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Sample records for hypercalcemia

  1. Hypercalcemia

    MedlinePlus

    ... or health problems such as, Paget's disease and sarcoidosis. An inherited condition that affects the body's ability ... hypercalcemia due to conditions such as cancer or sarcoidosis may not do well. This is most often ...

  2. Hypercalcemia

    MedlinePlus

    ... nephrocalcinosis ) Dehydration High blood pressure Kidney failure Kidney stones Psychological: Depression Difficulty concentrating or thinking Skeletal: Bone cysts Fractures Osteoporosis These complications of long-term hypercalcemia are uncommon today.

  3. Problems in medicine: hypercalcemia

    SciTech Connect

    Weller, R.E.

    1985-06-01

    The pathophysiologic mechanisms for hypercalcemia are reviewed and a diagnostic approach to determining the cause of hypercalcemia in clinical cases in dogs and cats is recommended. 5 refs., 1 fig., 1 tab. (ACR)

  4. Immobilization induced hypercalcemia

    PubMed Central

    Cano-Torres, Edgar Alonso; González-Cantú, Arnulfo; Hinojosa-Garza, Gabriela; Castilleja-Leal, Fernando

    2016-01-01

    Summary Immobilization hypercalcemia is an uncommon diagnosis associated with increased bone remodeling disorders and conditions associated with limited movement such as medullar lesions or vascular events. Diagnosis requires an extensive evaluation to rule out other causes of hypercalcemia. This is a report of a woman with prolonged immobilization who presented with severe hypercalcemia. This case contributes to identification of severe hypercalcemia as a result of immobility and the description of bone metabolism during this state. PMID:27252745

  5. Hypercalcemia. Pathophysiological aspects.

    PubMed

    Žofková, I

    2016-01-01

    The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in these regulations may lead to hyper- or hypocalcemia. Hypercalcemia is a potentionally life-threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalcemia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long-term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalcemia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search. PMID:26596315

  6. High Blood Calcium (Hypercalcemia)

    MedlinePlus

    ... as sarcoidosis • Hormone disorders, such as overactive thyroid (hyperthyroidism) • A genetic condition called familial hypocalciuric hypercalcemia • Kidney ... topics: www.hormone.org (search for PHPT, calcium, hyperthyroidism, or osteoporosis) • MedlinePlus (National Institutes of Health-NIH): ...

  7. Imaging studies in hypercalcemia.

    PubMed

    Cecchin, D; Motta, R; Zucchetta, P; Bui, F; Basso, S M M; Lumachi, F

    2011-01-01

    Hypercalcemia is a relatively common clinical problem, mainly (>90%) related to primary hyperparathyroidism (HPT) and malignancies. The anatomical and functional imaging techniques available for locating enlarged parathyroid glands include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging techniques. The most commonly employed are US and parathyroid scintigraphy, while CT, MRI, positron emission tomography (PET)/CT, and selective venous sampling are generally used in patients with persistent or recurrent HPT, or when findings of non-invasive studies are negative or conflicting. The reported accuracy is 57-93%, 54-93%, and up to 95% for US, (99m)Tc-sestamibi scintigraphy, and the two modalities combined, respectively. A multimodality approach (x-ray, whole-body scintigraphy, CT, MRI, and PET) is usually recommended for whole body assessment in cases of cancer-induced hypercalcemia (CIH). Imaging studies should evaluate each organ (i.e. breast, kidney, prostate, parathyroid) potentially involved in the pathogenesis of hypercalcemia in patients with CIH. In cases of skeletal metastases, when findings on plain x-ray or bone scans are uncertain, any unexplained region of abnormal uptake should be examined by MRI and/or ¹⁸F-fluoro-2- deoxyglucose (FDG)-PET/CT, which has proved more accurate than classical bone scintigraphy, especially for dealing with hematologic malignancies. A number of radionuclide tracers, other than ¹⁸F-FDG, are available for use in selected cases to locate specific tumors (i.e. ⁶⁸Ga for neuroendocrine tumors). This is a review of recently published information on the imaging techniques currently available for patients with hypercalcemia. PMID:21756234

  8. Severe hypercalcemia due to teriparatide

    PubMed Central

    Karatoprak, Cumali; Kayatas, Kadir; Kilicaslan, Hanifi; Yolbas, Servet; Yazimci, Nurhan Aliye; Gümüskemer, Tolga; Demirtunç, Refik

    2012-01-01

    Osteoporosis that is by far the most common metabolic bone disease, has been defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Anabolic therapy with teriparatide, recombinant human parathyroid hormone (PTH 1-34), stimulates bone formation and resorption and improves trabecular and cortical microarchitecture. Teriparatide is indicated for the treatment of men and postmenopausal women with osteoporosis who are at high risk for fracture, including those who have failed or are intolerant of previous osteoporosis therapy. In conclusion, although teriparatide seems quite effective in the treatment of osteoporosis, it may cause life-threatening hypercalcemia. Therefore, patients should be closely monitored if symptoms of hypercalcemia are present during teriparatide treatment. Sustained hypercalcemia due to teriparatide treatment can not be seen in literature so we wanted to emphasize that severe hypercalcemia may develop due to teriperatide. PMID:22529492

  9. Artifactual hypercalcemia in multiple myeloma

    SciTech Connect

    Annesley, T.M.; Burritt, M.F.; Kyle, R.A.

    1982-09-01

    A calcium-binding IgG K monoclonal protein in a patient with multiple myeloma and asymptomatic hypercalcemia was recognized, isolated, and characterized. In addition to binding by the whole IgG molecules, calcium was bound by purified Fab fragments and recombined heavy and light chains. In a competitive binding study, the isolated myeloma protein did not bind magnesium. Recognition of calcium-binding myeloma proteins is important in order to avoid therapy for hypercalcemia.

  10. [Hypercalcemia revealing sarcoidosis in a child].

    PubMed

    Kinné, M; Filleron, A; Salet, R; Saumet, L; Baron Joly, S; Tran, T A

    2016-05-01

    Sarcoidosis is a systemic granulomatosis disease with a classic triad of presentation: typical clinical and radiological signs, presence of tuberculoid granuloma without caseum in histopathology, and exclusion of other causes of granulomatosis, especially tuberculosis. Sarcoidosis is rare in the general population, and even more so in children. In the literature, few cases of sarcoidosis associated with hypercalcemia have been reported in children. We report here the case of a 14-year-old boy with bone marrow and lymph node sarcoidosis suspected, based on poor general condition with hypercalcemia. The patient was treated with hydration, diuretics, and bisphosphonates with good results. We also performed a literature review of published cases of hypercalcemia since 1990 with a diagnosis of sarcoidosis in children, comparing 23 cases (including ours) on clinical and epidemiological, biological, imaging, and histopathological diagnosis. When hypercalcemia is present in the initial clinical presentation, the diagnosis of sarcoidosis is usually made in younger children. Classical locations of the lesions, including lung, skin, and lymph nodes, were highly suggestive of sarcoidosis. Corticosteroids are commonly used to treat sarcoidosis lesions including hypercalcemia. In conclusion, sarcoidosis in children remains difficult to diagnose because the disease is rare and it is common to have nonspecific symptoms in the clinical picture (with diagnosis delayed between 3 months and several years). The classic triad is not always present. Sarcoidosis should be systematically considered and investigated in case of hypercalcemia of unknown cause in children. PMID:27021884

  11. Studies on the pathogenesis of cancer hypercalcemia.

    PubMed Central

    Laird Myers, W. P.; Bockman, R.

    1977-01-01

    The pathogenesis of hypercalcemia in cancer continues to challenge the clinical investigator. Some aspects of this subject have been reviewed, notably with respect to the possible roles of prostaglandins and osteoclast activating factor, with particular reference to breast cancer. There is considerable evidence that the former humoral factor is operative and beginning evidence that the latter may be also. The hope in this continued work is that with better understanding of the mechanisms of hypercalcemia and bone loclization of tumors we will be in a far better position to control and interdict this localization. Images Fig. 3 PMID:898535

  12. [Hypercalcemia of T-cell leukemia in adults].

    PubMed

    Jean-Baptiste, G; Arfi, S; Plumelle, Y; Panelatti, G; Mangin, J L; Pascaline, N

    1993-04-01

    A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells. PMID:8167627

  13. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  14. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  15. Hypercalcemia in critically ill surgical patients.

    PubMed Central

    Forster, J; Querusio, L; Burchard, K W; Gann, D S

    1985-01-01

    Critical surgical illness, commonly accompanied by shock, sepsis, multiple transfusions, and renal failure, is usually associated with low total calcium and/or low or normal ionized calcium. A seminal case of hypercalcemia in a surgical intensive care unit (SICU) patient prompted the review of 100 patients with longer than average SICU days (greater than 12) to determine the incidence, associated factors, and possible etiologies of this condition. Ten patients had elevated measured, and five others had elevated calculated, ionized calcium (5.9 +/- 0.25 mg%), an incidence of 15%. Compared to the 85 patients who did not develop hypercalcemia, this population had a significantly higher frequency of the following: renal failure, dialysis, total parenteral nutrition (TPN) usage greater than 21 days, bacteremic days greater than 1, transfusions greater than 24 units, shock greater than 1 day, SICU days greater than 36, and antibiotics used greater than 7. In addition, this group had significantly more days of hypocalcemia early in their hospital course. There was no difference in sex, age, mortality, or incidence of respiratory failure. Two patients studied in depth had renal failure requiring dialysis and no malignancy, milk-alkali syndrome, hyperthyroidism, or hypoadrenalism. Parathormone (PTH) concentrations were high normal or elevated (N terminal 20 and 21 pg/ml; C terminal 130 microliters Eq/ml and 1009 pg/ml) at the time of elevated calcium (total 9.2 to 14.6 mg%; ionized 4.9 to 8.2 mg%). Immobilization does not increase PTH. In renal failure, PTH elevation is a consequence of hypocalcemia rather than hypercalcemia. Moreover, five patients did not have renal failure. Shock, sepsis, and multiple transfusions containing citrate may lower total and/or ionized calcium and thus stimulate PTH secretion. Whatever the mechanism, approximately 15% of critically ill surgical patients develop hypercalcemia, which may represent a new form of hyperparathyroidism. PMID:3931594

  16. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  17. Denosumab for Treatment of Hypercalcemia of Malignancy

    PubMed Central

    Glezerman, Ilya G.; Leboulleux, Sophie; Insogna, Karl; Gucalp, Rasim; Misiorowski, Waldemar; Yu, Bennett; Zorsky, Paul; Tosi, Diego; Bessudo, Alberto; Jaccard, Arnaud; Tonini, Giuseppe; Ying, Wendy; Braun, Ada; Jain, Rajul K.

    2014-01-01

    Context: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. Objective: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. Design, Setting, and Participants: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening. Intervention: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks. Main Outcome Measures: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study. Results: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reached CSC ≤11.5 mg/dL, and 12 patients (33%) reached CSC ≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%). Conclusions: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM. PMID:24915117

  18. Systemic lupus erythematosus-related hypercalcemia with ectopic calcinosis.

    PubMed

    Zhao, Lidan; Huang, Linfang; Zhang, Xuan

    2016-07-01

    We report a case of a 39-year-old female with active systemic lupus erythematosus who complained of lethargy and weakness with a moderate renal impairment. Hypercalcemia was confirmed by laboratory examination. Her X-ray revealed significant ectopic calcinosis in subcutaneous tissue of bilateral hands, and Tc-99(m) methylene diphosphonate bone scan revealed a remarkably intense uptake of bilateral lungs. She had no evidence suggestive of other diseases related to hypercalcemia such as hyperparathyroidism and malignancy. She had abnormally high serum parathyroid hormone-related protein (PTHrP) which fell to normal after treatment. Glucocorticoid, cyclophosphamide plus calcitonin and etidronate were administered and the patient improved greatly. Literature review demonstrated that lupus-related hypercalcemia with ectopic calcinosis is a rare complication and increased PTHrP is probably one of the main mechanisms. Lung uptake in bone scan may be a special and reliable clue suggestive of hypercalcemia. PMID:27136920

  19. Rhabdomyosarcoma-induced hypercalcemia in a nude mouse.

    PubMed

    Takeuchi, T; Takeuchi, H; Hoshino, R; Ohmi, K

    1982-07-01

    Hypercalcemia in nude mice with a rhabdomyosarcoma transplanted from a hypercalcemic patient is reported. The tumor had been transplanted to nude mice from a 15-year-old girl with hypercalcemia which appeared as the rhabdomyosarcoma developed and metastasized to the peritoneal and pleural cavities. The tumor was successfully transplanted to nude mice, which presented an elevated serum calcium level. No remarkable elevation of serum parathyroid hormone or 1 alpha, 25-dihydroxyvitamin D was found in the mouse with rhabdomyosarcoma. Injection of indomethacin restored the elevated serum calcium level to the normal range. The prostaglandin E2 level was approximately 15 times higher in the tumor-bearing mouse serum than in the control mouse serum. These data indicate that hypercalcemia in this patient can be ascribed to prostaglandin E2 produced by the rhabdomyosarcoma. PMID:6952956

  20. Catastrophic hypercalcemia as a technical complication in home hemodialysis.

    PubMed

    Murlidharan, Praveen; Chan, Christopher T; Bargman, Joanne M

    2011-08-01

    Life-threatening hypercalcemia in dialysis patients is very unusual. We present a case where life-threatening hypercalcemia in a home hemodialysis patient resulted from a technical mistake. A 46-year-old woman, on home nocturnal hemodialysis, presented to the emergency room with history of altered sensorium, vomiting and sweating, which started 1 h after initiation of dialysis the previous night. Serum calcium was 6.5 mmol/L. She improved with 10 h of low-calcium hemodialysis. Investigation revealed that the drain port of the reverse osmosis machine was connected to the dialysis machine and the product water was connected to the drain leading to acute hypercalcemia. PMID:25949494

  1. All-Trans-Retinoic-Acid Unmasking Hypercalcemia of Hyperparathyroidism.

    PubMed

    Yanamandra, Uday; Sahu, Kamal Kant; Khadwal, Alka; Prakash, Gaurav; Varma, Subhash Chander; Malhotra, Pankaj

    2016-06-01

    We present a patient of acute promyelocytic leukaemia managed with all-trans-retinoic-acid and arsenic trioxide who developed hypercalcemia with target organ damage. The patient also was simultaneously discovered to be symptomatic from hyperparathyroidism, which was unmasked after ATRA administration. Patient was successfully managed without any interruption of ATRA therapy and parathyroidectomy. We discuss the mechanisms of ATRA in causing hypercalcemia and its possible role in index case in unmasking hyperparathyroidism. Present case refutes Occam's razor and emphasise that known adverse effects shouldn't withhold clinicians from working up for other common causes for a given condition. PMID:27408352

  2. Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis

    PubMed Central

    Sharmeen, Saika; Kalkan, Esra; Yi, Chunhui; Smith, Steven D.

    2016-01-01

    We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID:26904327

  3. Paraneoplastic hypercalcemia in a dog with thyroid carcinoma

    PubMed Central

    Lane, Amy E.; Wyatt, Kenneth M.

    2012-01-01

    This case report describes a dog with thyroid carcinoma and paraneoplastic hypercalcemia. Following thyroidectomy the dog became hypocalcemic and required supplementation with calcitriol and calcium carbonate. During the following 2 years, attempts to reduce the supplementation resulted in hypocalcemia. The dog died from renal failure with no evidence of thyroid carcinoma. PMID:23543930

  4. [Hypercalcemia in malignancies of the female genital tract].

    PubMed

    Piura, Benjamin

    2008-03-01

    Hypercalcemia is the most common paraneoplastic syndrome in adult malignancies (10%-30%) and rare in pediatric cancers (0.5%-1.3%). Hypercalcemia in malignancies is categorized into two groups: 1) Humoral hypercalcemia of malignancy (HHM)-caused by substances that are produced by the tumor cells and secreted into the blood circulation such as parathyroid hormone-related protein (PTH-rP), parathyroid hormone-intact (PTH-i), the enzyme 1-alpha-hydroxylase that catalyzes the synthesis of the active form of vitamin D (1,25-dihydroxyvitamin D3), and other substances; 2) Hypercalcemia due to bone destruction by metastases. Hypercalcemia occurs in less than 5% of female genital tract malignancies and virtually in all cases (95%) it is HHM. Female genital tract malignancy-associated HHM is caused most often (80%) by PTH-rP. Ovarian cancer is the most common female genital tract malignancy that is associated with HHM. Although HHM occurs in only 5% of ovarian cancers, it occurs in a relatively high percentage in the following rare ovarian tumors: a). Small cell carcinoma of the ovary - a rare tumor that accounts for only 1% of all ovarian cancers and is associated with HHM in 66% of the cases; b). Clear cell carcinoma of the ovary - an uncommon tumor that accounts for 5% of all ovarian cancers and is associated with HHM in 5%-10% of the cases. Since dysgerminoma is the most common malignant ovarian tumor in children, in girls it is the second most common ovarian neoplasm, after ovarian small cell carcinoma, to be associated with HHM. PMID:18488865

  5. Hypercalcemia in a Dog with Chronic Ingestion of Maxacalcitol Ointment.

    PubMed

    Nakamura, Kensuke; Tohyama, Nobuo; Yamasaki, Masahiro; Ohta, Hiroshi; Morishita, Keitaro; Takiguchi, Mitsuyoshi

    2016-01-01

    A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr. PMID:27259026

  6. Hypercalcemia as a Cause of Kidney Failure: Case Report

    PubMed Central

    Stojceva-Taneva, Olivera; Taneva, Borjanka; Selim, Gjulsen

    2016-01-01

    BACKGROUND: Hypercalcemia is a common manifestation in clinical practice and occurs as a result of primary hyperparathyroidism, malignancy, milk-alkali syndrome, hyper or hypothyroidism, sarcoidosis and other known and unknown causes. Patients with milk-alkali syndrome typically are presented with renal failure, hypercalcemia, and metabolic alkalosis caused by the ingestion of calcium and absorbable alkali. This syndrome is caused by high intake of milk and sodium bicarbonate. CASE PRESENTATION: We present a 28-year old male admitted to hospital with a one-month history of nausea, vomiting, epigastric pain, increased blood pressure and worsening of renal function with hypercalcemia. His serum PTH level was almost undetectable; he had mild alkalosis, renal failure with eGFR of 42 ml/min, anemia, hypertension and abnormal ECG with shortened QT interval and ST elevation in V1-V4. He had a positive medical history for calcium-containing antacids intake and after ruling out primary hyperparathyroidism, malignancy, multiple myelomas, sarcoidosis, and thyroid dysfunction, it seemed plausible to diagnose him as having the milk-alkali syndrome. CONCLUSION: Although milk-alkali syndrome currently may be more probably a result of calcium and vitamin D intake in postmenopausal women, or in elderly men with reduced kidney function taking calcium-containing medications, one should not exclude the possibility of its appearance in younger patients taking calcium-containing medications and consider it a serious condition taking into account its possibility of inducing renal insufficiency. PMID:27335601

  7. Multiple myeloma with hypercalcemia and chloride resistant metabolic alkalosis.

    PubMed

    Alshayeb, Hala; Patel, Vikul; Naseer, Adnan; Mangold, Therese A; Wall, Barry M

    2011-10-01

    This report describes a novel presentation of chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM). A 51-year-old male with newly diagnosed MM presented with widespread skeletal involvement, calcium (Ca(+2)) of 18 mg/dL, phosphorous (PO4) of 6 mg/dL, serum bicarbonate (HCO3) of 37 mEq/L, and serum creatinine (Cr) of 2.6 mg/dL Other causes of metabolic alkalosis such as vomiting, diuretics, alkali ingestion, mineralocorticoid excess and hypokalemia were excluded. Hypercalcemia and metabolic alkalosis were only partially corrected after rehydration, calcitonin and steroids. Subsequent treatment with zoledronic acid resulted in resolution of hypercalcemia and correction of metabolic alkalosis.The chloride resistant component of metabolic alkalosis was most likely related to extensive release of Ca(+2), carbonate and phosphate from bone by activated osteoclasts with inhibited osteoblastic activity. The additional reduction in glomerular filtration rate due to MM, contributed to a triad mimicking Calcium-Alkali syndrome. PMID:22073517

  8. Hypercalcemia and renal failure in the course of sarcoidosis--case report.

    PubMed

    Kempisty, Anna; Kuś, Jan

    2012-01-01

    Disturbances of calcium metabolism such as hypercalcemia or/and hypercalciuria in the course of sarcoidosis can be a cause of renal failure in some patients. Life threatening hypercalcemia in sarcoidosis patients is not very frequent. Severe hypercalcemia leading to renal insufficiency is a very rare condition. We present a case of 53-year old man who was admitted to Department of Lung Diseases because of hypercalcemic syndrome and renal failure, and in whom diagnosis of sarcoidosis was made. He was successfully treated with systemic corticosteroids. In this article we present physiological mechanism of hypercalcemia in sarcoidosis patients, mechanism of renal damage and management of these difficult problems. PMID:23109211

  9. Dangerous nutrition? Calcium, vitamin D, and shark cartilage nutritional supplements and cancer-related hypercalcemia.

