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Theresa A Guise - One of the best experts on this subject based on the ideXlab platform.
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tumor necrosis factor enhances parathyroid hormone related protein induced Hypercalcemia and bone resorption without inhibiting bone formation in vivo
Cancer Research, 1997Co-Authors: Harry L Uy, Theresa A Guise, Gregory R Mundy, Colin R Dunstan, Brendan F Boyce, Beryl Story, David G RoodmanAbstract:Abstract Humoral Hypercalcemia of malignancy results from the effects of tumor-produced factors on bone, kidney, and intestine that disrupt normal calcium homeostasis. Although parathyroid hormone-related protein (PTHrP) is a major mediator of the syndrome, tumors also produce other hypercalcemic factors, such as tumor necrosis factor (TNF), which may modulate the effects of PTHrP. It has been postulated that TNF may counteract the stimulatory effects of PTHrP on bone formation. To examine the effects of TNF on PTHrP-induced changes in calcium and bone metabolism, a murine tumor model of Hypercalcemia was used. Nude mice were inoculated with Chinese hamster ovarian (CHO) cells expressing human TNF (CHO/TNF) or nontransfected CHO cells (CHO/-) and further treated with injections of human PTHrP(1–34) or vehicle. The effects of TNF, PTHrP, and the combination of the two factors on blood ionized calcium, osteoclast recruitment, and bone histomorphometry were evaluated. Mice bearing CHO/TNF tumors that were injected with PTHrP had significantly higher calcium concentrations, increased committed osteoclast progenitors, and mature osteoclasts as well as enhanced bone resorption compared with mice bearing CHO/TNF tumors injected with vehicle or those bearing CHO/- tumors injected with PTHrP or vehicle. A 2-fold increase in new woven bone formed in the calvaria at sites of previous bone resorption was observed in CHO/TNF mice treated with PTHrP. Bone formation rates in the vertebrae were similar in both CHO/- and CHO/TNF mice treated with PTHrP. These data demonstrate that the hypercalcemic effects of PTHrP are enhanced by TNF and that this effect is due to the increased production of committed osteoclast precursors with a subsequent increase in osteoclastic bone resorption. Furthermore, PTHrP caused a coupled increase in osteoclastic bone resorption and new bone formation that was not inhibited by TNF. These findings highlight the complex interactions that may occur between tumor-produced factors on bone that result in malignancy-associated Hypercalcemia and suggest that TNF may not be responsible for the decreased bone formation seen in some patients with this condition.
Yaoxia Liu - One of the best experts on this subject based on the ideXlab platform.
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spontaneous remission after a hypercalcemic crisis caused by an intracystic hemorrhage of bilateral parathyroid adenomas a case report and literature review
Frontiers in Endocrinology, 2021Co-Authors: Yaoxia Liu, Hui Liu, Han Yang, Jingtao Qiao, Tao Wei, Tao WangAbstract:Background: Hyperparathyroidism is a common cause of Hypercalcemia; however, spontaneous remission after a hypercalcemic crisis caused by an intracystic hemorrhage of parathyroid adenomas is very rare. The question, then, is “What is the best choice in such cases--conservative treatment or surgery?” Method: A 47-year-old male patient with primary hyperparathyroidism and a hypercalcemic crisis is reported. Hypercalcemia was spontaneously relieved thereafter. The post-operative pathology results indicated an intracystic hemorrhage of bilateral parathyroid adenomas. Results: After the case report, a literature review is also included to summarize the clinical features of this patient and to provide special reference for clinical diagnosis and treatment of similar cases. Conclusions: The choice of surgical timing for such cases can be made based on the comprehensive consideration of clinical symptoms and changes in parathyroid function.
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Spontaneous Remission After a Hypercalcemic Crisis Caused by an Intracystic Hemorrhage of Bilateral Parathyroid Adenomas: A Case Report and Literature Review
'Frontiers Media SA', 2021Co-Authors: Yaoxia Liu, Hui Liu, Han Yang, Jingtao Qiao, Tao Wei, Tao WangAbstract:BackgroundHyperparathyroidism is a common cause of Hypercalcemia; however, spontaneous remission after a hypercalcemic crisis caused by an intracystic hemorrhage of parathyroid adenomas is very rare. The question, then, is “What is the best treatment strategy for this type of case?”MethodA 47-year-old male patient with primary hyperparathyroidism and a hypercalcemic crisis is reported. Hypercalcemia was spontaneously relieved thereafter. Postoperative paraffin pathology results indicated an intracystic hemorrhage of bilateral parathyroid adenomas.ResultsAfter the case report, a literature review is also included to summarize the clinical features of this patient and to provide special reference for clinical diagnosis and treatment of similar cases.ConclusionsThe choice of surgical timing for such cases can be made based on the comprehensive consideration of clinical symptoms and changes in parathyroid function
Nicholas Frank - One of the best experts on this subject based on the ideXlab platform.
