source, are measured. The gradient of the function which approximates the shape of a particular mode in terms of the acoustic pressure is evaluated to give the mode shape in terms of the particle motion. The procedure was tested by using it to experimentally determine the shapes of the low order acoustic modes in a small rectangular enclosure.

  6. 76 FR 78090 - Guidance on Due Diligence Requirements for Savings Associations in Determining Whether a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-15

    ... sound banking practices. Background Part 362 of the FDIC's regulations sets forth the requirements for... diligence to determine whether a security is eligible for investment under part 362. The federal banking...). This may include consideration of internal analyses, third-party research and analytics...

  7. Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

    PubMed

    Ståhle-Bäckdahl, M; Hägermark, O; Lins, L E; Törring, O; Hilliges, M; Johansson, O

    1989-06-01

    Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching. PMID:2746157

  8. Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression

    NASA Technical Reports Server (NTRS)

    Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

    2002-01-01

    A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.

  9. Negative regulation of parathyroid hormone-related protein expression by steroid hormones

    SciTech Connect

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Highlights: {yields} Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. {yields} Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. {yields} Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor {alpha}, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  10. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

    PubMed Central

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-01-01

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. PMID:26343649

  11. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone.

    PubMed

    Locklin, Rachel M; Khosla, Sundeep; Turner, Russell T; Riggs, B Lawrence

    2003-05-01

    Parathyroid hormone (PTH) has biphasic effects on bone: continuous treatment is catabolic whereas intermittent treatment is anabolic. The mechanism(s) responsible for these differing effects are still unclear, partly because of the previous non-availability of a model system in which effects on both formation and resorption indices could be studied concomitantly. In cultured marrow cells from 6-week old C57BL/6 mice, we demonstrated that 4 days of intermittent PTH treatment increased mRNA for osteoblast differentiation markers (Runx2, alkaline phosphatase (AP), and type I procollagen (COL1A1) whereas continuous treatment resulted in production of large numbers of TRAP-positive multinucleated osteoclasts. Although IGF-I mRNA did not increase after intermittent treatment, it was consistently higher than after continuous treatment, and the addition of an anti-IGF-I neutralizing antibody prevented the increase in bone formation indices observed with intermittent treatment. By contrast, after continuous treatment, gene expression of RANK ligand (RANKL) was increased and that of osteoprotegerin (OPG) was decreased, resulting in a 25-fold increase in the RANKL/OPG ratio. In this model system, the data suggest that intermittent PTH treatment enhances osteoblast differentiation through an IGF-I dependent mechanism and continuous PTH treatment enhances osteoclastogenesis through reciprocal increases in RANKL and decreases in OPG. PMID:12682918

  12. DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis.

    PubMed

    Wang, Yufeng; Lei, Rong; Zhuang, Xueqian; Zhang, Ning; Pan, Hong; Li, Gang; Hu, Jing; Pan, Xiaoqi; Tao, Qian; Fu, Da; Xiao, Jianru; Chin, Y Eugene; Kang, Yibin; Yang, Qifeng; Hu, Guohong

    2014-04-01

    Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-β signaling; however, little is known about how the TGF-β pathway is regulated during bone metastasis. Here we report that deleted in liver cancer 1 (DLC1) is an important regulator of TGF-β responses and osteolytic metastasis of breast cancer cells. In murine models, breast cancer cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis. Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested osteolysis and accelerated death in mice, while DLC1 overexpression suppressed bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated SMAD3 linker region phosphorylation and TGF-β-induced expression of parathyroid hormone-like hormone (PTHLH), leading to osteoclast maturation for osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK effectively reduced PTHLH production and breast cancer bone metastasis in vitro and in vivo. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. Overall, our findings define a stroma-dependent paradigm of Rho signaling in cancer and implicate Rho-TGF-β crosstalk in osteolytic bone metastasis. PMID:24590291

  13. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. )

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  14. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration.