    PubMed

    Lagman, Ruth; Walsh, Declan

    2003-04-01

    The use of nutritional supplements in the general population and in cancer patients has become very popular. These supplements are not perceived as medications and are presumed to be safe by cancer patients, who may however be at risk for hypercalcemia. We note that many of our patients who have developed symptomatic hypercalcemia were taking vitamin D, calcium, or shark cartilage supplements. We report eight cases of hypercalcemia in cancer patients seen at the Cleveland Clinic Foundation in whom these nutritional supplements may have contributed to the prevalence or severity of hypercalcemia. PMID:12673461

  10. [Hypercalcemia in sarcoidosis--case report, prevalence, pathophysiology and therapeutic options].

    PubMed

    Ackermann, D

    2007-05-01

    Hypercalcemia is a highly prevalent complication of sarcoidosis. A medical history of a patient with sarcoidosis is shown as case report. Depending on the population studied about 2-63% of sarcoidosis patients show hypercalcemia. The major difference in the prevalence of hypercalcemia may be in part due to the undulating course of subacute sarcoidosis, so hypercalcemia may be missed when serum calcium is not frequently measured. Hypercalciuria appears to be twice as prevalent then hypercalcemia and should be looked for in every sarcoidosis patient. Hypercalcemia in sarcoidosis is due to the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages. 1,25-dihydroxyvitamin D3 leads to an increased absorption of calcium in the intestine and to an increased resorption of calcium in the bone. Immunoregulatory properties have been ascribed to 1,25-dihydroxyvitamin D3. It is an important inhibitor of interleukin-2 and of interferon-gamma-synthesis, two cytokines that are important in granuloma formation in sarcoidosis. It is thought that 1,25-dihydroxyvitamin D3 counterregulates uncontrolled granuloma formation. Treatment of hypercalcemia depends on the serum level of hypercalcemia and its persistence. Generally sarcoidotic patients should be advised to avoid sun exposition to reduce vitamin D3 synthesis in the skin, to omit fish oils that are rich of vitamin D and to produce more than two liters urine a day by adapting fluid intake. Although severe hypercalcemia seems to be rare, glucocorticosteroid treatment should be started if corrected total calcium level rises beyond 3 mmol/l. If hypercalcemia is symptomatic, treatment should be started even at lower levels. Glucocorticosteroids act by inhibition of the overly 1alpha-hydroxylase activity of macrophages. Alternatively, treatment with chloroquine or ketoconazole can be established. If isolated hypercalciuria without hypercalcemia is present with evidence for recurrent nephrolithiasis, patients can be treated

  11. 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

  12. Severe hypercalcemia unmasked by Vitamin D in a patient with sarcoidosis

    PubMed Central

    Nayak-Rao, S

    2013-01-01

    Severe hypercalcemia is uncommon in clinical practice and is usually due to primary hperparathyroidism or malignancy. We present a patient who presented with severe hypercalcemia with renal failure; further evaluation of which revealed the diagnosis of sarcoidosis. This case is presented in view of the rarity of presentation of sarcoidosis with hypercalcemic crisis. PMID:24049278

  13. Hypercalcemia and parathyroid hormone-related protein in a dog with undifferentiated nasal carcinoma.

    PubMed Central

    Anderson, G M; Lane, I; Fischer, J; Lopez, A

    1999-01-01

    Hypercalcemia was discovered in a 7-year-old, castrated male basset hound with a suspected nasal tumor. The dog died the day after admission and nasal carcinoma and disseminated intravascular coagulation were diagnosed on postmortem. Detectable levels of serum PTHrP support a diagnosis of hypercalcemia of malignancy. PMID:10340096

  14. An interesting case of systemic lupus erythematosus presenting with hypercalcemia: A diagnostic dilemma

    PubMed Central

    Abdul Gafor, Abdul Halim; Cader, Rizna Abdul; Das, Srijit; Masir, Noraidah; Wahid, Fadilah Abdul

    2013-01-01

    Background Hypercalcemia is common in primary hyperparathyroidism malignancies and even in tuberculosis. Interestingly, systemic lupus erythematosus (SLE) rarely presents with hypercalcemia. Case Report: We describe an interesting case of SLE in a patient who was otherwise thought to have either tuberculosis or a malignancy. The patient initially presented with feeling unwell, with generalized lymphadenopathy, bilateral pleural effusion, and bilateral corneal calcium deposits secondary to severe hypercalcemia. The diagnosis of SLE was made based on positivity of antinuclear antibodies (ANA) and anti-dsDNA, the presence of serositis, lymphadenopathy, autoimmune hemolytic anemia, and constitutional symptoms. She was treated with steroids, with tremendous improvement in her general well-being, resolution of lymphadenopathy and pleural effusion, and normalization of her hemoglobin and serum calcium. The atypical presentation of SLE with hypercalcemia with pleural effusion is discussed. Conclusions: SLE should be one of the differential diagnoses in patients presenting with severe hypercalcemia. PMID:23569551

  15. A successful treatment of hypercalcemia with zoledronic acid in a 15-year-old boy with acute lymphoblastic leukemia

    PubMed Central

    Park, Hye-Jin; Choi, Eun-Jin

    2016-01-01

    Severe hypercalcemia in children is a rare medical emergency. We present a case of a 15-year-old boy with hypercalcemia (total calcium level, 14.2 mg/dL) with a normal complete blood count, no circulating blasts in the peripheral blood film, and no other signs of acute lymphoblastic leukemia (ALL), including no signs of lymphadenopathy or hepatosplenomegaly. The hypercalcemia was successfully treated with zoledronic acid. As hypercalcemia can be the only presenting symptom of ALL in children, the diagnosis is often delayed. In children presenting with hypercalcemia, malignancies must be considered in the differential diagnosis. PMID:27462588

  16. Case of hypercalcemia secondary to hypervitaminosis a in a 6-year-old boy with autism.

    PubMed

    Vyas, Arpita Kalla; White, Neil H

    2011-01-01

    Vitamin A intoxication secondary to over-the-counter nutritional supplements and from its use in acne treatment has been described. However, there have been very few case reports of chronic hypervitaminosis A leading to hypercalcemia in the pediatric population. This paper describes a boy with hypercalcemia secondary to chronic vitamin A intoxication in the context of vitamin A usage for therapy of autism. In addition to discontinuation of vitamin A, hyperhydration, and furosemide, the hypercalcemia in this patient required the use of prednisone and pamidronate to normalize the calcium. PMID:22937283

  17. 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

  18. 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

  19. [65-year old female patient with persistent hypercalcemia].

    PubMed

    Wiedmann, M; Kassahun, W; Deckert, F; Tröltzsch, M; Sturmvoll, M; Führer, D

    2007-12-01

    A 65-year old patient presented with newly diagnosed hypercalcemia and elevated parathyroid hormone levels. Exploration of parathyroid glands was performed under the diagnosis of primary hyperparathyroidism and was combined with thyreoidectomy due to concomittant multinodular goiter. However, no parathyroid adenoma was identified despite careful exploration. Therefore, the operation was terminated and an ectopic adenoma was suspected. A (99m)Tc-sestamibi scintigraphy with SPECT, neck ultrasound, neck CT scan with contrast media and selective venous sampling were performed for further localization of the adenoma. A single adenoma localized in the submandibular area of the left jaw was suspected and confirmed during surgical reexploration. Postoperatively, parathyroid hormone levels were below detection level and the patient required short-term calcium supplementation for symptomatic hypocalcemia. PMID:17965847

  20. [Subcutaneous fat necrosis in the newborn: a risk for severe hypercalcemia].

    PubMed

    Barbier, C; Cneude, F; Deliège, R; El Kohen, R; Kremy, O; Leclerc, F

    2003-08-01

    Hypercalcemia associated with subcutaneous fat necrosis (SCN) is a well known but rare event in the newborn. A newborn infant with a history of SCN was admitted because of anorexia, adynamia, polyuria and polydipsia at 6 weeks of age. Serum calcium was markedly increased on admission, while it was normal on the first day of life. Evolution was favourable after treatment including isotonic saline solution, furosemide, corticosteroids, calcitonin and a low calcium and vitamin D diet. Hypercalcemia was severe enough to potentially induces fatal complications in this case. Neonates who develop skin lesions consistent with SCN should be followed-up for possible onset of hypercalcemia and treated in due time. The treatment of hypercalcemia in SCN is reviewed. PMID:12922005

  1. A case of hypercalcemia and gastric necrosis from hot pack ingestion.

    PubMed

    Padmanabhan, Pradeep; Spiller, Henry A; Bosse, George M

    2010-06-01

    Hot packs (instant hot compresses) are frequently used to relieve pain. We report a patient who had significant complications from ingestion of a hot pack containing calcium salts. A 35-year-old male swallowed three hot packs, and developed hematemesis, severe abdominal pain, and hypercalcemia (21.1 mg/dl). He developed diffuse gastric necrosis requiring gastrectomy and colonic interposition. Hypercalcemia was treated with intravenous fluids, pamidronate, and calcitonin. A Medline search revealed no prior report on hot pack ingestion though ingestion of calcium salts has been reported. Hot packs can potentially cause significant injury both from an exothermic reaction and hypercalcemia. Ingestions of calcium salts can result in necrosis of the stomach. Management includes aggressive treatment of hypercalcemia, supportive care and upper gastrointestinal endoscopy. PMID:20376594

  2. Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

    ClinicalTrials.gov

    2016-02-18

    Breast Cancer; Hypercalcemia of Malignancy; Colon Cancer; Endocrine Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Metastatic Cancer; Multiple Myeloma; Parathyroid Neoplasms; Renal Cancer; Thyroid Cancer; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Non-Small Cell Lung Cancer

  3. An unexpected cause of severe and refractory PTH-independent hypercalcemia: case report and literature review.

    PubMed

    Rados, Dimitris Varvaki; Furlanetto, Tania Weber

    2015-06-01

    Hypercalcemia is a common condition in the internal medicine practice. Sometimes its cause is not readily apparent, so extensive investigation is appropriate. Here we report an unexpected cause for hypercalcemia in an elderly woman. The case of an 82-years old woman with PTH-independent hypercalcemia, lymphocytosis, normal serum 1,25 (OH)vitamin D levels, and low serum PTHrp levels, is described. Medical history and complementary investigation were unremarkable, except for increased metabolic activity in the glutei regions, as measured by whole body 18F-FDG PET-CT. Reviewing her medical history, her sister recalled that she had been submitted to intramuscular methylmethacrylate injections, for cosmetic purposes, five years before presentation, which was confirmed by muscle biopsy. Low calcium intake, parenteral bisphosphonates, calcitonin, and glucocorticoids were used to control serum calcium levels. Methylmethacrylate injections, used cosmetically, are a new cause for hypercalcemia, even after many years. Hypercalcemia was probably due to calcitriol overproduction in foreign body granulomas. Persistent reactive lymphocytosis could be a clue for this inflammatory cause of hypercalcemia. PMID:26154099

  4. [Primary hyperparathyroidism as a cause of hypercalcemia in a patient with breast cancer].

    PubMed

    Zajícková, Katerina

    2010-01-01

    Hypercalcemia associated with breast cancer arises either from metastatic bone disease or from paraneoplastic secretion of parathyroid hormone-related peptide. We report a female 69-year-old patient with invasive intraductal breast cancer and hypercalcemia (3,4 mmol/l) referred to endocrinologist. Standard care in oncology was refused and with respect to the presence of estrogenic receptors the patient accepted only antiestrogenic treatment. Bone scan revealed no skeletal metastasis. Entry laboratory exam confirmed hypercalcemia, hypophosphatemia and significantly elevated parathyroid hormone (793 ng/l). The patient complained of bone pain and dyspepsia. Neck ultrasound showed a multinodular goiter with particularly enlarged left lobe. Parathyroid gland scintigraphy revealed a possible parathyroid adenoma behind the lower pole of the left thyroid lobe. The patient underwent thyroidectomy with an excision of the parathyroid mass. Microscopic examination identified a benign adenomatous goitre and benign parathyroid adenoma. Postoperatively, both serum calcium and parathyroid hormone normalized. Replacement of calcium and vitamin D were initiated both with bisphosphonate with regard to newly diagnosed osteoporosis. This case demonstrates a patient with breast cancer and hypercalcemia unrelated to the malignant disease. Primary hyperparathyroidism should be considered as a possible cause of hypercalcemia in breast cancer patients in the setting of negative bone scan, elevated parathyroid hormone and mildly deteriorated bone mineral density. PMID:21391355

  5. Prevalence of hypercalcemia among cancer patients in the United States.

    PubMed

    Gastanaga, Victor M; Schwartzberg, Lee S; Jain, Rajul K; Pirolli, Melissa; Quach, David; Quigley, Jane M; Mu, George; Scott Stryker, W; Liede, Alexander

    2016-08-01

    Hypercalcemia of malignancy (HCM) is a serious metabolic complication whose population-based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were ≥18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009-2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]-10.2% [2010]), lowest for prostate cancer (1.4% [2012]-2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0-2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five-year study period. PMID:27263488

  6. Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of Sarcoidosis

    PubMed Central

    Sharma, Neeraj; Tariq, Hassan; Uday, Kalpana; Skaradinskiy, Yevgeniy; Niazi, Masooma; Chilimuri, Sridhar

    2015-01-01

    We discuss a case of a 61-year-old woman who presented with substernal chest pain. She was found to have elevated calcium levels, anemia, and acute kidney injury. The hypercalcemia persisted despite therapy with fluids and bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial impression was likely underlying hematologic malignancy such as lymphoma or multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing granulomatous inflammation. Further workup revealed elevated vitamin 1,25 dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast computed tomography (CT) scan of chest showed bilateral apical bronchiectasis, but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing granulomatous inflammation consistent with sarcoidosis. After initiating glucocorticoid therapy, the patient's hypercalcemia improved and her kidney function returned to baseline. PMID:26199627

  7. Hypercalcemia of malignancy associated with renal cell carcinoma in a dog.

    PubMed

    Merrick, Christine H; Schleis, Stephanie E; Smith, Annette N; Mallett, Courtney L; Graff, Emily C; Johnson, Calvin

    2013-01-01

    A 10 yr old castrated male Siberian husky was evaluated for polyuria, polydipsia, a retroperitoneal mass, and urolithiasis. A marked elevation in Ca was noted on initial blood work, and results of additional testing were consistent with hypercalcemia of malignancy, including an elevated parathyroid hormone-related peptide (PTHrp) value. Based on clinical signs, blood work, diagnostic imaging, and cytology results, unilateral renal neoplasia was suspected. Following a complete right nephrectomy and cystotomy, histopathologic examination confirmed a diagnosis of renal cell carcinoma (RCC). Five days postoperatively, the hypercalcemia had nearly resolved and the PTHrp was zero. This is the first reported case of hypercalcemia of malignancy associated with RCC in a dog. PMID:23861266

  8. Hypophosphatasia Presenting with Pyridoxine-Responsive Seizures, Hypercalcemia, and Pseudotumor Cerebri: Case Report

    PubMed Central

    Alanay, Yasemin; Alikaşifoğlu, Ayfer; Topçu, Meral; Mornet, Etienne; Özön, Alev; Kandemir, Nurgün

    2012-01-01

    Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. Key words: Hypophosphatasia, pyridoxine-responsive seizures, bisphosphonates, alkaline phosphatase, bone resorption, hypercalcemia Conflict of interest:None declared. PMID:22394703

  9. Carcinoma of Lung with Adrenal Hyperfunction and Hypercalcemia Treated by Parathyroidectomy

    PubMed Central

    Gault, M. Henry; Kinsella, T. Douglas

    1965-01-01

    A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered. PMID:14243867

  10. Hypercalcemia from metastatic pancreatic neuroendocrine tumor secreting 1,25-dihydroxyvitamin D

    PubMed Central

    Zhu, Viola; de las Morenas, Antonio; Janicek, Milos

    2014-01-01

    Malignant hypercalcemia occurs in about 20-30% of patients with cancer, both solid tumors and hematologic malignancies. The secretion of parathyroid hormone-related protein (PTH-rP) is the most common cause and has been shown to be the etiology of hypercalcemia associated with neuroendocrine tumors. Here we report the case of a patient with metastatic pancreatic neuroendocrine tumor who developed hypercalcemia more than 4 years after the initial diagnosis as a result of secretion of 1,25-dihydroxyvitamin D, a mechanism only commonly seen in lymphomas. The successful control of the patient’s disease with capecitabine and temozolomide led to the alleviation of this paraneoplastic syndrome. PMID:25083313

  11. “Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D

    PubMed Central

    Pandita, Kamal Kishore; Razdan, Sushil; Kudyar, Rattan Parkash; Beigh, Aadil; Kuchay, Shafi; Banday, Tanveer

    2012-01-01

    Summary Vitamin D is increasingly recognized to have several beneficial effects. Its toxicity, causing hypercalcemia, is considered as extremely rare. We report case series of 15 patients (most of them being elderly subjects) with iatrogenic symptomatic hypercalcemia in whom toxicity occurred due to empirical excessive administration of vitamin D by oral and parenteral route. PMID:23087723

  12. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Idiopathic infantile hypercalcemia (IIH) is a disorder the genetic etiology and physiological basis of which are not well understood. The objective of the study was to describe the underlying physiology and genetic cause of hypercalcemia in an infant with severe IIH and to extend these genetic findi...