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Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999–2016)
Equine veterinary journal, 2019Co-Authors: E. B. Gorenberg, Amy L. Johnson, K. G. Magdesian, Francois-rene Bertin, L. R. R. Costa, M.j.p. Theelen, S. A. Durward-akhurst, C. Cruz Villagrán, H.b. Carslake, Nicholas FrankAbstract:Background: Primary hyperparathyroidism is uncommon in equids. Objectives: To describe the diagnostic findings and efficacy of treatment in equids with primary hyperparathyroidism. Study design: Retrospective case series describing 16 horses and one mule. Methods: Cases were identified by retrospective review of records at Cornell University and via an ACVIM listserv query. Inclusion criteria were an equid with Hypercalcemia, normal renal function and high parathyroid hormone (PTH) or histopathological diagnosis of a parathyroid adenoma. Equids with normal PTH and PTH-related protein (PTHrP) in the face of Hypercalcemia were included as suspect cases. Results: The most common presenting complaints were weight loss (12/17) and Hypercalcemia (10/17). PTH was above reference range in 12/17 cases. Suspected parathyroid tumours were localised in 12/14 equids imaged using ultrasonography alone (2/3), technetium 99m Tc sestamibi scintigraphy alone (1/1) or both modalities (9/10). Three horses did not have imaging performed. Surgical exploration successfully excised tumours in six of 10 cases. Five were located at the thoracic inlet, and surgery resulted in complete cure. One tumour was excised from the thyroid lobe, and the horse remained hypercalcemic. Four other cases explored surgically, four treated medically and three that were not treated also remained hypercalcemic. Main limitations: The small study size prohibited statistical analysis. Conclusions: Parathyroid adenomas in equids can be successfully localised with ultrasonography and scintigraphy. Surgical excision appears more likely to be successful for single gland disease at the thoracic inlet.
Kanji Sato - One of the best experts on this subject based on the ideXlab platform.
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urinary excretion of parathyroid hormone related protein fragments in patients with humoral Hypercalcemia of malignancy and hypercalcemic tumor bearing nude mice
Journal of Bone and Mineral Research, 2009Co-Authors: Hidehito Imamura, Kanji Sato, Kazuo Shizume, Tomoko Satoh, Keizo Kasono, Minoru Ozawa, Eiji Ohmura, Toshio Tsushima, Hiroshi DemuraAbstract:To investigate whether parathyroid hormone-related protein (PTHrP), a Hypercalcemia-inducing factor responsible for malignancy-associated Hypercalcemia (MAH), is excreted into urine of these patients, radioimmunoassay was established using antiserum specific for the C-terminal region of PTHrP-(127–141). Immunoreactive PTHrP (iPTHrP) was detected in the urine of all patients with MAH (n = 6) in whom nephrogenous cyclic AMP excretion was elevated. However, iPTHrP was not detected in the urine of normal subjects (n = 25) or hypercalcemic patients with primary hyperparathyroidism (n = 8). In normocalcemic patients with malignant disorders iPTHrP was not detected in the urine in most cases (24 of 25 patients) but was detectable in 1 of 25 patients. iPTHrP was also detected in the urine of hypercalcemic nude mice transplanted with PTHrP-producing tumors, but not in the urine of control and normocalcemic nude mice transplanted with PTHrP-nonproducing tumor. Furthermore, size-exclusion high-performance liquid chromatography revealed that the molecular weight of iPTHrP is about 2000–6000 daltons in the urine of patients as well as tumor-bearing nude mice. These data indicate that the fragments of the C-terminal region of PTHrP are excreted into the urine of patients with MAH and in a few normocalcemic patients with malignancies, suggesting that the measurement of iPTHrP in the urine is potentially useful in the differential diagnosis of Hypercalcemia, particularly in differentiating humoral Hypercalcemia of malignancy and primary hyperparathyroidism.
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Hypercalcemia during pregnancy puerperium and lactation review and a case report of hypercalcemic crisis after delivery due to excessive production of pth related protein pthrp without malignancy humoral Hypercalcemia of pregnancy
Endocrine Journal, 2008Co-Authors: Kanji SatoAbstract:Hypercalcemia during pregnancy or after delivery is uncommon, and mostly associated with primary hyperparathyroidism (PHPT). If unrecognized, it may increase maternal and fetal morbidity. In a very few patients with PHPT, hypercalcemic crisis develops during pregnancy and particularly after delivery, since calcium transport from the mother to the fetus is abruptly disrupted. Hypercalcemia may also develop in pregnant women due to PTH-related protein (PTHrP)-producing malignant tumors (humoral Hypercalcemia of malignancy). Since PTHrP is produced physiologically in fetal and maternal tissues, Hypercalcemia may occasionally develop during pregnancy, puerperium, and lactation due to excessive production of PTHrP in the placenta and/or mammary glands. PTHrP may also be involved in milk-alkali syndrome that develops during pregnancy. Although non-malignant Hypercalcemia is usually mild, we report a 28-years-old pregnant woman who developed hypercalcemic crisis after normal delivery of an infant. On the first postpartum day, the corrected serum calcium concentration increased to 19.4 mg/dl with a markedly increased serum level of PTHrP (28.4 pmol/L) (normal <1.1 pmol/L). After administration of saline and pamidronate, the serum levels of calcium and PTHrP rapidly normalized. Extensive examination revealed no malignant lesion, suggesting that the placenta may have been producing an excessive amount of PTHrP (humoral Hypercalcemia of pregnancy). We review case reports of non-malignant hypercalcemic crisis associated with pregnancy indexed in PubMed in which serum levels of intact PTH and/or PTHrP were described, and stress that rapid control of Hypercalcemia is mandatory to save the life of the mother and the infant.