    PubMed

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-01-01

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1-34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3-4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. PMID:26343649

  15. SP PROTEINS AND RUNX2 MEDIATE REGULATION OF MATRIX GLA PROTEIN (MGP) EXPRESSION BY PARATHYROID HORMONE

    PubMed Central

    Suttamanatwong, Supaporn; Jensen, Eric D; Shilling, Jody; Franceschi, Renny T.; Carlson, Ann E.; Mansky, Kim C.; Gopalakrishnan, Rajaram

    2009-01-01

    As part of its catabolic action in bone, parathyroid hormone (PTH) inhibits extracellular matrix mineralization. We previously showed that PTH dose-dependently induces matrix gla protein (MGP) expression in osteoblasts and this induction is at least partially responsible for PTH-mediated inhibition of mineralization. Recently, we identified PKA and ERK/MAPK as the key signaling pathways involved in PTH regulation of MGP expression. The goal of this study was to further characterize the mechanism by which PTH stimulates expression of MGP. Deletion analysis of the murine Mgp gene promoter identified a PTH-responsive region between -173 bp and -49 bp. Using gel-mobility shift assays we found that Sp1, Sp3 and Runx2 bind to distinct sites within this region. Mutation of either the Sp or the Runx2 site reduced MGP induction by PTH, while mutation of both sites completely abolished PTH responsiveness. Overexpression of Runx2 or Sp1 activated the Mgp reporter, while Sp3 was a dose-dependent repressor of MGP expression. Collectively, these data show that PTH regulates MGP gene transcription in osteoblasts through altered activities of Sp and Runx2 transcription factors. PMID:19306294

  16. Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone.

    PubMed

    de Groot, Theun; Kovalevskaya, Nadezda V; Verkaart, Sjoerd; Schilderink, Nathalie; Felici, Marco; van der Hagen, Eline A E; Bindels, René J M; Vuister, Geerten W; Hoenderop, Joost G

    2011-07-01

    The epithelial Ca(2+) channel transient receptor potential vanilloid 5 (TRPV5) constitutes the apical entry gate for active Ca(2+) reabsorption in the kidney. Ca(2+) influx through TRPV5 induces rapid channel inactivation, preventing excessive Ca(2+) influx. This inactivation is mediated by the last ∼30 residues of the carboxy (C) terminus of the channel. Since the Ca(2+)-sensing protein calmodulin has been implicated in Ca(2+)-dependent regulation of several TRP channels, the potential role of calmodulin in TRPV5 function was investigated. High-resolution nuclear magnetic resonance (NMR) spectroscopy revealed a Ca(2+)-dependent interaction between calmodulin and a C-terminal fragment of TRPV5 (residues 696 to 729) in which one calmodulin binds two TRPV5 C termini. The TRPV5 residues involved in calmodulin binding were mutated to study the functional consequence of releasing calmodulin from the C terminus. The point mutants TRPV5-W702A and TRPV5-R706E, lacking calmodulin binding, displayed a strongly diminished Ca(2+)-dependent inactivation compared to wild-type TRPV5, as demonstrated by patch clamp analysis. Finally, parathyroid hormone (PTH) induced protein kinase A (PKA)-dependent phosphorylation of residue T709, which diminished calmodulin binding to TRPV5 and thereby enhanced channel open probability. The TRPV5-W702A mutant exhibited a significantly increased channel open probability and was not further stimulated by PTH. Thus, calmodulin negatively modulates TRPV5 activity, which is reversed by PTH-mediated channel phosphorylation. PMID:21576356

  17. Molecular Mechanisms of Calmodulin Action on TRPV5 and Modulation by Parathyroid Hormone▿†

    PubMed Central

    de Groot, Theun; Kovalevskaya, Nadezda V.; Verkaart, Sjoerd; Schilderink, Nathalie; Felici, Marco; van der Hagen, Eline A. E.; Bindels, René J. M.; Vuister, Geerten W.; Hoenderop, Joost G.