  13. Ketotic Hypercalcemia: A Case Series and Description of a Novel Entity

    PubMed Central

    Hawkes, Colin Patrick

    2014-01-01

    Context: The ketogenic diet is increasingly used in refractory epilepsy and is associated with clinically significant effects on bone and mineral metabolism. Although hypercalciuria and loss of bone mineral density are common in patients on the ketogenic diet, hypercalcemia has not previously been described. Objective: The aim of the study was to describe three children who developed hypercalcemia while on the ketogenic diet. Design: A retrospective chart review of three children on the ketogenic with severe hypercalcemia was conducted. Results: We describe three children on the ketogenic diet for refractory seizures who presented with hypercalcemia. Case 1 was a 5.5-year-old male with an undiagnosed, rapidly progressive seizure disorder associated with developmental regression. Case 2 was a 2.5-year-old male with a chromosomal deletion of 2q24.3, and case 3 was a 4.6-year-old male with cerebral cortex dysplasia. Patients had been on a ketogenic diet for 6 to 12 months before presentation. Daily intake of calcium and vitamin D was not excessive, and all three patients were not acidotic because they were taking supplemental bicarbonate. Each child had elevated serum levels of calcium and normal serum phosphate levels, moderately elevated urinary calcium excretion, and low levels of serum alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D. All patients responded to calcitonin. Conclusions: Hypercalcemia is an uncommon complication of the ketogenic diet, and these children may represent the severe end of a clinical spectrum of disordered mineral metabolism. The mechanism for hypercalcemia is unknown but is consistent with excess bone resorption and impaired calcium excretion. PMID:24606099

  14. 1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma

    PubMed Central

    2014-01-01

    Background Seminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied. The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma. Case presentation A 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed “cannon ball” pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively. Conclusion The association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values. PMID:24721620

  15. Hypercalcemia due to latrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat.

    PubMed

    Smith, Stephanie A; Freeman, Lisa C; Bagladi-Swanson, Mary

    2002-01-01

    A 9-year-old, spayed female domestic shorthair cat presented for polyphagia, polydipsia, and polyuria following chronic methylprednisolone acetate therapy for pruritus. Initial diagnostics were consistent with uncomplicated diabetes mellitus. Serum calcium was within reference range. Within 12 hours the cat developed depression, anorexia, vomiting, and severe dehydration. Laboratory analysis indicated marked hypercalcemia as measured by both ionized and total calcium concentration. No underlying neoplastic or inflammatory process was identified. An adrenocorticotropic hormone stimulation test was indicative of adrenocortical insufficiency. The hypercalcemia resolved with glucocorticoid supplementation and correction of the dehydration. The diabetes mellitus and adrenal insufficiency both resolved within 9 weeks. PMID:11804313

  16. Case Report: Severe Hypercalcemia Mimicking St-Segment Elevation Myocardial Infarction

    PubMed Central

    Schutt, Robert C.; Bibawy, John; Elnemr, Mina; Lehnert, Amy L.; Putney, David; Thomas, Anusha S.; Barker, Colin M.; Pratt, Craig M.

    2014-01-01

    The identification of ST-segment elevation on the electrocardiogram is an integral part of decision making in patients who present with suspected ischemia. Unfortunately, ST-segment elevation is nonspecific and may be caused by noncardiac causes such as electrolyte abnormalities. We present a case of ST-segment elevation secondary to hypercalcemia in a patient with metastatic cancer. PMID:25574349

  17. Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis

    PubMed Central

    Belmont, John W; Reid, Barbara; Taylor, William; Baker, Susan S; Moore, Warren H; Morriss, Michael C; Podrebarac, Susan M; Glass, Nancy; Schwartz, I David

    2002-01-01

    Background Disaccharide Intolerance Type I (Mendelian Interance in Man database: *222900) is a rare inborn error of metabolism resulting from mutation in sucrase-isomaltase (Enzyme Catalyzed 3.2.1.48). Usually, infants with SI deficiency come to attention because of chronic diarrhea and nutritional evidence of malabsorption. Case Presentation We describe an atypical presentation of this disorder in a 10-month-old infant. In addition to chronic diarrhea, the child displayed severe and chronic hypercalcemia, the evaluation of which was negative. An apparently coincidental right orbital hemangioma was detected. Following identification of the SI deficiency, an appropriately sucrose-restricted, but normal calcium diet regimen was instituted which led to cessation of diarrhea, substantial weight gain, and resolution of hypercalcemia. Conclusions This case illustrates that, similar to congenital lactase deficiency (Mendelian Interance in Man database: *223000, Alactasia, Hereditary Disaccharide Intolerance Type II), hypercalcemia may complicate neonatal Sucrase-Isomaltase deficiency. Hypercalcemia in the presence of chronic diarrhea should suggest disaccharide intolerance in young infants. PMID:12014995

  18. Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma.

    PubMed

    Jain, Ankur; Malhotra, Pankaj; Prakash, Gaurav; Varma, Subhash; Kumar, Narender; Das, Asim

    2016-06-01

    Clinicians in hematology practice commonly encounter anemia, hypercalcemia and renal failure, which when present in combination evoke a diagnostic workup for multiple myeloma. We report a 71-years old lady who presented to our hematology clinic with fever and easy fatiguability of 3 months duration and on investigations was found to have anemia and hypercalcemia. Direct Coomb's test characterized the anemia as complement mediated (anti-C3d) hemolysis. Biochemical investigations revealed normal 25(OH) Vitamin D3 and suppressed Parathormone levels and a negative workup for plasma cell dyscrasias, sarcoidosis and autoimmune disorders. CT scan revealed a paravertebral mass with cervical, supraclavicular and abdominal lymphadenopathy along with splenomegaly and left pleural effusion. Biopsy from the paravertebral mass confirmed the diagnosis of Hodgkin's disease (nodular sclerosis) using immunohistochemistry. Bone marrow examination suggested infiltration by lymphoma. Hypercalcemia was managed with saline and zoledronic acid. Administration of prednisolone (1 mg/kg/day) along with chemotherapy (ABVD regimen) led to normalization of calcium and hemoglobin levels. However, hemolysis recurred 2 weeks later and hence, Rituximab (375 mg/m(2)) was administered on a weekly schedule for 4 doses and ABVD (2 weekly) was continued, which brought hemolysis under control. Co-occurrence of two paraneoplastic manifestations (complement mediated hemolytic anemia and hypercalcemia) in Hodgkin's lymphoma is very unusual. Present report aims not only to highlight a rare presentation of Hodgkin's lymphoma but also focus on the role of Rituximab in controlling hemolysis associated with this disease. PMID:27408382

  19. Calcitriol-mediated hypercalcemia in a patient with bilateral adrenal non-Hodgkin's B-cell lymphoma case report

    PubMed Central

    Abaroa-Salvatierra, Ana; Shaikh, Bilal; Deshmukh, Mrunalini; Alweis, Richard; Patel, Arti

    2016-01-01

    Calcitriol-mediated hypercalcemia is a frequent manifestation of hematological malignancies. However, there are a few reports of cases presenting with increased angiotensin-converting enzyme (ACE) level, which suggests a possible mechanism similar to that of granulomatous diseases. We present a patient with hypercalcemia, normal parathyroid hormone, and parathyroid hormone-related protein levels but high calcitriol and ACE levels that, after further investigation, was diagnosed with bilateral adrenal non-Hodgkin's B-cell lymphoma. Primary adrenal lymphoma represents only 1% of all non-Hodgkin's lymphomas and is usually asymptomatic but should be considered by clinicians among the malignancies that cause calcitriol-mediated hypercalcemia. PMID:27124160

  20. 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

  1. Life-Threatening Hypercalcemia Revealing Diffuse and Isolated Acute Sarcoid-Like Myositis: A New Entity? (A Case-Series).

    PubMed

    Mageau, Arthur; Rigolet, Aude; Benali, Khadija; Chauchard, Maria; Ladjeroud, Salima; Mahe, Isabelle; Maisonobe, Thierry; Chauveheid, Marie-Paule; Papo, Thomas; Sacre, Karim

    2016-03-01

    Up to 50% patients with sarcoidosis display extra-pulmonary disease. However, initial and isolated (ie, without lung disease) acute muscular involvement associated with pseudo-malignant hypercalcemia is very uncommon. We report on 3 cases of life-threatening hypercalcemia revealing florid and isolated acute sarcoid-like myositis.All patients complained of fatigue, progressive general muscle weakness, and weight loss. Laboratory tests showed a severe life-threatening hypercalcemia (>3.4 mmol/L). Hypercalcemia was associated with increased serum level of 1,25-(OH)2 vitamin D and complicated with acute renal failure. One patient displayed acute pancreatitis due to hypercalcemia.In all cases, PET-scan, performed for malignancy screening, incidentally revealed an intense, diffuse, and isolated muscular fluorodeoxyglucose (FDG) uptake consistent with diffuse non-necrotizing giant cells granulomatous myositis demonstrated by muscle biopsy. Of note, creatine phosphokinase blood level was normal in all cases. No patients displayed the usual thoracic features of sarcoidosis.All patients were treated with high dose steroids and achieved rapid, complete, and sustained remission. A review of English and French publications in Medline revealed 5 similar published cases.Steroid-sensitive acute sarcoid-like myositis causing high calcitriol levels and life-threatening hypercalcemia should be recognized as a separate entity. PMID:26962842

  2. [Abnormal synthesis of 1,25-dihydroxyvitamin D and hypercalcemia in children with tuberculosis].

    PubMed

    Saggese, G; Bertelloni, S; Baroncelli, G I; Fusaro, C; Gualtieri, M

    1989-01-01

    Three children with tuberculosis and hypercalcemia are reported. Before antitubercular treatment 1,25-dihydroxyvitamin D serum levels and urinary calcium excretion were elevated for age in all patients; vitamin D and 25-hydroxyvitamin D were in normal range whereas serum intact parathyroid hormone concentrations were suppressed. Low calcium diet and antitubercular treatment caused a normalization of serum calcium levels and urinary calcium excretion; 1,25-dihydroxyvitamin D concentrations returned in normal range after three months of antituberculosis therapy. When 1,25-dihydroxyvitamin D was normal, a reintroduction of a diet with normal calcium content did not determine new hypercalcemic episodes. These data suggest that an abnormal 1,25-dihydroxyvitamin D production sustains the hypercalcemia of children with tuberculosis. An ectopic and unregulated synthesis of 1,25-dihydroxyvitamin D by macrophages of granulomatous tissue is proposed. PMID:2631059

  3. Hypophosphatasia presenting with pyridoxine-responsive seizures, hypercalcemia, and pseudotumor cerebri: case report.

    PubMed

    Demirbilek, Hüseyin; Alanay, Yasemin; Alikaşifoğlu, Ayfer; Topçu, Meral; Mornet, Etienne; Gönç, Nazlı; Özön, Alev; Kandemir, Nurgün

    2012-03-01

    Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. PMID:22394703

  4. Production of hypercalcemia in the chick embryo by an extract of Solanum malacoxylon.

    PubMed

    Narbaitz, R; Carrillo, B J

    1976-12-01

    White Leghorn eggs were injected on the 15th day of incubation with various doses of an acqueous extract of Solanum malacoxylon (SME). Most of the embryos died after the injection of 0.2 ml but the dose of 0.1 ml was well tolerated. The concentration of calcium in the sera from 15-day embryos injected with 0.1 ml SME was determined. Three hr after the injection the concentration of calcium had increased significantly; this increase lasted for at least 3 hr more but had disappeared 12 hr after the injection. It is suggested that this hypercalcemia may be produced by a water-soluble analog of 1,25-(OH)2D3 the presence of which has been demonstrated in the SME by other authors. It is also assumed that the mortality produced by the higher doses may be related to the hypercalcemia. PMID:1030814

  5. Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

    PubMed Central

    Tse, Gary; Sun, Bing; Wong, Sheung Ting; Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals. PMID:27588173

  6. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children

    PubMed Central

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  7. Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children.

    PubMed

    Martins, Andreia Luís; Moniz, Marta; Nunes, Pedro Sampaio; Abadesso, Clara; Loureiro, Helena Cristina; Duarte, Ximo; Almeida, Helena Isabel

    2015-01-01

    Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life. PMID:26761480

  8. Reversal of Severe and Refractory Humoral Hypercalcemia With 177Lu-Octreotate Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumor of the Pancreas.

    PubMed

    Iliuta, Ioan-Andrei; Beauregard, Jean-Mathieu; Couture, Félix; Douville, Pierre; Mac-Way, Fabrice

    2015-09-01

    A 48-year-old Caucasian male patient with newly diagnosed neuroendocrine tumor of the pancreas with multiple liver metastases developed severe and refractory hypercalcemia. Complementary investigations were compatible with humoral hypercalcemia with high parathyroid hormone-related peptide (PTHrP) levels. Hypercalcemia was refractory to medical treatments for more than 2 years. Serum calcium returned to normal values only after 4 cycles of peptide receptor radionuclide therapy with Lu-octreotate, with concomitant reduction of PTHrP level and tumor regression. The use of radionuclide therapy could be an option for the management of severe humoral hypercalcemia in patients with inoperable metastatic pancreatic neuroendocrine tumor. PMID:26053724

  9. Vitamin D toxicity presenting as hypercalcemia and complete heart block: An interesting case report

    PubMed Central

    Garg, G; Khadgwat, R; Khandelwal, D; Gupta, N

    2012-01-01

    Vitamin D deficiency is widely prevalent across the globe. This has lead to widespread use of vitamin D supplements in populations. We present our experience of vitamin D toxicity in a subject resulting in hypercalcemia and CHB (Complete Heart Block). A 70-year-old female, known hypertensive for thirty five years and diabetic for seven years underwent total knee replacement (TKR) for osteoarthritis left knee in December 2010. For perioperative glycemic control, multiple subcutaneous injections of insulin were advised. Patient later presented with poor glycemic control, decreased appetite and constipation for last 1 month with history of episodes of transient loss of consciousness for 15 days and recurrent vomiting. Biochemical work-up showed hypercalcemia (Serum calcium 12.4 mg/dL). Sr. albumin, ALP, Sr. phosphorus and PTH levels were normal, thus suggesting PTH independent hypercalcemia. Strong suspicion led us to check vitamin D levels in dilution which were 2016 ng/mL, thus confirming vitamin D toxicity. Retrospective analysis of treatment history revealed patient receiving 4 injections of Architol (6 Lac units im) prior to presentation. Work-up for malignancy was negative, brain imaging and EEG were normal. Holter was suggestive of intermittent CHB. Patient was given hydration, injection calcitonin 100 I.U. subcutaneously, injection pamidronate 60 mg infusion, with serum calcium levels normalizing, with relief in constipation, vomiting and behavioral improvement. However, persistence of rhythm disturbances led to permanent pacemaker placement. The present case highlights the dangers of indiscriminate vitamin D usage, exposing patients to potentially life threatening complications. PMID:23565451

  10. An unusual case of hypercalcemia in a patient of concomitant hypoparathyroidism and celiac disease

    PubMed Central

    Somani, Shrikant; Kotwal, Narendra; Upreti, Vimal

    2016-01-01

    Summary Milk alkali syndrome has shown resurgence with increase in use of (prescription or non prescription) calcium supplements. Cases of iatrogenic vitamin D intoxication has also increased due to increasing use of high doses of injectable vitamin D formulations by physicians, surgeons, orthopaedicians, gynecologists and other specialties inadvertently. Here, we present an unusual case of a 17-year-old boy who presented with iatrogenic hypercalcemia as a result of combination of milk alkali syndrome with vitamin D intoxication despite being a case of hypoparathyroidism and concomitantly suffering from celiac disease. PMID:27252747

  11. Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride.