Hiroshi Demura - One of the best experts on this subject based on the ideXlab platform.
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passive immunization with anti parathyroid hormone related protein monoclonal antibody markedly prolongs survival time of hypercalcemic nude mice bearing transplanted human pthrp producing tumors
Journal of Bone and Mineral Research, 2009Co-Authors: M Kanji D Sato, Naokazu Nagata, Y Yamakawa, Kazuo Shizume, Tomoko Satoh, Kyoko Nohtomi, Hiroshi Demura, Takuhiko Akatsu, Tadashi Kasahara, Hiroyuki OhkawaAbstract:: Malignancy-associated Hypercalcemia is mainly caused by excessive production of parathyroid hormone-related protein (PTHrP) by the tumor. Using anti-PTHrP-(1-34) monoclonal murine antibody (anti-PTHrP MoAb), we studied whether repeated injection of the homologous antibody would continuously decrease the serum calcium concentration in hypercalcemic nude mice bearing transplanted human PTHrP-producing tumors, leading to prolongation of their survival time. Daily SC injections of anti-PTHrP MoAb decreased the serum calcium concentration almost to within the normal range in nude mice bearing transplanted human PTHrP-producing tumors (T3M-1, EC-GI, PC-3, and FA-6) but not in a nude mouse bearing a transplanted parathyroid carcinoma. The antibody did not affect FA-6 tumor growth either in vitro or in vivo. Pancreatic carcinoma cells (FA-6), which caused the most severe Hypercalcemia, were inoculated into 6-week-old nude mice. When severe Hypercalcemia (approximately 19 mg/dl) had developed, daily SC injection of anti-PTHrP MoAb was started. Within 18 days of this time point, all untreated tumor-bearing mice (n = 10) died of Hypercalcemia and cachexia, whereas all the treated mice (n = 10) showed an increase in body weight and survived for at least 25 days. Histologic examination of the treated mice revealed a marked decrease in osteoclastic bone resorption, without toxicologic findings in the kidney and liver. These results suggest that passive immunization against PTHrP can continuously ameliorate the Hypercalcemia and markedly prolong the survival time of severely hypercalcemic, tumor-bearing mice. If a human monoclonal antibody against PTHrP-(1-34) could be developed, then passive immunization would be potentially one of the most effective therapies for patients with malignancy-associated Hypercalcemia due to excessive production of PTHrP.
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urinary excretion of parathyroid hormone related protein fragments in patients with humoral Hypercalcemia of malignancy and hypercalcemic tumor bearing nude mice
Journal of Bone and Mineral Research, 2009Co-Authors: Hidehito Imamura, Kanji Sato, Kazuo Shizume, Tomoko Satoh, Keizo Kasono, Minoru Ozawa, Eiji Ohmura, Toshio Tsushima, Hiroshi DemuraAbstract:To investigate whether parathyroid hormone-related protein (PTHrP), a Hypercalcemia-inducing factor responsible for malignancy-associated Hypercalcemia (MAH), is excreted into urine of these patients, radioimmunoassay was established using antiserum specific for the C-terminal region of PTHrP-(127–141). Immunoreactive PTHrP (iPTHrP) was detected in the urine of all patients with MAH (n = 6) in whom nephrogenous cyclic AMP excretion was elevated. However, iPTHrP was not detected in the urine of normal subjects (n = 25) or hypercalcemic patients with primary hyperparathyroidism (n = 8). In normocalcemic patients with malignant disorders iPTHrP was not detected in the urine in most cases (24 of 25 patients) but was detectable in 1 of 25 patients. iPTHrP was also detected in the urine of hypercalcemic nude mice transplanted with PTHrP-producing tumors, but not in the urine of control and normocalcemic nude mice transplanted with PTHrP-nonproducing tumor. Furthermore, size-exclusion high-performance liquid chromatography revealed that the molecular weight of iPTHrP is about 2000–6000 daltons in the urine of patients as well as tumor-bearing nude mice. These data indicate that the fragments of the C-terminal region of PTHrP are excreted into the urine of patients with MAH and in a few normocalcemic patients with malignancies, suggesting that the measurement of iPTHrP in the urine is potentially useful in the differential diagnosis of Hypercalcemia, particularly in differentiating humoral Hypercalcemia of malignancy and primary hyperparathyroidism.