    2011-01-01

    The epithelial Ca2+ channel transient receptor potential vanilloid 5 (TRPV5) constitutes the apical entry gate for active Ca2+ reabsorption in the kidney. Ca2+ influx through TRPV5 induces rapid channel inactivation, preventing excessive Ca2+ influx. This inactivation is mediated by the last ∼30 residues of the carboxy (C) terminus of the channel. Since the Ca2+-sensing protein calmodulin has been implicated in Ca2+-dependent regulation of several TRP channels, the potential role of calmodulin in TRPV5 function was investigated. High-resolution nuclear magnetic resonance (NMR) spectroscopy revealed a Ca2+-dependent interaction between calmodulin and a C-terminal fragment of TRPV5 (residues 696 to 729) in which one calmodulin binds two TRPV5 C termini. The TRPV5 residues involved in calmodulin binding were mutated to study the functional consequence of releasing calmodulin from the C terminus. The point mutants TRPV5-W702A and TRPV5-R706E, lacking calmodulin binding, displayed a strongly diminished Ca2+-dependent inactivation compared to wild-type TRPV5, as demonstrated by patch clamp analysis. Finally, parathyroid hormone (PTH) induced protein kinase A (PKA)-dependent phosphorylation of residue T709, which diminished calmodulin binding to TRPV5 and thereby enhanced channel open probability. The TRPV5-W702A mutant exhibited a significantly increased channel open probability and was not further stimulated by PTH. Thus, calmodulin negatively modulates TRPV5 activity, which is reversed by PTH-mediated channel phosphorylation. PMID:21576356

  18. Evaluation and management of radiation-induced thyroid and parathyroid abnormalities

    SciTech Connect

    Vassilopoulou-Sellin, R.

    1995-05-01

    The recently published analaysis of radiation-induced hyperparathyroidism by Schneider brings to the foreground an important albeit little discussed clinical problem: namely, the prospective evaluation strategy for optimizing treatment of such patients, especially in the preoperative setting. As the authors point out, childhood irradation for benign conditions is a recognized risk factor for the development of both hyperparathyroidism and thyroid cancer. In addition, therapeutic irradiation for childhood malignancies predisposes longterm cancer survivors to increased risk for thyroid cancer. It is likely that such high-dose irradiation also predisposes the patients toward the development of hyperparathroidism, although available supporting data remain limited and conflicting. It is not clear whether the cohort of patients who develop irradiation-induced hyperparathyroidism overlaps with the cohort at risk for thyroid nodules and thyroid cancer. Given the paucity of available documentation for parathyroid dysfunction relative to the plethora of literature for thyroid diseases, it would appear that hyperparathroidism may be a less frequent complication, although supporting data are not available for such a conclusion. 6 refs.

  19. Canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification

    SciTech Connect

    Karpf, D.B.; Arnaud, C.D.; King, K.; Bambino, T.; Winer, J.; Nyiredy, K.; Nissenson, R.A.

    1987-12-01

    Covalent labeling of the canine renal parathyroid hormone receptor with (/sup 125/I)bPTH(1-34) reveals several major binding components that display characteristic consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a ..beta..1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 (or 58,000 if the mass of bPTH(1-34) is excluded). The binding of (/sup 125/I)bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.

  20. The parathyroid hormone, its fragments and analogues--potent bone-builders for treating osteoporosis.

    PubMed

    Whitfield, J; Morley, P; Willick, G

    2000-06-01

    As populations age a rising number of men and women, but especially women during the first decade after menopause, become victims of a severe, accelerated loss of bone with crippling fractures known as osteoporosis. This often results in costly, prolonged hospitalisation and perhaps indirectly, death. Osteoporosis in women is caused by the menopausal oestrogen decline, which removes several key restraints on the generation, longevity and activity of bone-resorbing osteoclasts. Although there are many antiresorptive drugs on or coming onto the market (calcitonin, bisphosphonates, oestrogen and SERMS) that can slow or stop further bone loss, there are none that can restore lost bone mechanical strength by directly stimulating osteoblast activity and bone growth. However, there is a family of potent bone-building peptides, namely the 84 amino acid parathyroid hormone (PTH). Its 31 to 38 amino acid N-terminal fragments are currently in or about to enter clinical trials. We can predict that these peptides will be effective therapeutics for osteoporosis especially when supplemented with bisphosphonates or SERMs to protect the new bone from osteoclasts. These peptides should also accelerate the healing of fractures in persons of all ages and restore lost bone mass and mechanical strength to astronauts following their return to earth after long voyages in space. PMID:11060744

  1. Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration.