    PubMed

    Sloand, James A; Shelly, Mark A

    2006-11-01

    An underrecognized side effect of long-term lithium carbonate therapy is hyperparathyroidism with associated hypercalcemia and hypocalciuria. Because cessation of lithium carbonate therapy usually does not correct the hyperparathyroidism and associated hypercalcemia, parathyroidectomy frequently is necessary. This is the initial report of 2 patients with lithium carbonate-induced hyperparathyroidism treated with cinacalcet hydrochloride (HCl), which normalized serum calcium levels and reduced intact parathyroid hormone (iPTH) secretion. The patients, both with bipolar disease and a 15- to 30-year history of lithium carbonate therapy, were evaluated for stage 3 chronic kidney disease, persistent hypercalcemia, and hyperparathyroidism. A 67-year-old woman was administered cinacalcet HCl, 30 mg/d, for 11 months. Mean serum calcium level decreased from 10.8 +/- 0.4 mg/dL (2.69 +/- 0.10 mmol/L) to 9.9 +/- 0.4 mg/dL (2.47 +/- 0.10 mmol/L; P < 0.001), and iPTH level decreased from 139 +/- 31 pg/mL (139 +/- 31 ng/L) to 114 +/- 39 pg/mL (114 +/- 39 ng/L; P = not significant). A 63-year-old man was administered 30 mg/d of cinacalcet HCl for 8 months, then 60 mg/d for another 2 months. Mean serum calcium and iPTH levels decreased from 11.0 +/- 0.5 mg/dL (2.74 +/- 0.12 mmol/L) to 10.3 +/- 0.4 mg/dL (2.57 +/- 0.10 mmol/L; P < 0.001) and 138 +/- 10 pg/mL (138 +/- 10 ng/L) to 73 +/- 7 pg/mL (73 +/- 7 ng/L; P = 0.03), respectively. Urinary fractional excretion of calcium was low for both patients before (<0.026 and <0.015) and after (0.026 and 0.008) treatment with cinacalcet HCl. These findings suggest that cinacalcet HCl can provide an alternative nonsurgical means to control this disorder in patients with hypercalcemia of variable severity for whom surgical treatment is not a consideration because of perceived mildness of disease or unsuitability of the patient for surgical intervention. PMID:17060004

  12. An unusual case of hypercalcemia in a patient of concomitant hypoparathyroidism and celiac disease.

    PubMed

    Somani, Shrikant; Kotwal, Narendra; Upreti, Vimal

    2016-01-01

    Milk alkali syndrome has shown resurgence with increase in use of (prescription or non prescription) calcium supplements. Cases of iatrogenic vitamin D intoxication has also increased due to increasing use of high doses of injectable vitamin D formulations by physicians, surgeons, orthopaedicians, gynecologists and other specialties inadvertently. Here, we present an unusual case of a 17-year-old boy who presented with iatrogenic hypercalcemia as a result of combination of milk alkali syndrome with vitamin D intoxication despite being a case of hypoparathyroidism and concomitantly suffering from celiac disease. PMID:27252747

  13. Hypercalcemia and altered biochemical bone markers in post-bone marrow transplantation osteopetrosis: a case report and literature review.

    PubMed

    Kulpiya, Alisa; Mahachoklertwattana, Pat; Pakakasama, Samart; Hongeng, Suradej; Poomthavorn, Preamrudee

    2012-08-01

    Autosomal recessive osteopetrosis is a rare disorder of bone resorption defect that results in generalized sclerotic bones and bone marrow failure. Allogeneic BMT is the only treatment for cure. One of the complications following a successful BMT is hypercalcemia that is a unique complication in this group of patients. We report a three-yr-old boy with osteopetrosis who developed hypercalcemia following the successful BMT. His maximal calcium level was 13.3 mg/dL. Markedly increased both bone formation and resorption markers were demonstrated along with hypercalcemia. These findings indicated an active donor-derived osteoclastic function and thus bone resorption following the successful donor engraftment in the patient. Treatment with hyperhydration, furosemide and bone resorption inhibitors, calcitonin, and bisphosphonate led to normalization of the serum calcium level. Bone resorption but not bone formation marker was persistently elevated despite having normocalcemia during a 16.5-month follow-up period. PMID:21323826

  14. Life-Threatening Hypercalcemia due to Graves' Disease and Concomitant Adrenal Failure: A Case Report and Review of the Literature

    PubMed Central

    Ozkaya, Hande Mefkure; Keskin, Fatma Ela; Haliloglu, Ozlem Asmaz; Senel, Tugba Elif; Kadioglu, Pinar

    2015-01-01

    A 47-year-old woman presented with the complaints of nausea, vomiting, and weight loss. She had a history of bilateral surrenalectomy due to Cushing's syndrome. On examination she had tachycardia and orthostatic hypotension. Laboratory examinations revealed hypercalcemia and suppressed parathyroid hormone levels. She also had thyrotoxicosis due to Graves' disease. The investigations to rule out a malignancy were negative. With steroid, zoledronic acid, and antithyroid drug treatment her symptoms were resolved and calcium level was normalized. This case highlights the importance of recognizing thyrotoxicosis and concomitant adrenal failure as a possible cause of severe hypercalcemia. PMID:25878906

  15. Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcemia.

    PubMed Central

    Warrell, R P; Bockman, R S; Coonley, C J; Isaacs, M; Staszewski, H

    1984-01-01

    Approximately two-thirds of patients who receive the anticancer drug gallium nitrate develop mild hypocalcemia. To evaluate the mechanism of drug-induced hypocalcemia, we tested the effects of gallium nitrate upon in vitro release of 45Ca++ from explanted fetal rat bones. The drug significantly inhibited 45Ca++ release in response to stimulation with both parathyroid hormone and a lymphokine preparation with osteoclast activating factor activity. The inhibitory effects on bone resorption were both time- and dose-dependent. Later, in a pilot study, we treated 10 patients who had cancer-related hypercalcemia with gallium nitrate administered by continuous infusion. All patients responded by a reduction of total serum calcium to normal or subnormal concentrations (13.8 +/- 1.05 mg/dl, mean +/- SD pretreatment, to 8.03 +/- 1.03 mg/dl, mean posttreatment nadir). Our results indicate that gallium nitrate effectively treats cancer-related hypercalcemia and that it probably acts by inhibiting calcium release from bone. Images PMID:6715548

  16. Hypercalcemia - discharge

    MedlinePlus

    ... J. Martin, MD, MPH, ABIM Board Certified in Internal Medicine and Hospice and Palliative Medicine, Atlanta, GA. Also ... URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  17. Severe Hypercalcemia in a Child With Acute Lymphoblastic Leukemia Relapse: Successful Management With Combination of Calcitonin and Bisphosphonate.

    PubMed

    Tagiyev, Anar; Demirbilek, Huseyin; Tavil, Betul; Buyukyilmaz, Gonul; Gumruk, Fatma; Cetin, Mualla

    2016-04-01

    Hypercalcemia is a rare complication of hematological malignancy in children. An 8-year-old girl with CALLA (+) Pre-B-cell ALL developed hypercalcemia during bone marrow relapse. She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L. Rehydration with 0.9% saline and furosemide and methylprednisolone (MP) treatment were used for the treatment of hypercalcemia. The serum ionized calcium level increased to 2.2 mmol/L despite hydration, furosemide, and MP treatment. Then, a single-dose pamidronate (1 mg/kg/dose) was administered. Despite pamidronate treatment, the calcium level continued to rise. Next, calcitonin at a dose of 8 IU/kg/dose, 4 doses per day, was added to the treatment. After commencement of calcitonin treatment, her ionized calcium level decreased to normal reference ranges. In conclusion, because of the postponed effect of bisphosphonate treatment, pamidronate and calcitonin combination is an effective treatment option in the early resolution of malignancy-related hypercalcemia. PMID:26907650

  18. Forearm bone mineral density in familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a comparative study.

    PubMed

    Isaksen, Troels; Nielsen, Christian Stoltz; Christensen, Signe Engkjær; Nissen, Peter H; Heickendorff, Lene; Mosekilde, Leif

    2011-10-01

    Studies have shown that cancellous bone is relatively preserved in primary hyperparathyroidism (PHPT), whereas bone loss is seen in cortical bone. Familial hypocalciuric hypercalcemia (FHH) patients seem to preserve bone mineral in spite of hypercalcemia and often elevated plasma parathyroid hormone (PTH). The objective of this study was to compare total and regional forearm bone mineral density (BMD) in patients with PHPT and FHH and to examine if differences can be used to separate the two disorders. We included 63 FHH, and 121 PHPT patients in a cross-sectional study. We performed dual-energy X-ray absorptiometry scans of the forearm, hip and lumbar spine and measured a number of biochemical variables. PTH patients had significantly lower Z-scores in all parts of the forearm compared to FHH. This was also the case after adjustment for body mass index. When stratifying for age, gender and PTH, T-scores were still significantly lower in PHPT patients than in FHH patients at the total, the mid and the ultradistal forearm, but not at the proximal 1/3 forearm. In a multiple regression analysis BMD Z-score was lower in PHPT compared to FHH at the total forearm, the mid forearm and the ultradistal forearm but not the proximal forearm when adjusting for biochemical variables including PTH, 1,25(OH)(2)D and Ca(2+). These observations support that inactivating mutations in the CASR gene in bone cells in FHH may protect against forearm bone loss. Differences between the two groups in total or regional forearm BMD were inferior to the calcium/creatinine clearance ratio as a diagnostic tool to separate FHH from PHPT. PMID:21785908

  19. Neonatal hypercalcemia secondary to subcutaneous fat necrosis successfully treated with pamidronate: a case series and literature review.

    PubMed

    Samedi, Veronica Mugarab; Yusuf, Kamran; Yee, Wendy; Obaid, Hala; Al Awad, Essa Hamdan

    2014-11-01

    Subcutaneous fat necrosis (SCFN) is a noninfectious panniculitis that occurs in term infants who experience significant distress in the 1st weeks of life, including hypoxic ischemic encephalopathy (HIE). Since the introduction of therapeutic hypothermia for HIE, there have been a few published case reports of SCFN, following this modality of treatment. Although, most cases of SCFN resolve spontaneously, SCFN may be associated with hypercalcemia, which may sometimes reach dangerous levels. Approaches used for the management of this potentially life-threatening condition, include hyperhydration, calciuric diuretics, corticosteroids, and in more resistant cases pamidronate, a bisphosphonate. We report our experience on the use of pamidronate in two cases of severe hypercalcemia associated with SCFN following therapeutic hypothermia for HIE. We believe that with increasing use of therapeutic hypothermia for HIE, clinicians are likely to encounter this condition more frequently. PMID:25452891

  20. Neonatal Hypercalcemia Secondary to Subcutaneous Fat Necrosis Successfully Treated with Pamidronate: A Case Series and Literature Review

    PubMed Central

    Samedi, Veronica Mugarab; Yusuf, Kamran; Yee, Wendy; Obaid, Hala; Al Awad, Essa Hamdan

    2014-01-01

    Subcutaneous fat necrosis (SCFN) is a noninfectious panniculitis that occurs in term infants who experience significant distress in the 1st weeks of life, including hypoxic ischemic encephalopathy (HIE). Since the introduction of therapeutic hypothermia for HIE, there have been a few published case reports of SCFN, following this modality of treatment. Although, most cases of SCFN resolve spontaneously, SCFN may be associated with hypercalcemia, which may sometimes reach dangerous levels. Approaches used for the management of this potentially life-threatening condition, include hyperhydration, calciuric diuretics, corticosteroids, and in more resistant cases pamidronate, a bisphosphonate. We report our experience on the use of pamidronate in two cases of severe hypercalcemia associated with SCFN following therapeutic hypothermia for HIE. We believe that with increasing use of therapeutic hypothermia for HIE, clinicians are likely to encounter this condition more frequently. PMID:25452891

  1. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

    PubMed

    Schlingmann, Karl P; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A M; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J; Rust, Stephan; Forster, Ian C; Hernando, Nati; Jones, Glenville; Wagner, Carsten A; Konrad, Martin

    2016-02-01

    Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

  2. Endogenous prostaglandin E2 mediates inhibition of rat thick ascending limb Cl reabsorption in chronic hypercalcemia.

    PubMed Central

    Peterson, L N; McKay, A J; Borzecki, J S

    1993-01-01

    The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC. Images PMID:8390479

  3. Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

    PubMed

    Atuk, N O; McDonald, T; Wood, T; Carpenter, J T; Walzak, M P; Donaldson, M; Gillenwater, J Y

    1979-05-01

    Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the

  4. Hypercalcemia and diffuse osteolytic lesions in a 45-year-old patient with myeloid sarcoma with megakaryocytic differentiation

    PubMed Central

    Goud, Aditya; Abdelqader, Abdelhai; Dahagam, Chanukya; Jabaji, Ramez; Kumar, Pallavi; Aboulafia, Albert; Selinger, Stephen

    2016-01-01

    Acute megakaryocytic leukemia is a rare form of acute myeloid leukemia that carries a poor prognosis. As most cases of osteolytic lesions are due to plasma cell and myeloid malignancies, maintaining a broad differential directly influences clinical course. We document a 45-year-old patient with progressive constitutional symptoms, osteolytic bone lesions in the setting of hypercalcemia, who developed acutely worsening pancytopenia. The diagnosis of myeloid sarcoma with megakaryocytic differentiation was made after obtaining tissue from osteolytic bone that stained strong for CD34. Immunohistochemical testing underscores the importance of how serologic and urine testing remains limited and can delay early diagnosis in this disease. PMID:27124159

  5. MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS).

    PubMed

    Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R

    2015-09-01

    A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure. PMID:26352981

  6. Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease.

    PubMed

    Iwakura, Takamasa; Ohashi, Naro; Tsuji, Naoko; Naito, Yoshitaka; Isobe, Shinsuke; Ono, Masafumi; Fujikura, Tomoyuki; Tsuji, Takayuki; Sakao, Yukitoshi; Yasuda, Hideo; Kato, Akihiko; Fujiyama, Toshiharu; Tokura, Yoshiki; Fujigaki, Yoshihide

    2013-05-01

    An 86-year-old man, diagnosed as having mycosis fungoides in May 2008 and treated with repeated radiation therapy, was admitted to our hospital for initiation of hemodialysis due to end-stage renal disease (ESRD) in April 2012. On admission, his corrected serum calcium level was 9.3 mg/dL, and his intact parathyroid hormone level was 121.9 pg/mL (normal range 13.9-78.5 pg/mL), indicating secondary hyperparathyroidism due to ESRD. After starting hemodialysis, urinary volume diminished rapidly. The serum calcium level increased (12.7 mg/dL), and the intact parathyroid hormone level was suppressed (< 5 pg/mL), while the 1,25-dihydroxyvitamin D3 (calcitriol) level increased (114 pg/mL, normal range: 20.0-60.0 pg/mL) in June 2012. The possibilities of sarcoidosis and tuberculosis were ruled out. Skin biopsies from tumorous lesions revealed a diagnosis of granulomatous mycosis fungoides. The serum soluble interleukin-2 receptor levels and the degrees of skin lesions went in parallel with the increased serum calcium and calcitriol levels. Therefore, the patient was diagnosed as having calcitriol-induced hypercalcemia possibly associated with granulomatous mycosis fungoides. Granulomatous mycosis fungoides is rare, and its association with calcitriol-induced hypercalcemia has not been reported. Careful attention to calcium metabolism is needed in patients with granulomatous mycosis fungoides, especially in patients with ESRD. PMID:24175265

  7. Interleukin 1 synthesis by a transitional cell carcinoma: relationship to bone resorption and humoral hypercalcemia of malignancy

    SciTech Connect

    Sammon, P.; Wronski, T.; Ignaszewski, L.; Flueck, J.; Cohen, D.A.

    1986-03-01

    A tumor cell line (TCCB) was isolated from a patient with transitional cell carcinoma, who had tumor-associated hypercalcemia. Culture supernatants from TCCB had significant bone resorption activity in a /sup 45/Ca release assay from fetal mouse long bones. Furthermore, TCCB supernatants possessed potent interleukin 1 (IL-1) activity in a mouse thymocyte assay. Histomorphometric analysis of fetal mouse long bones incubated with TCCB supernatants showed a 7 fold increase in osteoclasts and a significant decrease in bone mass as compared to control bones. IL-1 activity in culture supernatants from lipopolysaccharide-stimulated human monocytes comigrated with both IL-1 and bone resorption activities from TCCB tumor cells by gel chromatography on AcA-54 ultrogel. Furthermore, antisera against human IL-1 was shown to inhibit the Il-1 activity from both monocytes and TCCB tumor cells. In light of recent reports that IL-1 can cause bone resorption in vitro, these data suggest that the hypercalcemia of malignancy seen with certain solid tumors, may be the result of IL-1 release by the tumor which subsequently elevates serum calcium by induction of bone resorption.

  8. A Male Patient with Humoral Hypercalcemia of Malignancy (HHM) with Leukocytosis Caused by Cutaneous Squamous Cell Carcinoma Resulting from Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Miura, Kohji; Umegaki, Noriko; Kitaoka, Taichi; Kubota, Takuo; Namba, Noriyuki; Etani, Yuri; Hirai, Haruhiko; Kogaki, Shigetoyo; Nakajima, Shigeo; Takahashi, Yuji; Tamai, Katsuto; Katayama, Ichiro; Ozono, Keiichi

    2011-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disorder. Although the patients are at risk for cutaneous squamous cell carcinoma (SCC), no case of cutaneous SCC derived from RDEB with humoral hypercalcemia of malignancy (HHM) has been reported. We present the first case report of a male patient with HHM with leukocytosis caused by cutaneous SCC resulting from RDEB. A 20-yr-old Japanese male patient with RDEB; the diagnosis was confirmed by electron microscopic examination, suffered an intractable skin ulcer and hypercalcemia and leukocytosis. PTH-rP, SCC antigen and Granulocyte colony-stimulating factor (G-CSF) levels were elevated. The histological diagnosis of the skin lesion was made well-differentiated SCC. Immunohistochemical staining showed the expression of PTH-rP in atypical tumor cells. For the control of hypercalcemia before an amputation, we used zoledronate safely and could control the serum Ca concentration in the normal range. After the amputation of his right leg including SCC, leukocytosis improved immediately and PTH-rP in blood decreased to the normal range. One month after the amputation, local recurrence of cutaneous SCC and multiple lung metastases were observed. PTH-rP increased gradually associated with hypercalcemia. Although the patient reached an unfortunate turning point about 4 mo after the amputation, we propose that zoledronate is an effective and safe treatment for HHM with cardiorenal complications. PMID:23926398

  9. Hypercalcemia, hypervitaminosis A and 3-epi-25-OH-D3 levels after consumption of an "over the counter" vitamin D remedy. a case report.

    PubMed

    Granado-Lorencio, F; Rubio, E; Blanco-Navarro, I; Pérez-Sacristán, B; Rodríguez-Pena, R; García López, F J

    2012-06-01

    Intoxication from vitamin D supplements has been rarely reported but, nowadays, it occurs more frequently. 3-epi-25-OH-D(3) is highly prevalent in adults and it is considered of biological relevance. We report a case of vitamin D toxicity with hypercalcemia, acute renal failure and hypervitaminosis A after consuming an over-the-counter vitamin D supplement. Our data suggest that the contribution of 3-epi-25-OH-D(3) is not altered during vitamin D toxicity, although the serum levels of 25-OH-D(3) and 3-epi-25-OH-D(3) may display a different rate of clearance. The patient also displayed hypervitaminosis A unrelated to diet, possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity. Because of the increasing use of over-the-counter vitamin D supplements and the potential iatrogenic hypercalcemia related to hypervitaminosis A, the present case highlights the importance of evaluating both the use of (non-) prescribed medication and vitamin A status during vitamin D toxicity. PMID:22426357

  10. A Case of Hypercalcemia and Overexpression of CYP27B1 in Skeletal Muscle Lesions in a Patient with HIV Infection After Cosmetic Injections with Polymethylmethacrylate (PMMA) for Wasting.

    PubMed

    Hindi, Sahar M; Wang, Yongmei; Jones, Kirk D; Nussbaum, Jesse C; Chang, Yongen; Masharani, Umesh; Bikle, Daniel; Shoback, Dolores M; Hsiao, Edward C

    2015-12-01

    Foreign body-induced granuloma is an uncommon yet clinically significant cause of hypercalcemia. The molecular mechanisms are uncertain, although extrarenal calcitriol production has been proposed. We describe severe hypercalcemia associated with increased levels of plasma calcitriol in a patient with HIV and local granulomatous reaction 5 years after injection of polymethylmethacrylate (PMMA) as dermal filler for cosmetic body sculpting. Extensive evaluation revealed no identifiable cause of increased calcitriol levels. Nuclear imaging was remarkable for diffuse uptake in the subcutaneous tissues of the buttocks. Subsequent muscle biopsy and immunohistochemical staining showed strong local expression of CYP27B1 within histiocytes surrounding globules of PMMA. This case highlights an unfortunate complication of dermal fillers and shows that inflammatory cells can express high levels of CYP27B1 even without frank granulomas. The growing trend of body contour enhancement using injectable fillers should raise suspicion for this cause of hypercalcemia in clinical practice. Patients with HIV who receive this treatment for lipodystrophy or other cosmetic purposes may have increased susceptibility to hypercalcemia in the setting of underlying chronic inflammation. This may be a concern when changing anti-retroviral therapy, since alterations in levels of HIV viremia may initiate or contribute to worsening hypercalcemia. PMID:26253396

  11. Targeted 25-hydroxyvitamin D3 1α-hydroxylase adoptive gene therapy ameliorates dss-induced colitis without causing hypercalcemia in mice.

    PubMed

    Li, Bo; Baylink, David J; Walter, Michael H; Lau, Kin-Hing William; Meng, Xianmei; Wang, Jun; Cherkas, Andriy; Tang, Xiaolei; Qin, Xuezhong

    2015-02-01

    Systemic 1,25(OH)2D3 treatment ameliorating murine inflammatory bowel diseases (IBD) could not be applied to patients because of hypercalcemia. We tested the hypothesis that increasing 1,25(OH)2D3 synthesis locally by targeting delivery of the 1α-hydroxylase gene (CYP27B1) to the inflamed bowel would ameliorate IBD without causing hypercalcemia. Our targeting strategy is the use of CD11b(+)/Gr1(+) monocytes as the cell vehicle and a macrophage-specific promoter (Mac1) to control CYP27B1 expression. The CD11b(+)/Gr1(+) monocytes migrated initially to inflamed colon and some healthy tissues in dextran sulfate sodium (DSS) colitis mice; however, only the migration of monocytes to the inflamed colon was sustained. Adoptive transfer of Gr1(+) monocytes did not cause hepatic injury. Infusion of Mac1-CYP27B1-modified monocytes increased body weight gain, survival, and colon length, and expedited mucosal regeneration. Expression of pathogenic Th17 and Th1 cytokines (interleukin (IL)-17a and interferon (IFN)-α) was decreased, while expression of protective Th2 cytokines (IL-5 and IL-13) was increased, by the treatment. This therapy also enhanced tight junction gene expression in the colon. No hypercalcemia occurred following this therapy. In conclusion, we have for the first time obtained proof-of-principle evidence for a novel monocyte-based adoptive CYP27B1 gene therapy using a mouse IBD model. This strategy could be developed into a novel therapy for IBD and other autoimmune diseases. PMID:25327179

  12. Renal Failure Found during the Follow-up of Sarcoidosis: The Relevance of a Delay in the Diagnosis of Concurrent Hypercalcemia.

    PubMed

    Hishida, Erika; Masuda, Takahiro; Akimoto, Tetsu; Sato, Ryuta; Wakabayashi, Natsuko; Miki, Atsushi; Otani, Naoko; Imai, Toshimi; Sugase, Taro; Takeda, Shin-Ichi; Muto, Shigeaki; Nagata, Daisuke

    2016-01-01

    We herein present a case of relapsed sarcoidosis with a deteriorated renal function accompanied by hypercalcemia, nephrolithiasis, and a ureteral stone in a woman with a history of ocular sarcoidosis. The ocular involvement appeared to be well controlled for a long period of time with a topical ophthalmic steroid; however, we believe that the absence of apparent recrudescence could have led to the delay in our diagnosis of relapse of the disease during the follow-up period. The conundrums regarding longitudinal surveillance for both evaluating the disease activity and determining the necessity of therapeutics are also discussed. PMID:27432099

  13. 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

  14. A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2).

    PubMed

    Gorvin, Caroline M; Cranston, Treena; Hannan, Fadil M; Rust, Nigel; Qureshi, Asjid; Nesbit, M Andrew; Thakker, Rajesh V

    2016-06-01

    Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous disorder with three variants, FHH1 to FHH3. FHH1 is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), a G-protein coupled receptor that predominantly signals via G-protein subunit alpha-11 (Gα11 ) to regulate calcium homeostasis. FHH2 is the result of loss-of-function mutations in Gα11 , encoded by GNA11, and to date only two FHH2-associated Gα11 missense mutations (Leu135Gln and Ile200del) have been reported. FHH3 is the result of loss-of-function mutations of the adaptor protein-2 σ-subunit (AP2σ), which plays a pivotal role in clathrin-mediated endocytosis. We describe a 65-year-old woman who had hypercalcemia with normal circulating parathyroid hormone concentrations and hypocalciuria, features consistent with FHH, but she did not have CaSR and AP2σ mutations. Mutational analysis of the GNA11 gene was therefore undertaken, using leucocyte DNA, and this identified a novel heterozygous GNA11 mutation (c.161C>T; p.Thr54Met). The effect of the Gα11 variant was assessed by homology modeling of the related Gαq protein and by measuring the CaSR-mediated intracellular calcium (Ca(2+) i ) responses of HEK293 cells, stably expressing CaSR, to alterations in extracellular calcium (Ca(2+) o ) using flow cytometry. Three-dimensional modeling revealed the Thr54Met mutation to be located at the interface between the Gα11 helical and GTPase domains, and to likely impair GDP binding and interdomain interactions. Expression of wild-type and the mutant Gα11 in HEK293 cells stably expressing CaSR demonstrate that the Ca(2+) i responses after stimulation with Ca(2+) o of the mutant Met54 Gα11 led to a rightward shift of the concentration-response curve with a significantly (p < 0.01) increased mean half-maximal concentration (EC50 ) value of 3.88 mM (95% confidence interval [CI] 3.76-4.01 mM), when compared with the wild-type EC50 of 2.94 mM (95% CI 2.81-3.07

  15. Sarcoidosis presenting with an unusual erythematous rash and persistent hypercalcemia.

    PubMed Central

    Barney, B. L.

    1992-01-01

    Sarcoidosis is a multisystem disease that often presents with constitutional symptoms and ocular and skin manifestations. The chest roentgenogram may show no abnormalities or only diffuse interstitial disease. The serum calcium level is uncommonly persistently elevated and responds rapidly to low-dose corticosteroid therapy. The level of 1,25-dihydroxyvitamin D is often elevated, and the level of parathyroid hormone is almost always suppressed. Skin manifestations vary considerably and may appear in an unusual fashion. A skin biopsy may often be essential in the diagnosis of sarcoidosis. Images PMID:1595285

  16. Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.

    PubMed

    Azuma, Y; Sato, H; Oue, Y; Okabe, K; Ohta, T; Tsuchimoto, M; Kiyoki, M

    1995-02-01

    Alendronate is an aminobisphosphonate that acts as a potent inhibitor of osteoclastic bone resorption. To understand the mechanism of action of alendronate in vivo, in this study we investigated the relationship between distribution of [14C]-alendronate in rat bone and its effects on bone resorption in vitro or in rat hypercalcemic models. A single IV dose of 0.05 approximately 1.25 mg/kg inhibited the increase in plasma calcium level induced by bovine PTH or 1 alpha(OH)D3. The minimal effective dose of pamidronate (1.25 mg/kg) and etidronate (over 31.25 mg/kg) were at least 5 times and 25 times, respectively, higher than the dose of alendronate in the rat hypercalcemic model prepared by 1 alpha(OH)D3. The relative potencies of compounds in the hypercalcemic rat models reflected those of inhibitory effects on bone resorption in vitro. We conducted the ivory-slice assay under two conditions: (a) addition of a given bisphosphonate after adherence of the osteoclasts; and (b) preincubation of the ivory slices with a given bisphosphonate. The inhibitory IC50 values of alendronate under condition (b) were similar to those under condition (a). To evaluate the interaction between osteoclasts and alendronate in bone, we investigated the localization of [14C]-alendronate in the tibia of growing rats (4-day-old rats). Alendronate did not distribute uniformly in the tibia. At 1 day after injection (0.05 mg SC), dense labeling was seen primarily under osteoclasts. We injected 0.05 mg/kg of [14C]-alendronate (single i.v.) into rats [14C]-alendronate was rapidly eliminated from plasma, and mainly distributed to the bone in rats. These data suggest that alendronate which distributed on bone surface mainly contributed to the antihypercalcemic action in vivo. PMID:7756053

  17. Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations.

    PubMed

    2016-06-01

    In the full list of authors as shown in the PDF file posted with the published letter at NEJM.org, Drs. Nesbit and Thakker should have been listed as the penultimate and final authors, rather than as the seventh and eighth authors. The letter is correct at NEJM.org. PMID:27276582

  18. 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

  19. [Influence of an acute hypercalcemia on the gastric secretion in duodenal ulcer, peptic ulcer of the jejunum and Zollinger-Ellison syndrome].

    PubMed

    Arendt, R

    1975-05-15

    In 36 patients with ulcer without Zollinger-Ellison-syndrome (25 patients with recurrent duodenal ulcer, 11 with an ulcus pepticum jejuni after B II-resection of the stomach) and 2 patients suffering from ulcus pepticum jejuni with an ascertained gastrinoma the secretion of acid was compared after stimulation of pentagstrin (6 mug/kg) and calcium (4 mg Ca++/kg/h). The secretion of hydrochloric acid was statistically significantly stimulated in all patients suffering from ulcer by the hypercalcaemia (increase of the serum calcium concentration from 5.0 +/- 0.3 mval/1 to 6.2 +/- 0.8 mval/1). But in patients suffering from ulcer with gastrinoma the stimulatory effect was larger than in such patients without autonomous source of gastrin: the calcium-stimulated secretion of hydrochloric acid was on the average in cases of duodenal ulcer 40% (2 to 68%), in the ulcera peptica jejuni 47% (17 to 75%), in the 4 comparative examinations of the two patients with Zollinger-Ellison-syndrome, however, always more than 100% (106 to 177%) of the pentagastrin-stimulated peak secretion. The comparative test of the pentagastrin and calcium-stimulated secretion of hydrochloric acid could be a help for the proof of autonomous places of the formation of gastrin. PMID:1199239

  20. Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome.

    PubMed

    Mancano, Michael A

    2015-10-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:26912914

  1. A Case of Solitary Kidney Atrophy Due to Primary Hyperparathyroidism

    PubMed Central

    Lin, Yu-Ting; Jiang, Jiunn-Song; Fang, Yu-Wei; Tsai, Ming-Hsien

    2016-01-01

    Abstract Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time. We present a rare case of a large unilateral asymptomatic ureteral stone in a patient with hypercalcemia secondary to PHPT, which eventually led to renal atrophy. The diagnosis of PHPT should be considered in patients with hypercalcemia and renal stones, as asymptomatic PHPT may result in a devastating renal outcome. PMID:26765435

  2. PubMed Central

    Bergeron, R.; Martin, N.; Moreau, A.

    1995-01-01

    The most frequent, potentially fatal, metabolic complication in cancer patients is hypercalcemia. After a discussion of cancer-associated hypercalcemia, we propose an individualized intervention model based on an analysis of the clinical situation, the prognosis, and available treatment options. PMID:7773028

  3. A case of adolescent giant parathyroid adenoma presenting multiple osteolytic fractures and postoperative hungry bone syndrome

    PubMed Central

    Ebina, Kosuke; Miyoshi, Yuji; Izumi, Shinji; Hashimoto, Jun; Naka, Norifumi; Tsukamoto, Yasunori; Kashii, Masafumi; Kaito, Takashi; Yoshikawa, Hideki

    2015-01-01

    Key Clinical Message Primary hyperparathyroidism (PHPT) and postoperative hungry bone syndrome are very rare conditions in adolescents, and may be frequently misdiagnosed as a metastatic bone tumor. However, delay in diagnosis may lead to a fatal preoperative hypercalcemia and postoperative hypocalcemia. PHPT is a differential diagnosis of adolescent hypercalcemia and osteolytic fractures. PMID:26509019

  4. [Renal ultrasound in fat necrosis].

    PubMed

    Tizki, S; Lasry, F; Elftoiki, F Z; Hadj Khalifa, H; Itri, M; Khadir, K; Benchikhi, H

    2013-07-01

    Subcutaneous fat necrosis is an uncommon disease that may be complicated with potentially fatal hypercalcemia or with nephrocalcinosis. We report on the case of a patient with a history of significant perinatal asphyxia, hospitalized for a urinary tract infection. Lesions of subcutaneous fat necrosis were noted, with asymptomatic hypercalcemia at 3.9mmol/L. A renal ultrasound was performed and showed echogenic medullary pyramids bilaterally, consistent with nephrocalcinosis and left nephrolithiasis. The treatment of hypercalcemia included hyperhydration, a diuretic and corticosteroids. Progression was characterized by the total regression of skin lesions and normalization of serum calcium. Hypercalcemia is a rare complication of subcutaneous fat necrosis. It develops within days to weeks after the appearance of skin lesions. Nephrocalcinosis appears after several weeks or months. Hypercalcemia must be treated in due time to avoid the impact on the kidney. PMID:23726682

  5. Endocrine causes of calcium disorders.

    PubMed

    Greco, Deborah S

    2012-11-01

    Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients. PMID:23415381

  6. IN VITRO INHIBITORY AND FUNGICIDAL PROPERTIES OF EDTA FOR ASPERGILLUS AND FUSARIUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Ethylenediaminetetra-acetic acid (EDTA) is approved for food preservation, treatment for hypercalcemia and heavy metal poisoning and as a blood count tube anticoagulant. Reports indicate EDTA also inhibits microbial growth. This study investigated EDTA lethality and inhibitory propert...

  7. Primary hyperparathyroidism in children and adolescents

    PubMed Central

    Roizen, Jeffrey; Levine, Michael A.

    2013-01-01

    Primary hyperparathyroidism (PHPT) is a common endocrine disorder in adults in whom the typical presentation is incidentally discovered as asymptomatic hypercalcemia. PHPT is much less common in children and adolescents, but has greater morbidity in this age group, as most young patients with PHPT will have symptomatic hypercalcemia or complications such as kidney stones, abdominal pain, and skeletal fragility. An important feature of PHPT in younger patients is the relatively high prevalence of germline inactivating mutations of the CASR gene, which encodes the calcium-sensing receptor. Biallelic CASR mutations cause neonatal severe hyperparathyroidism, a life-threatening condition that presents within days of life with marked hypercalcemia, respiratory distress, failure to thrive, and skeletal demineralization. By contrast, more common heterozygous CASR mutations are generally associated with a benign variant of PHPT termed familial hypocalciuric hypercalcemia. Appropriate management of PHPT in children and adolescents requires distinction between familial hypocalciuric hypercalcemia, which generally requires no specific treatment, and other forms of PHPT that are best treated by parathyroidectomy. PMID:22989537

  8. 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

  9. Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.