    PubMed

    Huber, Bruno C; Grabmaier, Ulrich; Brunner, Stefan

    2014-11-26

    Parathyroid hormone (PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders. PMID:25426261

  2. Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation

    PubMed Central

    Hussein, Omar; Walters, Bruce; Stroetz, Randolph; Valencia, Paul; McCall, Deborah

    2013-01-01

    Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and “collapse” of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with plasma membrane wounds in ex vivo mechanically ventilated rat lungs. Plasma membrane integrity was assessed by propidium iodide (PI) exclusion in confocal images of subpleural alveoli. Cyclic inflations of normal lungs from zero end-expiratory pressure to 40 cmH2O produced VT values of 56.9 ± 3.1 ml/kg and were associated with 0.12 ± 0.12 PI-positive cells/alveolus. A preceding tracheal instillation of normal saline (3 ml) reduced VT to 49.1 ± 6 ml/kg but was associated with a significantly greater number of wounded alveolar epithelial cells (0.52 ± 0.16 cells/alveolus; P < 0.01). Mechanical ventilation of completely saline-filled lungs with saline (VT = 52 ml/kg) to pressures between 10 and 15 cmH2O was associated with the least number of wounded epithelial cells (0.02 ± 0.02 cells/alveolus; P < 0.01). In mechanically ventilated, partially saline-filled lungs, the number of wounded cells increased substantially with VT, but, once VT was accounted for, wounding was independent of maximal PTP. We found that interfacial stress associated with the generation and destruction of liquid bridges in airspaces is the primary biophysical cell injury mechanism in mechanically ventilated lungs. PMID:23997173

  3. Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation.

    PubMed

    Hussein, Omar; Walters, Bruce; Stroetz, Randolph; Valencia, Paul; McCall, Deborah; Hubmayr, Rolf D

    2013-10-01

    Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and "collapse" of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with plasma membrane wounds in ex vivo mechanically ventilated rat lungs. Plasma membrane integrity was assessed by propidium iodide (PI) exclusion in confocal images of subpleural alveoli. Cyclic inflations of normal lungs from zero end-expiratory pressure to 40 cmH2O produced VT values of 56.9 ± 3.1 ml/kg and were associated with 0.12 ± 0.12 PI-positive cells/alveolus. A preceding tracheal instillation of normal saline (3 ml) reduced VT to 49.1 ± 6 ml/kg but was associated with a significantly greater number of wounded alveolar epithelial cells (0.52 ± 0.16 cells/alveolus; P < 0.01). Mechanical ventilation of completely saline-filled lungs with saline (VT = 52 ml/kg) to pressures between 10 and 15 cmH2O was associated with the least number of wounded epithelial cells (0.02 ± 0.02 cells/alveolus; P < 0.01). In mechanically ventilated, partially saline-filled lungs, the number of wounded cells increased substantially with VT, but, once VT was accounted for, wounding was independent of maximal PTP. We found that interfacial stress associated with the generation and destruction of liquid bridges in airspaces is the primary biophysical cell injury mechanism in mechanically ventilated lungs. PMID:23997173

  4. Social determinants of child abuse: evidence of factors associated with maternal abuse from the Egypt demographic and health survey

    PubMed Central

    Antai, Diddy; Braithwaite, Patrick; Clerk., George

    2016-01-01

    Abstract: Background: Child abuse or maltreatment is a significant global public health problem of unknown global prevalence. About 40 million children aged 0 - 14 years require health and social care globally. The prevalence, determinants, and trends of national or global rates of child abuse and maltreatment are largely unknown. Methods: Data for this retrospective cross-sectional study were derived from the 2005 Egyptian Demographic and Health Survey (2005 EDHS), and included 19474 women aged 15-49 years. Multivariate logistic regression analyses by stepwise regression, backward method were used to determine the independent contribution of the possible social determinants of child abuse, with the direction and magnitude of associations expressed as odds ratios (OR) and their 95% confident interval levels (95% CI). Results: Identified determinants of child abuse included exposure to intimate partner violence (IPV), justifying wife beating, exposure to generational IPV, and such factors as younger age of the women, male sex, partners’ lower education, poverty, residence in urban areas, younger children, and residence in households with 3 - 5 children. Conclusions: Experience of IPV, mothers’ justification of wife beating, and generational IPV were associated with elevated odds of child abuse. Findings indicate possible high levels of unmet child protection needs, and stress the need for professionals working with children to employ culturally-sensitive methods in investigating social determinants of child abuse. PMID:26401957

  5. Characterization of PHEX endopeptidase catalytic activity: identification of parathyroid-hormone-related peptide107-139 as a substrate and osteocalcin, PPi and phosphate as inhibitors.

    PubMed Central

    Boileau, G; Tenenhouse, H S; Desgroseillers, L; Crine, P

    2001-01-01

    Mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are responsible for X-linked hypophosphataemia, and studies in the Hyp mouse model of the human disease implicate the gene product in the regulation of renal phosphate (P(i)) reabsorption and bone mineralization. Although the mechanism for PHEX action is unknown, structural homologies with members of the M13 family of endopeptidases suggest a function for PHEX protein in the activation or degradation of peptide factors involved in the control of renal P(i) transport and matrix mineralization. To determine whether PHEX has endopeptidase activity, we generated a recombinant soluble, secreted form of human PHEX (secPHEX) and tested the activity of the purified protein with several peptide substrates, including a variety of bone-related peptides. We found that parathyroid-hormone-related peptide(107-139) is a substrate for secPHEX and that the enzyme cleaves at three positions within the peptide, all located at the N-terminus of aspartate residues. Furthermore, we show that osteocalcin, PP(i) and P(i), all of which are abundant in bone, are inhibitors of secPHEX activity. Inhibition of secPHEX activity by osteocalcin was abolished in the presence of Ca(2+). We suggest that PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and Ca(2+) and, in the latter case, the regulation requires the participation of osteocalcin. PMID:11311133

  6. Parathyroid hormone PTH(1–34) increases the volume, mineral content, and mechanical properties of regenerated mineralizing tissue after distraction osteogenesis in rabbits

    PubMed Central

    2009-01-01

    Background and purpose Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans. Methods 72 New Zealand White rabbits underwent tibial mid-diaphyseal osteotomy and the callus was distracted 1 mm/day for 10 days. The rabbits were divided into 3 groups, which received injections of PTH 25 µg/kg/day for 30 days, saline for 10 days and PTH 25 µg/kg/day for 20 days, or saline for 30 days. At the end of the study, the rabbits were killed and the bone density was evaluated with DEXA. The mechanical bone strength was determined by use of a 3-point bending test. Results In the 2 PTH-treated groups the regenerate callus ultimate load was 33% and 30% higher, absorbed energy was 100% and 65% higher, BMC was 61% and 60% higher, and callus tissue volume was 179% and 197% higher than for the control group. Interpretation We found that treatment with PTH during distraction osteogenesis resulted in substantially higher mineralized tissue volume, mineral content, and bending strength. This suggests that treatment with PTH may benefit new bone formation during distraction osteogenesis and could form a basis for clinical application of this therapy in humans. PMID:19995322