    PubMed

    Figueres, Marie-Lucile; Linglart, Agnès; Bienaime, Frank; Allain-Launay, Emma; Roussey-Kessler, Gwenaelle; Ryckewaert, Amélie; Kottler, Marie-Laure; Hourmant, Maryvonne

    2015-01-01

    Loss-of-function mutations of CYP24A1, the enzyme that converts the major circulating and active forms of vitamin D to inactive metabolites, recently have been implicated in idiopathic infantile hypercalcemia. Patients with biallelic mutations in CYP24A1 present with severe hypercalcemia and nephrocalcinosis in infancy or hypercalciuria, kidney stones, and nephrocalcinosis in adulthood. We describe a cohort of 7 patients (2 adults, 5 children) presenting with severe hypercalcemia who had homozygous or compound heterozygous mutations in CYP24A1. Acute episodes of hypercalcemia in infancy were the first symptom in 6 of 7 patients; in all patients, symptoms included nephrocalcinosis, hypercalciuria, low parathyroid hormone (PTH) levels, and higher than expected 1,25-dihydroxyvitamin D levels. Longitudinal data suggested that in most patients, periods of increased sunlight exposure tended to correlate with decreases in PTH levels and increases in calcemia and calciuria. Follow-up of the 2 adult patients showed reduced glomerular filtration rate and extrarenal manifestations, including calcic corneal deposits and osteoporosis. Cases of severe PTH-independent hypercalcemia associated with hypercalciuria in infants should prompt genetic analysis of CYP24A1. These patients should be monitored carefully throughout life because they may be at increased risk for developing chronic kidney disease. PMID:25446019

  10. 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

  11. Creutzfeldt-Jakob-Like Syndrome due to Hypercalcemic Encephalopathy.

    PubMed

    Rösche, Johannes; Sieveking, Catharina; Kampf, Christina; Benecke, Reiner

    2015-10-01

    Hypercalcemia can cause a subacute syndrome of progressive dementia and marked changes in the electroencephalogram (EEG). We report a case of iatrogenic hypercalcemia with a close correlation between the clinical course and the EEG changes. A 73-year-old woman presented with a subacute syndrome of progressive dementia and bursts of 1.5 to 2 Hz intermittent rhythmic delta activity superimposed on a low-voltage background activity in the EEG. Clinical and EEG abnormalities rapidly resolved after normalization of serum calcium levels. As part of the diagnostic workup of a subacute progressive dementia, a serum calcium level and an EEG should be obtained to detect a Creutzfeldt-Jakob like syndrome in hypercalcemia. Unlike in Creutzfeldt-Jakob disease, and Creutzfeldt-Jakob-like syndrome induced by lithium intoxication, there are rarely myoclonic jerks and periodic discharges in hypercalcemic encephalopathy. PMID:24973231

  12. Renal tubular acidosis due to the milk-alkali syndrome.

    PubMed

    Rochman, J; Better, O S; Winaver, J; Chaimowitz, C; Barzilai, A; Jacobs, R

    1977-06-01

    A 60-year-old man with a history of excessive ingestion of calcium carbonate presented with azotemia, hypercalcemia and hyperphosphatemia. His acid-base status was initially normal. Following the cessation of calcium carbonate treatment, the hypercalcemia and azotemia disappeared, and the patient was found to be in metabolic acidosis with blunted acid excretion and a urine pH of 6.1. Kidney biopsy showed focal tubular calcification; the tubular damage was apparently caused by hypercalcemia and had resulted in renal tubular acidosis. During the three months of observation since that time there has been a tendecy for spontaneous remission of the renal tubular acidosis. Impaired renal hydrogen ion excretion prevented the development of metabolic alkalosis despite ingestion of alkali initially, and was later responsible for the metabolic acidosis. Renal tubular acidosis occurring as a sequel to the milk-alkali syndrome may aggravate the danger of nephrocalcinosis in this syndrome. PMID:885714

  13. Primary hyperparathyroidism with duodenal ulcer and H. pylori infection.

    PubMed

    Sato, Hiroshi; Abe, Keiko; Oshima, Naoki; Kawashima, Kousaku; Hamamoto, Naoharu; Moritani, Makoto; Mak, Rumi; Ishihara, Shunji; Adachi, Kyoichi; Kawauchi, Hideyuki; Kinoshita, Yoshikazu

    2002-05-01

    A patient with duodenal ulcer and primary hyperparathyroidism was found to have an abnormally high intragastric pH. The pH level returned to normal after surgical removal of the parathyroid adenoma followed by normalization of parathyroid hormone (PTH) and serum calcium concentrations. The patient was positive for Helicobacter pylon (H. pylori) infection. Although the exact mechanism by which chronic hypercalcemia or high PTH level inhibited gastric acid secretion in this case remains unclear, our findings suggest that hypercalcemia may play some role in H. pylori associated gastroduodenal diseases through induction of proinflammatory cytokines or by enhancing the attachment of H. pylori to gastric epithelial cells. PMID:12058887

  14. Squamous Cell Carcinoma of the Renal Pelvis as a Result of Long-Standing Staghorn Calculi

    PubMed Central

    Jongyotha, Kamonchanok; Sriphrapradang, Chutintorn

    2015-01-01

    We report on a 79-year-old woman with staghorn calculi who presented with severe hypercalcemia. She was later found to have humoral hypercalcemia of malignancy caused by a rare tumor, squamous cell carcinoma of the renal pelvis. Chronic irritation, infection and inflammation from staghorn stones cause squamous metaplasia, leading to squamous cell carcinoma of the renal collecting system. The prognosis is very poor, with a 5-year survival rate of <10%. This case highlights the importance of awareness of a very rare and aggressive carcinoma in a patient with long-standing nephrolithiasis. PMID:26557077

  15. The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

    PubMed Central

    Lee, David B. N.; Zawada, Edward T.; Kleeman, Charles R.

    1978-01-01

    For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism. PMID:362722

  16. Four Case Histories and a Literature Review of Williams Syndrome and Autistic Behavior.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; Rasmussen, Peder

    1994-01-01

    This paper summarizes the case histories of four young children with concurrent autistic disorder and Williams syndrome. Williams syndrome comprises a peculiar facial appearance, learning disorder, and often hypercalcemia, mild microcephaly, large blood vessel stenosis, and a specific behavioral phenotype. Literature on Williams syndrome is…

  17. Primary hyperparathyroidism: an uncommon cause of hip pain.

    PubMed

    Waseem, Muhammad; Erickson, Evelyn; Agyare, Samuel; Godil, Mushtaq A

    2015-04-01

    Hip pain is a common complaint in a pediatric emergency department. The causes of hip pain are diverse and generally include traumatic and infectious causes. We report a case of hip pain caused by deep soft tissue infection associated with hypercalcemia and primary hyperparathyroidism. Atypical presentation of primary hyperparathyroidism may result in a delay in diagnosis. PMID:25831028

  18. Emergency medicine: A comprehensive review

    SciTech Connect

    Kravis, T.C.; Warner, C.G.

    1987-01-01

    This book contains 91 chapters divided among 14 sections. Some of the chapter titles are: Transfusions; Minor Lacerations and Abrasions; Diabetic Emergencies; Adrenal Insufficiency; Hypercalcemia; Medical Genetics; Burns; Hazardous Materials; Gastrointestinal Emergencies; Infectious Disease Emergencies; Reye's Syndrome; Bites and Stings; and Hypothermia.

  19. 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

  20. 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

  1. No more milk in milk-alkali syndrome: a case report.

    PubMed

    Almusawi, Ali; Alhawaj, Shurooq; Al-Mousawi, Mohammed; Dashti, Tareq

    2012-09-01

    This is a case of Milk-AlKali syndrome in a patient who presented with the classical triad of hypercalcemia, metabolic alkalosis and renal impairment. The source of calcium was over-the-counter calcium-containing antacid (Tums®). Milk-alkali syndrome was first recognized secondary to treatment of peptic ulcer disease with milk and absorbable alkali. Its incidence fell after the introduction of H2-blocker and proton pump inhibitor. However, it is one of the leading causes of hypercalcemia nowadays because of the wide availability, increased marketing and use of calcium carbonate especially in osteoporosis prevention and treatment. The demographics of milk-alkali syndrome have changed compared to when it was initially described. The presentation could be acute, subacute or chronic. Early diagnosis, discounting calcium supplement and intravenous hydration are the mainstay of MAS management. PMID:23074554

  2. A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors, Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1

    PubMed Central

    Yamamoto, Yoko; Kodama, Ken; Yokoyama, Shigekazu; Takeda, Masashi; Michishita, Shintaro

    2015-01-01

    Neurofibromatosis type 1 (NF1), also called von Recklinghausen's disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2). Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed. PMID:26442164

  3. Turner syndrome with primary hyperparathyroidism

    PubMed Central

    Park, Jungmee; Kim, Yoo-Mi; Choi, Jin-Ho; Lee, Beom Hee; Yoon, Jong Ho; Jeong, Woon-Young

    2013-01-01

    Turner syndrome has multiple comorbidities such as osteoporosis, obesity, diabetes, hypothyroidism, and hypertension. As they are treatable conditions in Turner syndrome, early recognition and proper treatment should be needed. We report on a 23-year-old woman with Turner syndrome who presented with severe osteoporosis and hypercalcemia. Laboratory tests showed elevated levels of serum calcium and parathyroid hormone. Dual-energy X-ray absorptiometry showed severe osteopo-rosis (z score, -3.5). Ultrasound and 99mTc scintigraphy of parathyroid glands showed an adenoma in the right inferior gland. She was diagnosed with primary hyperparathyroidism due to an adenoma of the parathyroid gland. After excision of the adenoma, the patient's serum calcium and parathyroid hormone levels returned to normal. Although only a few cases of Turners syndrome with primary hyperparathyroidism have been reported, hyperparathyroidism should be considered in cases of Turner syndrome with severe osteoporosis and hypercalcemia. PMID:24904858

  4. Radioiodine-induced thyroid storm. Case report and literature review

    SciTech Connect

    McDermott, M.T.; Kidd, G.S.; Dodson, L.E. Jr.; Hofeldt, F.D.

    1983-08-01

    Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

  5. Calcium kinetics in the Solanum malacoxylon-treated rat.

    PubMed

    Cabrejas, M; Ladizesky, M; Mautalen, C A

    1975-12-01

    The chronic ingestion of the leaves of the plant Solanum malacoxylon (SM) causes an endemic disease in the cattle of some areas of Buenos Aires province. The animals affected manifest loss of appetite and weight, hypercalcemia, hyperphosphatemia, and ectopic calcifications. In order to study the mechanism of the hypercalcemia provoked by the administration of SM, a calcium kinetic study was performed in control and treated adult intact rats. The animals receiving SM showed higher levels of serum calcium throughout the study. The body excretion of 47Ca and the size of the most rapidly exchangeable calcium pool were also elevated. On the other hand, the bone accretion rate and the urinary excretion of total hydroxyproline were significantly diminished. The results indicate that during the early phase of SM administration in intact rats, bone turnover rate is depressed. PMID:1195017

  6. Diagnosis and treatment of primary hyperparathyroidism in a bobcat (Lynx rufus).

    PubMed

    Goodnight, Andrea L; Gottfried, Sharon D; Emanuelson, Karen

    2011-09-01

    An 18-yr-old male bobcat (Lynx rufus) presented with chronic moderate weight loss and acute onset of anorexia and lethargy. Hypercalcemia and azotemia were present on the serum chemistry panel. Abdominal ultrasound revealed hyperechoic renal cortices, but no evidence of neoplasia. Ionized calcium and 25-hydroxyvitamin D were mildly elevated, intact parathyroid hormone was severely elevated, and parathormone-related protein was undetected, suggesting primary hyperparathyroidism with possible renal dysfunction. Azotemia lessened in severity following diuresis, but hypercalcemia persisted; thus primary hyperparathyroidism was considered the most probable differential diagnosis. A second ultrasound including the cervical region revealed a solitary intraparenchymal left thyroid nodule. The nodule was surgically excised; histopathology confirmed a parathyroid adenoma. Although primary hyperparathyroidism was suspected, diagnosis was not achieved from serum chemistry values alone. This case emphasizes the importance of diagnostic imaging and histopathology in the investigation of persistently abnormal laboratory values. PMID:22950324

  7. [Nonsurgical management of mild primary hyperparathyroidism].

    PubMed

    Imanishi, Yasuo

    2016-06-01

    Primary hyperparathyroidism(PHPT)is one of the common endocrine disorders, which results clinically in nephrolithiasis, osteoporosis, muscle weakness, cardiac and psychiatric abnormalities even in a mild or asymptomatic disease. Parathyroidectomy(PTX)is the only definitive treatment for PHPT, however, some patients with sporadic PHPT refuse surgery, are medically unfit, or have residual or recurrent disease inaccessible to further surgery. These patients may require intervention for management of symptomatic or moderate to severe hypercalcemia, bone loss or kidney calculi. PMID:27230840

  8. Vitamin D intoxication.

    PubMed

    Ozkan, Behzat; Hatun, Sükrü; Bereket, Abdullah

    2012-01-01

    Vitamin D intoxication (VDI) may result from supplementation rarely, but it has been reported more frequently in recent years. This may be attributable to an increase in vitamin D supplement intake due to an understanding of the role of vitamin D (25OHD) in the pathogenesis of several diseases. The symptoms and findings associated with VDI are closely related to serum calcium concentration and duration of hypercalcemia. In patients with VDI, hypercalcemia, normal or high serum phosphorus levels, normal or low levels of alkaline phosphatase (ALP), high levels of serum 25OHD, low serum parathyroid hormone (PTH), and high urine calcium/creatinine are usually present. Serum 25OHD levels above 150 ng/ml are considered as VDI. The main goal of treatment for VDI is correction of the hypercalcemia. When the calcium concentration exceeds 14 mg/dl, emergency intervention is necessary because of the adverse effects of hypercalcemia on cardiac, central nervous system, renal, and gastrointestinal functions. However, since vitamin D is stored in fat tissues, effects of toxicity may last for months despite the removal of the exogenous source of vitamin D. Treatment for VDI includes: discontinuation of intake, a diet with low calcium and phosphorus content, intravenous hydration with saline, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates. In conclusion, the diagnosis of vitamin D deficiency rickets (VDDR) without checking serum 25OHD level may cause redundant treatment that leads to VDI. All patients who are clinically suspected of VDDR should be checked for serum vitamin D status and questioned for previous vitamin D administration before starting vitamin D therapy. On the other hand, parents of all infants should be asked whether they are using dietary or oral supplements, and serial questioning may be required during supplementation to avoid excessive intake. PMID:22734293

  9. Neonatal Seizure as a Manifestation of Unrecognized Maternal Hyperparathyroidism

    PubMed Central

    Korkmaz, Hüseyin Anıl; Özkan, Behzat; Terek, Demet; Dizdarer, Ceyhun; Arslanoğlu, Sertaç

    2013-01-01

    Maternal hypercalcemia suppresses parathyroid activity in the fetus resulting in impaired parathyroid responsiveness to hypocalcemia after birth. Resultant hypocalcemia may be severe and prolonged and rarely may lead to convulsions. Here, we present a newborn infant admitted to the pediatric emergency department at age two weeks with recurrent tonic convulsions due to asymptomatic maternal hyperparathyroidism and vitamin D deficiency. Physicians should be aware that undiagnosed maternal hyperparathyroidism can cause severe hypocalcemia in the newborn. Conflict of interest:None declared. PMID:24072092

  10. Emergencies in Oncology

    PubMed Central

    Stolinsky, David C.

    1978-01-01

    Malignant neoplasms may cause life-threatening complications requiring prompt diagnosis and emergency therapy. Whether or not the underlying neoplasm is potentially curable, the physician can often provide worthwhile prolongation of life and dramatic symptomatic relief. Among the serious complications of neoplasia are superior vena cava obstruction, airway obstruction, pericardial tamponade, spinal cord compression, brain metastasis, meningeal involvement by cancer, hyperuricemia, hypercalcemia and hyperkalemia. PMID:360621

  11. New aspects of treatment of renal bone disease in dialysis patients.

    PubMed

    Spasovski, G

    2007-07-01

    The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients. PMID:17932468

  12. Sevelamer as a phosphate binder in adult hemodialysis patients: an evidence-based review of its therapeutic value

    PubMed Central

    Nadin, Carole

    2005-01-01

    Introduction: Patients on hemodialysis require phosphate binders to reduce dietary phosphate absorption and control serum phosphate. The standard therapy, calcium salts, can be associated with elevated serum calcium (hypercalcemia). Concern has been raised that hypercalcemia, especially combined with elevated serum phosphate, may be associated with arterial calcification, and this may contribute to increased risk of cardiovascular mortality and morbidity. Sevelamer is a nonmetal, nonabsorbed phosphate binder. Aims: This review assesses the evidence for the therapeutic value of sevelamer as a phosphate binder in adult hemodialysis patients. Evidence review: Strong evidence shows that sevelamer is as effective as calcium salts in controlling serum phosphate and calcium–phosphate product, has less risk of inducing hypercalcemia and is more effective at lowering lipid levels. Some evidence indicates that sevelamer reduces arterial calcification progression and loss of bone mineral density, but it may be more likely to induce metabolic acidosis, compared with calcium salts. Sevelamer-containing regimens may improve calcific uremic arteriolopathy, although the evidence is weak. Evidence is divided on whether the incidence of gastrointestinal adverse events with sevelamer is similar to or higher than that with calcium salts. Retrospective and modeling studies suggest lower cardiovascular morbidity and mortality with sevelamer than with calcium salts, with incremental cost-effectiveness of $US1100–2200 per life-year gained. Further direct evidence is needed on mortality, quality of life, and cost-effectiveness. Place in therapy: Sevelamer is effective in controlling serum phosphate and lowering lipid levels in hemodialysis patients without inducing hypercalcemia, and may have beneficial effects on arterial calcification. PMID:22496676

  13. Unusual cases of chronic intoxication by vitamin D.

    PubMed

    Chiricone, Daniela; De Santo, Natale G; Cirillo, Massimo

    2003-01-01

    A 62-year-old man was hospitalized for recent renal colic and neurologic disorders. Routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 15.3 mg/100 mL) and renal failure (serum creatinine = 3.72 mg/100 mL). The patient reported that he had been on treatment with a slow-release multivitamin preparation containing vitamin D and vitamin A, administered by i.m. injection. Plasma 25-OH vitamin D was > 150 ng/mL (normal range 16-74 ng/mL), plasma 1,25-(OH)2 vitamin D was 32.5 pg/mL (normal range 14-60 pg/mL), plasma parathyroid hormone 1.3 pg/mL (normal range 10-65 pg/mL). There were calcifications of left and right iliac artery at abdomen x-ray. Ultrasound and computed tomography of the glutei showed alterations of skeletal muscle and calcifications. Immediate treatment with infusion of isotonic saline, furosemide and prednisone induced rapid control of hypercalcemia and renal failure. Chronic treatment per os was discontinued after six months. The patient reported that the treatment with vitamin D had been prescribed by a physician also to his wife (55-year-old). For the woman, routine biochemistry indicated the presence of hypercalcemia (serum total calcium = 11.3 mg/100 mL) and renal failure (serum creatinine = 1.8 mg/ mL). Plasma 25-OH vitamin D was > 150 ng/mL, plasma 1,25-(OH)2 vitamin D 47.9 pg/mL, plasma parathyroid hormone was 2.5 pg/mL. Hypercalcemia was acutely treated by oral hydration, furosemide, and prednisone. Chronic treatment per os was discontinued after five months. PMID:14736022

  14. 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.