  7. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    PubMed Central

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the

  8. Diabetes, HIV and other health determinants associated with absenteeism among formal sector workers in Namibia

    PubMed Central

    2012-01-01

    Background As countries in sub-Saharan Africa develop their economies, it is important to understand the health of employees and its impact on productivity and absenteeism. While previous studies have assessed the impact of single conditions on absenteeism, the current study evaluates multiple health factors associated with absenteeism in a large worker population across several sectors in Namibia. Methods From March 2009 to June 2010, PharmAccess Namibia conducted a series of cross-sectional surveys of 7,666 employees in 7 sectors of industry in Namibia. These included a self-reported health questionnaire and biomedical screenings for certain infectious diseases and non-communicable disease (NCD) risk factors. Data were collected on demographics, absenteeism over a 90-day period, smoking behavior, alcohol use, hemoglobin, blood pressure, blood glucose, cholesterol, waist circumference, body mass index (BMI), HIV status, and presence of hepatitis B antigens and syphilis antibodies. The associations of these factors to absenteeism were ascertained using negative binomial regression. Results Controlling for demographic and job-related factors, high blood glucose and diabetes had the largest effect on absenteeism (IRR: 3.67, 95%CI: 2.06-6.55). This was followed by anemia (IRR: 1.59, 95%CI: 1.17-2.18) and being HIV positive (IRR: 1.47; 95%CI: 1.12-1.95). In addition, working in the fishing or services sectors was associated with an increased incidence of sick days (IRR: 1.53, 95%CI: 1.23-1.90; and IRR: 1.70, 95%CI: 1.32-2.20 respectively). The highest prevalence of diabetes was in the services sector (3.6%, 95%CI:-2.5-4.7). The highest prevalence of HIV was found in the fishing sector (14.3%, 95%CI: 10.1-18.5). Conclusion Both NCD risk factors and infectious diseases are associated with increased rates of short-term absenteeism of formal sector employees in Namibia. Programs to manage these conditions could help employers avoid costs associated with absenteeism. These

  9. Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

    PubMed Central

    Nelson, Patricia A.; Khodadoust, Mojgan; Prodhomme, Thomas; Spencer, Collin; Patarroyo, Juan Carlos; Varrin-Doyer, Michel; Ho, Joseph D.; Stroud, Robert M.; Zamvil, Scott S.

    2010-01-01

    Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models. PMID:21151500

  10. Determinants of potential drug–drug interaction associated dispensing in community pharmacies in the Netherlands

    PubMed Central

    Becker, Matthijs L.; Caspers, Peter W. J.; Kallewaard, Marjon; Bruinink, Riekert J.; Kylstra, Nico B.; Heisterkamp, Siem; de Valk, Vincent; van der Veen, André A.

    2006-01-01

    Objective: There are many drug–drug interactions (D–DI) of which some may cause severe adverse patient outcomes. Dispensing interacting drug combinations should be avoided when the risks are higher than the benefits. The objective of this study was to identify determinants of dispensing undesirable interacting drug combinations by community pharmacies in the Netherlands. Methods: A total of 256 Dutch community pharmacies were selected, based on the dispensing of 11 undesirable interacting drug combinations between January 1st, 2001 and October 31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for Health Care (IHC) concerning their process and structure characteristics. Main outcome measure: The number of times the 11 undesirable interacting drug combinations were dispensed. Results: Two hundred and forty-six questionnaires (response rate 96.1%) were completed. Dispensing determinants were only found for the D–DI between macrolide antibiotics and digoxin but not for the other 10 D–DIs. Pharmacies using different medication surveillance systems differed in the dispensing of this interacting drug combination, and pharmacies, which were part of a health care centre dispensed this interacting drug combination more often. Conclusion: Medication surveillance in Dutch community pharmacies seems to be effective. Although for most D–DIs no determinants were found, process and structure characteristics may have consequences for the dispensing of undesirable interacting drug combinations. PMID:17187223

  11. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

    PubMed

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  12. Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

    PubMed Central

    Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

    2016-01-01

    Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

  13. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus

    PubMed Central

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness. PMID:26504422

  14. Determination of factors associated with natural soil suppressivity to potato common scab.

    PubMed

    Sagova-Mareckova, Marketa; Daniel, Ondrej; Omelka, Marek; Kristufek, Vaclav; Divis, Jiri; Kopecky, Jan

    2015-01-01

    Common scab of potatoes is a disease, which is difficult to manage due to complex interactions of the pathogenic bacteria (Streptomyces spp.) with soil, microbial community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic two sites (Vyklantice and Zdirec) were selected for a study of common scab disease suppressivity. At both sites, a field with low disease severity occurs next to one with high severity and the situation was regularly observed over four decades although all four fields undergo a crop rotation. In the four fields, quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic gene cluster of thaxtomin, the main pathogenicity factor of common scab, were analyzed by real-time PCR. Microbial community structure was compared by terminal fragment length polymorphism analysis. Soil and potato periderm were characterized by contents of carbon, nitrogen, phosphorus, sulphur, calcium, magnesium, and iron. Quality of organic matter was assessed by high performance liquid chromatography of soil extracts. The study demonstrated that the suppressive character of the fields is locally specific. At Zdirec, the suppressivity was associated with low txtB gene copies in bulk soil, while at Vyklantice site it was associated with low txtB gene copies in the tuberosphere. The differences were discussed with respect to the effect of abiotic conditions at Zdirec and interaction between potato plant and soil microbial community at Vyklantice. Soil pH, Ca soil content or cation concentrations, although different were not in the range to predict the disease severity. Low severity of common scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that oligotrophic conditions may be favorable to common scab suppression. PMID:25612311

  15. Determination of Factors Associated with Natural Soil Suppressivity to Potato Common Scab

    PubMed Central

    Sagova-Mareckova, Marketa; Daniel, Ondrej; Omelka, Marek; Kristufek, Vaclav; Divis, Jiri; Kopecky, Jan

    2015-01-01

    Common scab of potatoes is a disease, which is difficult to manage due to complex interactions of the pathogenic bacteria (Streptomyces spp.) with soil, microbial community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic two sites (Vyklantice and Zdirec) were selected for a study of common scab disease suppressivity. At both sites, a field with low disease severity occurs next to one with high severity and the situation was regularly observed over four decades although all four fields undergo a crop rotation. In the four fields, quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic gene cluster of thaxtomin, the main pathogenicity factor of common scab, were analyzed by real-time PCR. Microbial community structure was compared by terminal fragment length polymorphism analysis. Soil and potato periderm were characterized by contents of carbon, nitrogen, phosporus, sulphur, calcium, magnesium, and iron. Quality of organic matter was assessed by high performance liquid chromatography of soil extracts. The study demonstrated that the suppressive character of the fields is locally specific. At Zdirec, the suppressivity was associated with low txtB gene copies in bulk soil, while at Vyklantice site it was associated with low txtB gene copies in the tuberosphere. The differences were discussed with respect to the effect of abiotic conditions at Zdirec and interaction between potato plant and soil microbial community at Vyklantice. Soil pH, Ca soil content or cation concentrations, although different were not in the range to predict the disease severity. Low severity of common scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that oligotrophic conditions may be favorable to common scab suppression. PMID:25612311

  16. Determination of Rare Earth Elements in Human Sperm and Association with Semen Quality.

    PubMed

    Marzec-Wróblewska, Urszula; Kamiński, Piotr; Łakota, Paweł; Ludwikowski, Grzegorz; Szymański, Marek; Wasilow, Karolina; Stuczyński, Tomasz; Buciński, Adam; Jerzak, Leszek