  15. Persistent Primary Hyperparathyroidism, Severe Vitamin D Deficiency, and Multiple Pathological Fractures

    PubMed Central

    Carvallo-Venegas, Mauricio; Vargas-Castilla, Jorge Alberto; Balcázar-Hernández, Lourdes Josefina; Gregor-Gooch, Julián Malcolm Mac

    2016-01-01

    Persistent primary hyperparathyroidism (PHPT) refers to the sustained hypercalcemia state detected within the first six months following parathyroidectomy. When it coexists with severe vitamin D deficiency, the effects on bone can be devastating. We report the case of a 56-year-old woman who was sent to this center because of persistent hyperparathyroidism. Her disease had over 3 years of evolution with nephrolithiasis and hip fracture. Parathyroidectomy was performed in her local unit; however, she continued with hypercalcemia, bone pain, and pathological fractures. On admission, the patient was bedridden with multiple deformations by fractures in thoracic and pelvic members. Blood pressure was 100/80, heart rate was 86 per minute, and body mass index was 19 kg/m2. Calcium was 14 mg/dL, parathormone 1648 pg/mL, phosphorus 2.3 mg/dL, creatinine 2.4 mg/dL, urea 59 mg/dL, alkaline phosphatase 1580 U/L, and vitamin D 4 ng/mL. She received parenteral treatment of hypercalcemia and replenishment of vitamin D. The second surgical exploration was radioguided by gamma probe. A retroesophageal adenoma of 4 cm was resected. Conclusion. Persistent hyperparathyroidism with severe vitamin D deficiency can cause catastrophic skeletal bone softening and fractures. PMID:27525132

  16. Acute Vitamin D Intoxication Possibly Due to Faulty Production of a Multivitamin Preparation

    PubMed Central

    Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Dizdarer, Ceyhun; Böber, Ece

    2013-01-01

    Vitamin D intoxication usually occurs as a result of inappropriate use of vitamin D preparations and can lead to life-threatening hypercalcemia. It is also known that there are a number of physicians who prescribe vitamin D supplements for various clinical conditions, such as poor appetite and failure to thrive. While inappropriate use of vitamin D supplements may lead to vitamin D intoxication, there are no reports of cases of vitamin D toxicity due to manufacturing errors of vitamin D preparations. Here, we present cases of hypervitaminosis D which developed following the use of a standard dose of a multivitamin preparation. All three cases presented with hypercalcemia symptoms and had characteristic laboratory findings such as hypercalcemia, hypercalciuria, low levels of parathyroid hormone. The very high serum 25(OH) vitamin D levels in these patients indicated vitamin D excess. The vitamin D level of the prescribed multivitamin preparation in the market was studied and was found to contain a very low level of vitamin D (10 IU/5 mL). Although the stated vitamin D content of the preparations ingested by these patients was not high, unproven but possible manufacturing errors were considered to be a possible cause of the hypervitaminosis D diagnosed in these three patients. Conflict of interest:None declared. PMID:23748070

  17. The calcium-alkali syndrome.

    PubMed

    Arroyo, Mariangeli; Fenves, Andrew Z; Emmett, Michael

    2013-04-01

    The milk-alkali syndrome was a common cause of hypercalcemia, metabolic alkalosis, and renal failure in the early 20th century. It was caused by the ingestion of large quantities of milk and absorbable alkali to treat peptic ulcer disease. The syndrome virtually vanished after introduction of histamine-2 blockers and proton pump inhibitors. More recently, a similar condition called the calcium-alkali syndrome has emerged as a common cause of hypercalcemia and alkalosis. It is usually caused by the ingestion of large amounts of calcium carbonate salts to prevent or treat osteoporosis and dyspepsia. We describe a 78-year-old woman who presented with weakness, malaise, and confusion. She was found to have hypercalcemia, acute renal failure, and metabolic alkalosis. Upon further questioning, she reported use of large amounts of calcium carbonate tablets to treat recent heartburn symptoms. Calcium supplements were discontinued, and she was treated with intravenous normal saline. After 5 days, the calcium and bicarbonate levels normalized and renal function returned to baseline. In this article, we review the pathogenesis of the calcium-alkali syndrome as well as the differences between the traditional and modern syndromes. PMID:23543983

  18. 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

  19. Reoperation for primary hyperparathyroidism.

    PubMed Central

    McGarity, W C; Goldman, A L

    1981-01-01

    Between 1960 and April, 1980, 302 patients were explored for primary hyperparathyroidism at Emory University Hospital. Seventeen of these 302 patients had undergone initial surgical exploration elsewhere, and were referred for persistent hypercalcemia. Of the 285 patients who were operated on at our institution, 14 subsequently had persistent hypercalcemia, and two had recurrent hypercalcemia. Twenty-eight of these 33 patients had had re-exploration, and 23 (82%) are now normocalcemic. Twenty-eight abnormal glands were found; 22 (79%) were retrievable via the neck and six (21%) required sternotomy. Of those glands removed via the neck, nine were in a near normal location and 13 in a subnormal or abnormal location. The causes of initial surgical failures were abnormally located glands, in ten patients, insufficient explorations of the neck in eight patients, hyperfunctioning parathyroid remnants in three patients, inadequate plans for hyperplasia in two patients, and carcinoma in one patient. In 57% of our patients who underwent successful re-exploration, the glands were correctly localized before operation by angiographic examination or selective venous sampling for parathormone. Thorough exploration and obtainment of biopsy specimens of all parathyroid glands are recommended in order to keep initial failures to a minimum. If reoperation is required, localization using CT scan, angiography and selective venous sampling are recommended. PMID:7259338

  20. [Postoperative hypoparathyroidism: risk of complications].

    PubMed

    Sawicki, A

    For assessing the risk of adverse complications of surgery the group of 130 patients with post-operational hypoparathyroidism was analysed. Surgical hypoparathyroidism has been diagnosed in 51% of operated on thyroid gland patients. Laryngeal nerves have been damaged in 46.6% of patients. The injury to laryngeal nerves has been irreversible in 2/3 of patients, and reversible in the remaining 1/3. Cataract, nephrolithiasis and vitamin D3 intoxication have been observed in some cases before surgery. Their incidence increased in severe surgical hypoparathyroidism. Osteoporosis of the spine has been diagnosed in 49% of patients including some with vertebral fractures. No correlation between the degree of spine osteoporosis and diagnosis before surgery, number of operations on thyroid gland, and type of therapy has been noted. The symptoms of hypercalcemia have been diagnosed in 5 patients out of which hypercalcemia has been transient in 2 patients, and lasted for 1-5 months in the remaining 3 patients. The results of 7,873 analyses of mineral metabolism have been assessed. Hypocalcemia has been found in 38.4%, hypercalcemia in 1.6%, hypomagnesemia in 25.7%, hyperphosphatemia in 41.5%, decreased alkaline phosphatase serum activity in 28.7%, and hypercalciuria in 22.4% of cases. Surgical hypoparathyroidism is frequently accompanied by surgical hypothyroidism and injury to the recurrent laryngeal nerves. PMID:1669168

  1. 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

  2. Pathophysiology and treatment of nonfamilial hyperparathyroidism.

    PubMed

    Lumachi, Franco; Basso, Stefano M M

    2014-01-01

    Primary hyperparathyroidism (HPT) is the main cause of hypercalcemia and the most common parathyroid glands disease. The diagnosis is easy in patients with hypercalcemia and elevated PTH serum level. Minimally invasive parathyroidectomy (PTx) represents the treatment of choice for symptomatic patients, leading to several advantages, including immediate normalization of hypercalcemia and significant improvement of bone mineral density, cardiovascular dysfunctions, neuropsychological symptoms and quality of life. Secondary and tertiary HPT are relatively common complications in patients with chronic kidney disease (CKD) or advanced kidney failure, and in kidney transplant recipients who did not achieve complete calcium/phosphate metabolism normalization, respectively. The drugs available for patients with secondary HPT, and to treat hyperphosphatemia include non-calcium-containing phosphate binder, calcitriol analogues, calcimimetic agents, or a combination of two or more drugs. Although recent studies report that PTx significantly improves survival also in patients with CKD and severe secondary HPT, the indications for surgery are not yet well established. Subtotal or total PTx with or without autotransplantation are the surgical options for treating all patients with secondary HPT. Total PTx leads to a faster reduction in serum calcium level and normalization of PTH, but the risk of hypoparathyroidism is higher than after subtotal PTx. Further studies are needed to confirm the usefulness of the drugs currently recommended, and others will have to be tested in the near future. PMID:25643126

  3. The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

    PubMed Central

    Hebl, S.; Purnell, J. Q.; Reid, M. E.; Rosier, R. N.; Mustian, K. M.; Palesh, O. G.; Huston, A. J.; Ling, M. N.; Morrow, G. R.

    2010-01-01

    Summary Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. Introduction Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. Methods We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. Results and conclusion Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis. PMID:19960185

  4. Chemoprevention activity of 25-hydroxyvitamin D in the MMTV-PyMT mouse model of breast cancer.

    PubMed

    Rossdeutscher, Lionel; Li, Jiarong; Luco, Aimée-Lee; Fadhil, Ibtihal; Ochietti, Benoit; Camirand, Anne; Huang, Dao Chao; Reinhardt, Timothy A; Muller, William; Kremer, Richard

    2015-02-01

    Development of oncologic conditions is often accompanied by inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Because current effective vitamin D analogues, including the naturally occurring active metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D), frequently cause hypercalcemia at pharmacologic doses, the development of safer molecules for clinical chemopreventive use is essential. This study examines whether exogenously supplied prohormone 25-hydroxycholecalciferol (25(OH)D) can delay tumor progression in vivo without hypercalcemic effects. A low vitamin D diet (25 IU/kg) in the non-immunodeficient MMTV-PyMT mouse model of metastatic breast cancer revealed a significant acceleration of mammary neoplasia compared with normal diet (1,000 IU/kg). Systemic perfusion of MMTV-PyMT mice with 25(OH)D or 1,25(OH)2D delayed tumor appearance and significantly decreased lung metastasis, and both metabolites reduced Ki-67, cyclin D1, and ErbB2 levels in tumors. Perfusion with 25(OH)D caused a 50% raise in tumor 1,25(OH)2D levels, indicating good tumor penetration and effective activation. Importantly, in contrast with 1,25(OH)2D, perfusion with 25(OH)D did not cause hypercalcemia. In vitro treatment of cultured MMTV-PyMT mammary tumor cells with 25(OH)D inhibited proliferation, confirming local activation of the prohormone in this system. This study provides an in vivo demonstration in a non-immunodeficient model of spontaneous breast cancer that exogenous 25(OH)D delays neoplasia, tumor growth, and metastasis, and that its chemoprevention efficacy is not accompanied by hypercalcemia. PMID:25468832

  5. [A 38 years old female with inflammatory myofibroblastic tumor and lactic acidosis].

    PubMed

    Gorham, J; Liberale, G; Haydar, H Nasser; De Saint Aubain, N; Meert, A P

    2016-01-01

    Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally described in the lung, but they have been now observed in many others locations, mainly abdominal and pelvic. These tumors are usually benign but their recurrent nature and the presence of an abnormality of chromosome band 2p23 in some of them, suggest that some lesions form a true tumor entity. Surgical excision as complete as possible is the gold standard treatment. We report the case of a 38 years old female, who presented a recurrent metastasizing inflammatory myofibroblastic tumor causing lactic acidosis and other biological abnormalities such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular coagulation and inflammatory syndrome. PMID:27487696

  6. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  7. Absence of gallium-67 avidity in diffuse pulmonary calcification

    SciTech Connect

    Lecklitner, M.L.; Foster, R.W.

    1985-09-01

    Diffuse pulmonary uptake by bone-seeking radiopharmaceuticals has been reported previously but, in the same patient, would pulmonary uptake of Ga-67 citrate yield clinically meaningful results. A patient with hypercalcemia and renal failure in whom bone scintigraphy demonstrated striking diffuse bilateral pulmonary uptake, but subsequent gallium imaging demonstrated no evidence of pulmonary uptake greater than body background, is discussed. We conclude that pulmonary uptake of gallium cannot be attributed to calcium deposition and should carry the same clinical significance in regard to inflammatory and malignant lesions as would be assigned to patients without pulmonary calcific deposits.

  8. Evaluation of intense renal parenchymal activity (hot kidneys) on bone scintigraphy

    SciTech Connect

    Bernard, M.S.; Hayward, M.; Hayward, C.; Mundy, L. )

    1990-04-01

    The bone scintigrams of 600 patients performed over a 12-month period were reviewed. Thirty-six demonstrated abnormalities of the urinary tract of which six cases of intense renal parenchymal activity (hot kidneys) were found. Two cases were related to treatment with the new antineoplastic agent mitoxantrone. In one patient it was related to treatment with calcitonin. Neither of these associations has been previously reported. Recognized causes of hypercalcemia and recent radiotherapy were present in two patients. No cause could be found in the final patient.

  9. The pathophysiology of primary hyperparathyroidism.

    PubMed

    Brown, Edward M

    2002-11-01

    The parathyroid glands play a key role in maintaining near constancy of the extracellular calcium concentration ( Ca(o)2+) through their capacity to sense even minute changes in the level of blood calcium from its normal level. The G protein-coupled, Ca(o)(2+)-sensing receptor (CaSR) is the mechanism through which the parathyroid chief cells senses changes in Ca(o)2+. In primary hyperparathyroidism (PHPT), Ca(o)2+ is reset upward from its normal level. This defect likely arises from increases in both the mass of pathological parathyroid tissue as well as the set point for Ca(o)(2+)-regulated parathyroid hormone (PTH) release. The former likely arises from somatic mutations that enhance parathyroid cellular proliferation, although our understanding of the mechanism(s) underlying the latter is incomplete. However, substantial insights have been achieved through the study of inherited disorders caused by mutations in CaSR gene. In familial hypocalciuric hypercalcemia (FHH), heterozygous inactivating mutations in the CaSR gene produce mild, generally asymptomatic hypercalcemia, whereas in neonatal severe hyperparathyroidism (NSHPT), homozygous inactivating mutations cause severe hypercalcemia and hyperparathyroidism. Thus, the body's "calciostat" is reset upward in FHH and NSHPT because of resistance of CaSR-expressing cells, including the parathyroid cells, to Ca(o)2+. In FHH, there is a reduced complement of normal CaSRs (e.g., haploinsufficiency) that likely provides an explanation for the Ca(o)(2+)-resistance in this condition, whereas in NSHPT, there are no normally functioning CaSRs, thereby engendering more severe Ca(o)2+ resistance. Although somatic mutations in the CaSR gene could provide an explanation for the Ca(o)(2+)-resistance in PHPT, no such mutations have been found. Instead, in PHPT, the resistance of pathological parathyroid glands to Ca(o)2+ results, at least in part, from a reduced expression of otherwise apparently structurally normal CaSRs. Thus

  10. Syndromes that Link the Endocrine System and Genitourinary Tract.

    PubMed

    Özlük, Yasemin; Kılıçaslan, Işın

    2015-01-01

    The endocrine system and genitourinary tract unite in various syndromes. Genitourinary malignancies may cause paraneoplastic endocrine syndromes by secreting hormonal substances. These entities include Cushing`s syndrome, hypercalcemia, hyperglycemia, polycythemia, hypertension, and inappropriate ADH or HCG production. The most important syndromic scenarios that links these two systems are hereditary renal cancer syndromes with specific genotype/phenotype correlation. There are also some very rare entities in which endocrine and genitourinary systems are involved such as Carney complex, congenital adrenal hyperplasia and Beckwith-Wiedemann syndrome. We will review all the syndromes regarding manifestations present in endocrine and genitourinary organs. PMID:26177325

  11. Hypercalcemic encephalopathy due to milk alkali syndrome and injection teriparatide.

    PubMed

    Kharb, Sandeep; Gundgurthi, Abhay; Pandit, Aditi; Brar, Karninder S; Garg, M K

    2012-11-01

    An 82-year-old male, a known case of severe osteoporosis with vertebral fracture and prostatic carcinoma, was treated with gonadotropin releasing hormone analogue, calcium carbonate, cholecalciferol sachet and injection teriparatide. His diet consisted of milk and curd. He developed altered behavior and generalized weakness, and on investigation, hypercalcemia, hypokalemia, and metabolic alkalosis with low parathyroid hormone levels were detected. Injection teriparatide was stopped and he was managed with forced saline diuresis and injection zoledronic acid. He was diagnosed as a case of milk alkali syndrome in whom teriparatide and prolonged immobilization played a permissive role in the development of hypercalcemic encephalopathy. PMID:23226658

  12. Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Report of a Bilateral Case in a Teenager Associated with SMARCA4 Germline Mutation.

    PubMed

    Lavrut, Pierre-Marie; Le Loarer, François; Normand, Charline; Grosos, Céline; Dubois, Rémi; Buenerd, Annie; Conter, Cécile; Dijoud, Frédérique; Blay, Jean-Yves; Collardeau-Frachon, Sophie

    2016-01-01

    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive neoplasm that typically occurs in young females. Paraneoplastic hypercalcemia is associated in two thirds of the cases. Recent studies demonstrated that this rare tumor harbors the same molecular features of malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT with comprehensive molecular characterization in a 14-year-old girl. We also discuss the value of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies. PMID:26230154

  13. At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone

    PubMed Central

    Nickerson, Nicole; Riese, David J.; Hollenhorst, Peter C.; Lorch, Gwendolen; Foley, Anne M.

    2014-01-01

    The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone. PMID:22684584

  14. Transient thyrotoxicosis accompanied by panhypopituitarism caused by ruptured Rathke's cleft cyst.

    PubMed

    Chung, Jin Ook; Cho, Dong Hyeok; Chung, Dong Jin; Chung, Min Young

    2011-01-01

    We describe a rare case of transient thyrotoxicosis secondary to painless thyroiditis accompanied by panhypopituitarism caused by ruptured Rathke's cleft cyst. A 32-year-old man presented with vomiting and diarrhea. Laboratory data showed that he had transient hypercalcemia, primary thyrotoxicosis due to painless thyroiditis and panhypopituitarism. The sellar magnetic resonance imaging showed cystic macroadenoma. He underwent surgical exploration. Histological examination showed a ruptured Rathke's cleft cyst. Our case suggests that, although rare, it is important to recognize the possibility of coexistence of hypopituitarism in patients with primary thyrotoxicosis. PMID:22185992

  15. [Cognitive Function and Calcium. The link between dementia and bone and calcium metabolism disorders].

    PubMed

    Yamaguchi, Kiyoshi

    2015-02-01

    Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia. PMID:25634043

  16. [Nephropathy associated with electrolyte disorders].