    2015-08-01

    The aim of the present study was to measure lanthanum (La), cerium (Ce), europium (Eu), and gadolinium (Gd) concentrations in human semen and correlate the results with sperm quality. The median semen content of La was 19.5 µg kg(-1) dry weight (dw) (range 2.27-269), of Ce was 41.9 µg kg(-1) dw (range 4.52 to 167), of Eu was 0.68 µg kg(-1) dw (range 0.06-1.95), of Gd was 3.19 µg kg(-1) dw (range 0.38-12.0), and of calcium (Ca) was 4063 mg kg(-1) dw (range 484-17,191). Concentrations of La, Ce, Eu, Gd, and Ca were significantly lower in nondrinkers' semen than in semen from drinkers. Significant differences were detected between La, Ce, Eu, Gd, and Ca concentrations in semen from nondrinkers and moderate drinkers. Concentrations of La, Ce, and Gd in semen of short-term smokers were significantly lower than those in extremely long-term smokers. Significant differences were also detected between La concentration in semen from a group of short-term smokers and that of a group of long-term smokers. Positive correlations were found between La, Ce, Eu, Gd, and Ca concentrations in semen. La, Ce, Gd, and Ca concentrations in semen were positively associated with progressive motility and percentage of normal spermatozoa. Positive correlations were found between Ca and sperm concentration. Concentrations of La, Ce, and Gd were negatively associated with sperm concentration, whilst Ca concentration was negatively associated with volume of ejaculate. At the examined level, La, Ce, Eu, and Gd did not affect sperm quality, whereas alcohol consumption and smoking might have increased the level of rare earth elements in semen. PMID:25762379

  17. Methodological Challenges in Determining Longitudinal Associations Between Anticholinergic Drug Use and Incident Cognitive Decline

    PubMed Central

    Kashyap, Mandavi; Belleville, Sylvie; Mulsant, Benoit H; Hilmer, Sarah N; Paquette, Amelie; Tu, Le Mai; Tannenbaum, Cara

    2014-01-01

    Objectives To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies. Design Longitudinal cohort study. Setting Outpatient clinics, Quebec, Canada. Participants Individuals aged 60 and older without dementia or depression (n = 102). Measurements Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression. Results The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1–25.8), ADS (OR = 5.7, 95% CI = 1.1–27.7), and ARS (OR = 6.5, 95% CI = 1.34–32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8–15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1–8.0). No associations were observed using the DSM-V criteria or RCI method. Conclusion The choice of different methods for defining drug exposure and cognitive decline

  18. The Transtheoretical model for fruit, vegetable and fish consumption: associations between intakes, stages of change and stage transition determinants

    PubMed Central

    De Vet, Emely; de Nooijer, Jascha; de Vries, Nanne K; Brug, Johannes

    2006-01-01

    Background Cardiovascular diseases are caused by multiple behavioral factors, including different dietary factors. We examined to what extent fruit, vegetable and fish consumption are related, and whether behavioral determinants vary across these dietary behaviors from a Transtheoretical model perspective. Methods Data were collected among 1142 participants (T0; response rate 46%) selected from an Internet panel, who were followed-up one-week later (T1; N = 1055, response rate 92%). Mean age was 35.4 (SD = 11.9) years, 35% was male, and most respondents were of Dutch origin (90%). Of the respondents, 13%, 44% and 43% had a low, medium or high level of education, respectively. Electronic questionnaires assessed fruit, vegetable and fish intake (food frequency questionnaires), stages of change, decisional balance and self-efficacy, for each of these three behaviors. Results Stages of change and (changes in) fruit, vegetable and fish intake were only weakly associated; decisional balance and self-efficacy were more strongly associated. Some presumed predictors of stage transitions were similar for fruit, vegetable, and fish intake, i.e., strong pros predicted progress out of precontemplators and low self-efficacy predicted relapse from action/maintenance for all behaviors. However, progress out of contemplation and out of preparation showed different patterns for fruit, vegetable and fish intake. Conclusion The weak associations between intakes and potential determinants for fruit, vegetable, and fish consumption do not warrant an integrated dietary change approach targeting the same determinants for each behavior. PMID:16784520

  19. Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control

    NASA Astrophysics Data System (ADS)

    Kagami, Haruna; Akutsu, Tatsuya; Maegawa, Shingo; Hosokawa, Hiroshi; Nacher, Jose C.

    2015-10-01

    Deciphering the association between life molecul