    PubMed

    Tsuchiya, K; Nakauchi, M; Hondo, I; Nihei, H

    1995-08-01

    It is well known that renal dysfunction is associated with several types of electrolyte disorders. On the other hand, renal manifestations have been attributed to electrolyte disorders. Hypokalemia is the most frequent electrolyte abnormality encountered in clinical practice. The main cause of hypokalemia is due to abuse of laxatives and diuretics or to anorexia nervosa. Hypercalcemia is another major electrolyte abnormality, associated with numerous renal manifestations. Renal tubules damages and chronic interstitial nephritis are characteristic pathological findings in prolonged electrolyte disorders. The mechanism of renal involvement and characteristic clinical manifestations of the electrolyte disorders are reviewed. PMID:7563640

  17. Is calcium supplementation a risk factor for cardiovascular diseases in older women?

    PubMed

    Sabbagh, Zohreh; Vatanparast, Hassanali

    2009-02-01

    Low intake of dietary calcium is related to bone loss and fragility fracture in older adults, especially postmenopausal women. Contradictory findings have been reported from studies that investigated the association between calcium supplementation and hypertension and the risk of stroke and cardiovascular disease. Misinterpretation of findings from studies that are not primarily designed to address these issues might overshadow the benefits of dietary calcium. Until well-designed studies address the current uncertainties, the possible detrimental effect (e.g., hypercalcemia and its complications) of higher-than-recommended calcium intake should be balanced against the likely benefits of calcium on bone, particularly in elderly women. PMID:19178652

  18. Impact of Vitamin D on Chronic Kidney Diseases in Non-Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Xu, Lijuan; Wan, Xuesi; Huang, Zhimin; Zeng, Fangfang; Wei, Guohong; Fang, Donghong; Deng, Wanping; Li, Yanbing

    2013-01-01

    Background and Objectives Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. Design A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. Results Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, −0.10; 95%CI, −0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. Conclusions Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found. PMID:23626678

  19. A rare but significant cause of priapism in the elderly: multiple myeloma.

    PubMed

    Bahat, Gulistan; Tufan, Fatih; Akin, Sibel; Atay, Kadri; Saka, Bulent; Kutlu, Omer; Tascioglu, Cemil

    2011-01-01

    Priapism is a rare symptom with diverse etiological factors. Although most cases in adults are secondary to drug use and intracavernosal injections, blood dyscrasias and hypercoagulable states, vasculitis, penile metastases, neurological conditions, spider bites, carbon monoxide poisoning, and total parenteral nutrition may also result in priapism. We report a case of recurrent and refractory priapism in a 61-year-old man which was diagnosed as multiple myeloma after emergence of hypercalcemia and renal failure due to progression of the underlying pathology. The value of the initial diagnostic approach is emphasized. PMID:22526083

  20. [Adult T-cell lymphoma/leukemia associated with HTLV-I virus in Martinique: apropos of 2 cases].

    PubMed

    Gessain, A; Plumelle, Y; Sanhadji, K; Barin, F; Gazzolo, L; Constant-Desportes, M; Pascaline, N; Diebold, J; De-Thé, G

    1986-01-01

    Two HTLV-I associated adult T cell leukemia cases were observed in patient from Martinique (French West Indies). These case are similar to the clinical entity, described by Takatsuki in 1977 in Japan and by Catovsky in Caribbean patients, characterized by a lymphadenopathy, skin lesions and visceral involvement, hypercalcemia, an aggressive course, and poor prognosis. The malignant cells with T4 phenotype and often suppressive function, were pleomorphic, mature, with prominent nuclear irregularities. Systematic research of HTLV-I virus or antibodies in patients with this clinical picture, to measure the influence of this virus in T cell lymphoproliferative diseases in France and in French West Indies is required. PMID:3016639

  1. An adolescent case of familial hyperparathyroidism with a germline frameshift mutation of the CDC73 gene.

    PubMed

    Takeuchi, Takako; Yoto, Yuko; Tsugawa, Takeshi; Kamasaki, Hotaka; Kondo, Atsushi; Ogino, Jiro; Hasegawa, Tadashi; Yama, Naoya; Anan, Sawa; Uchino, Shinya; Ishikawa, Aki; Sakurai, Akihiro; Tsutsumi, Hiroyuki

    2015-10-01

    A 13-yr-old boy who complained of persistent nausea, vomiting and weight loss had hypercalcemia and an elevated intact PTH level. Computed tomography confirmed two tumors in the thyroid gland. The tumors were surgically removed and pathologically confirmed as parathyroid adenoma. Because his maternal aunt and grandmother both had histories of parathyroid tumors, genetic investigation was undertaken for him, and a germline frameshift mutation of the CDC73 gene was identified. CDC73 gene analysis should be done on individuals who are at risk of familial hyperparathyroidism, including those who are asymptomatic, and they should be followed for potential primary hyperparathyroidism and associated disorders including resultant parathyroid carcinoma. PMID:26568659

  2. [Pharmacovigilance update].

    PubMed

    Fogarasi Szabo, Nathalie; Diezi, Léonore; Delenclos, Laurie; Renard, Delphine; Chtioui, Haithem; Rothuizen, Laura E; Buclin, Thierry; Livio, Françoise

    2015-01-14

    The main pharmacovigilance updates in 2014 are reviewed. Ivabradine: increased risk of cardiovascular death and myocardial infarction in patients with symptomatic angina treated with high dosages. Clopidogrel: rare observations of acquired hemophilia. Orlistat: may reduce the absorption of HIV antiretrovirals. Ponatinib: increased risk of arteriopathy and thrombosis. Axitinib: significant risk of heart failure (class effect). Tocilizumab: possible causal relationship with the emergence or aggravation of psoriasis. Lithium: hypercalcemia and hyperparathyroidism commonly observed. Sildenalfil: suspected causal association with melanoma, so far not proven, Methylphenidate: rare observations of priapism. St John's wort (Hypericum): reduced effectiveness of hormonal contraceptives, including implants. PMID:25799668

  3. 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

  4. Ectopic parathyroid adenoma in child.

    PubMed

    Libánský, P; Astl, J; Adámek, S; Nanka, O; Pafko, P; Spacková, J; Foltán, R; Sedý, J

    2008-01-01

    A 10-year old girl presented with fatigue, hypercalcemia, and subperiosteal phalangeal osteolytic lesions. Ultrasonography and MIBI scintigraphy showed a structure near the lower pole of thyroid gland. The structure macroscopically appeared as adenoma, histologically it was thymic tissue. Bilateral neck exploration together with exploration of cervical thymic extensions was performed; adenoma was not found. During next two years, the level of calcium and parathormone raised, bone mineral density decreased. Ultrasonography, MRI, CT and PET/CT were negative. Adenoma was located by MIBI-SPECT/CT near the left border of jugulum. It was found dorsolateral to left common carotid artery and removed. PMID:19548602

  5. 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

  6. Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

    PubMed

    Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

    2013-09-01

    Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement. PMID:24079056

  7. Pseudohypoaldosteronism presenting with thrombocytosis and bilateral pneumothoraces in an infant.

    PubMed

    Javed, Asma; Leonard, Jennifer M; Cramer, Carl; Kumar, Seema; Kirmani, Salman; Brands, Chad K

    2013-01-01

    Pseudohypoaldosteronism type 1 (PHA-1) is a rare salt-wasting syndrome caused by a peripheral resistance to aldosterone. Here, we describe an unusual presentation of the autosomal dominant PHA-1 featuring bilateral pneumothoraces at birth, thrombocytosis in infancy, and hypercalcemia in addition to the well-described findings of hyponatremia, hyperkalemia, and failure to thrive. These findings contribute to the limited case descriptions of PHA-1 and may suggest additional diagnostic considerations in a neonate presenting with hyperkalemia, hyponatremia, and failure to thrive. PMID:23327809

  8. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover

    SciTech Connect

    Urban, Z.; Csiszar, K.; Boyd, C.D.

    1996-10-01

    Williams syndrome (WS) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile, characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hermas, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome 7q is associated with WS. Furthermore, two FISH studies using cosmid recombinants containing the 5{prime} or the 3{prime} end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases. However, the size of the 7q11.23 deletions and the mechanism by which these deletions arise are not known. 15 refs., 2 figs., 1 tab.

  9. 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

  10. Calcium-Alkali Syndrome in the Modern Era

    PubMed Central

    Patel, Ami M.; Adeseun, Gbemisola A.; Goldfarb, Stanley

    2013-01-01

    The ingestion of calcium, along with alkali, results in a well-described triad of hypercalcemia, metabolic alkalosis, and renal insufficiency. Over time, the epidemiology and root cause of the syndrome have shifted, such that the disorder, originally called the milk-alkali syndrome, is now better described as the calcium-alkali syndrome. The calcium-alkali syndrome is an important cause of morbidity that may be on the rise, an unintended consequence of shifts in calcium and vitamin D intake in segments of the population. We review the pathophysiology of the calcium-alkali syndrome. PMID:24288027

  11. [Does calcifediol replace vitamin D as a preventive and therapeutic agent?].

    PubMed

    Burmeister, W

    1984-07-01

    Cholecalciferol (CC) given orally is not utilized as efficiently as the CC produced by cutaneous UV light. The infant receives only minute amounts of CC by breast feeding, abolishing therefore the role of a vitamin for CC. The most important D-metabolite of human milk, the calcifediol (CF), however, has transient vitamin character. CF is both resorbed more efficiently by the intestine and it effects mineral metabolism faster via kidney than CC, which needs hydroxylation in the liver first. Thus CF shows advantages in prophylaxis and therapy. However, different (lower) dosages and the danger of hypercalcemia should be kept in mind using CF. PMID:6088972

  12. Cytologic Diagnosis of Heterobilharzia americana Infection in a Liver Aspirate From a Dog.

    PubMed

    Le Donne, V; McGovern, D A; Fletcher, J M; Grasperge, B J

    2016-05-01

    Heterobilharzia americanais a trematode of the Schistosomatidae family that infects dogs, raccoons, and other mammals as definitive hosts. This parasite is considered endemic in the southern Atlantic and Gulf coasts; however, only a few cases are reported. A 7-year-old dog from Louisiana was referred for persistent hypercalcemia, hyperglobulinemia, and weight loss. Abdominal ultrasound revealed diffuse hyperechogenicity of the liver with several hyperechoic nodules of varying size. Cytologic examination of fine-needle aspirates of the liver revealed few ovoid to round basophilic thin-walled eggshell fragments and rare ciliated miracidia.H. americanaeggs were identified on fecal sedimentation. PMID:26272209

  13. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

  14. An uncommon case showing three different pathologies on 99mtechnetium-methylene diphosphonate bone scintigraphy

    PubMed Central

    Chakraborty, Partha Sarathi; Karunanithi, Sellam; Dhull, Varun Singh; Kumar, Kunal; Gupta, Ravikant; Tripathi, Madhavi

    2015-01-01

    99mTechnetium-methylene diphosphonate bone scintigraphy (BS) has an important role in evaluating skeletal pathology, especially its extent. Incidental extra-osseous uptake may sometimes be seen in soft-tissue pathologies. We present a 64-year-old female with skull base osteomyelitis referred for BS which revealed involvement of the skull base on the left side, uptake was also noted in bilateral lungs secondary to hypercalcemia of renal failure and in the D12-L1 vertebrae as the patient had a history of Pott's spine. This is perhaps a unique case showing three findings each of a different etiology in the same scan. PMID:25589816

  15. HYPOALDOSTERONISM IN A MATSCHIE'S TREE KANGAROO (DENDROLAGUS MATSCHIEI).

    PubMed

    Whoriskey, Sophie T; Bartlett, Susan L; Baitchman, Eric

    2016-06-01

    A 20-yr-old female Matschie's tree kangaroo (Dendrolagus matschiei) was diagnosed with hypoaldosteronism, a rare condition in which the body fails to produce normal amounts of the mineralocorticoid aldosterone. Aldosterone plays a key role in body salt homeostasis, increasing sodium reabsorption and promoting excretion of potassium. Hypoaldosteronism resulted in decreased appetite, lethargy, and weight loss in conjunction with hyponatremia, hyperkalemia, and hypercalcemia in this tree kangaroo. The animal was successfully managed with mineralocorticoid replacement using desoxycorticosterone pivalate. To the authors' knowledge this is the first report of hypoaldosteronism in a tree kangaroo and one of the few reports in the veterinary literature in any species. PMID:27468039

  16. 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

  17. 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.

  18. Chronic Vitamin D Intoxication in Captive Iberian Lynx (Lynx pardinus)

    PubMed Central

    Muñoz, Luis; Raya, Ana; Lopez, Guillermo; Aguilera-Tejero, Escolástico

    2016-01-01

    To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets. PMID:27243456

  19. Chronic Vitamin D Intoxication in Captive Iberian Lynx (Lynx pardinus).

    PubMed

    Lopez, Ignacio; Pineda, Carmen; Muñoz, Luis; Raya, Ana; Lopez, Guillermo; Aguilera-Tejero, Escolástico

    2016-01-01

    To document the biochemical and pathologic features of vitamin D intoxication in lynx and to characterize mineral metabolism in healthy lynx, blood samples were obtained from 40 captive lynx that had been receiving excessive (approximately 30 times the recommended dose) vitamin D3 in the diet, and from 29 healthy free ranging lynx. Tissue samples (kidney, stomach, lung, heart and aorta) were collected from 13 captive lynx that died as a result of renal disease and from 3 controls. Vitamin D intoxication resulted in renal failure in most lynx (n = 28), and widespread extraskeletal calcification was most severe in the kidneys and less prominent in cardiovascular tissues. Blood minerals and calciotropic hormones in healthy lynx were similar to values reported in domestic cats except for calcitriol which was higher in healthy lynx. Changes in mineral metabolism after vitamin D intoxication included hypercalcemia (12.0 ± 0.3 mg/dL), hyperphosphatemia (6.3 ± 0.4 mg/dL), increased plasma calcidiol (381.5 ± 28.2 ng/mL) and decreased plasma parathyroid hormone (1.2 ± 0.7 pg/mL). Hypercalcemia and, particularly, hyperphosphatemia were of lower magnitude that what has been previously reported in the course of vitamin D intoxication in other species. However, extraskeletal calcifications were severe. The data suggest that lynx are sensitive to excessive vitamin D and extreme care should be taken when supplementing this vitamin in captive lynx diets. PMID:27243456

  20. [Primary hyperparathyroidism: diagnosis and management].

    PubMed

    Body, J J

    2012-09-01

    The prevalence of primary hyperparathyroidism (HPT) varies between 1 and 4/1.000 in the general population. HPT is nowadays most often asymptomatic. The classical bone disease has been replaced by osteopenia or osteoporosis with a preferential bone loss in cortical sites. The incidence of nephrolithiasis has been considerably lowered, but renal lithiasis is still the most frequent complication of HPT. The diagnosis is most often made by chance or during the workup of an abnormal bone mass. Hypercalcemia and an elevated PTH concentration, or at least a PTH level in the upper part of the normal range, generally point to a diagnosis of HPT. Additional tests include an evaluation of renal function, vitamin D measurement, determination of 24-hour urinary calcium and bone densitometry. Besides symptomatic HPT, classical recommendations for surgery include age less than 50, serum Ca at least 1 mg/dl above the upper limit of normal, creatinine clearance < 60 ml/min and osteoporosis. Surgical referral will, however, take into account patient age and comorbidities, as well as patient preferences. In the hands of an experienced surgeon, the success rate of parathyroidectomy is 95-98% and the rate of permanent complications is 1-3%. Parathyroid scintigraphy is the best preoperative localization technique of the adenoma. When surgery is contraindicated or refused by the patient, bisphosphonates or cinacalcet can be indicated in cases of osteoporosis or clinically significant hypercalcemia, respectively. PMID:23091930

  1. 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

  2. Pleiotropic effects of vitamin D in chronic kidney disease.

    PubMed

    Liu, Wen-Chih; Wu, Chia-Chao; Hung, Yao-Min; Liao, Min-Tser; Shyu, Jia-Fwu; Lin, Yuh-Feng; Lu, Kuo-Cheng; Yeh, Kun-Chieh

    2016-01-30

    Low 25(OH)D levels are common in chronic kidney disease (CKD) patients and are implicated in all-cause mortality and morbidity risks. Furthermore, the progression of CKD is accompanied by a gradual decline in 25(OH)D production. Vitamin D deficiency in CKD causes skeletal disorders, such as osteoblast or osteoclast cell defects, bone turnover imbalance, and deterioration of bone quality, and nonskeletal disorders, such as metabolic syndrome, hypertension, immune dysfunction, hyperlipidemia, diabetes, and anemia. Extra-renal organs possess the enzymatic machinery for converting 25(OH)D to 1,25(OH)2D, which may play considerable biological roles beyond the traditional roles of vitamin D. Pharmacological 1,25(OH)2D dose causes hypercalcemia and hyperphosphatemia as well as adynamic bone disorder, which intensifies vascular calcification. Conversely, native vitamin D supplementation reduces the risk of hypercalcemia and hyperphosphatemia, which may play a role in managing bone and cardio-renal health and ultimately reducing mortality in CKD patients. Nevertheless, the combination of native vitamin D and active vitamin D can enhance therapy benefits of secondary hyperparathyroidism because of extra-renal 1α-hydroxylase activity in parathyroid gland. This article emphasizes the role of native vitamin D replacements in CKD, reviews vitamin D biology, and summarizes the present literature regarding native vitamin D replacement in the CKD population. PMID:26656443

  3. Sporadic primary hyperparathyroidism.

    PubMed

    Blanchard, C; Mirallié, E; Mathonnet, M

    2010-10-01

    Primary hyperparathyroidism (HPT1) is a common endocrine disorder, which is asymptomatic in 80% of cases. The diagnosis is ordinarily easily made, based on an inappropriately elevated parathormone level (PTH) in the face of hypercalcemia. In 85% of cases, HPT1 is due to hormone secretion from a single parathyroid gland (uniglandular disease) and the remaining patients have multiglandular disease. The best localization study is MIBI scintigraphy (methoxy isobutyl isonitrile) coupled with the results of a neck ultrasound exam (sensitivity >95%). Other investigations are reserved for patients with persistent or recurrent HPT1 post-surgery. Surgery is the only cure. The surgical approach may include a bilateral cervical exploration, a unilateral approach under local anesthesia, or focused minimally invasive (video-assisted or totally endoscopic) approaches. A decrease in PTH level measured intraoperatively of greater than 50% is predictive of cure in more than 97% of cases. Surgery is recommended even for moderate HPT1 and for very elderly patients because improvement in both the quality of life and bone density have been proven in these situations. The role of medical treatment is limited. Persistent or recurrent HPT1 requires a meticulous diagnostic approach and management in surgical centers with expertise. Persistent elevation of PTH postoperatively without hypercalcemia does not mandate further exploration. The prognosis of normocalcemic patients with elevated postoperative PTH levels remains uncertain. PMID:20888315

  4. 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

  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. Glucocorticoid Regulation of the Vitamin D Receptor

    PubMed Central

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  7. Reversible vascular calcifications associated with hypervitaminosis D.

    PubMed

    Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

    2016-02-01

    A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D. PMID:26318020

  8. An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

    PubMed

    Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A

    2016-05-01

    Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given. PMID:26932179

  9. Multiple myeloma in a dog with multiple concurrent infectious diseases and persistent polyclonal gammopathy.

    PubMed

    Geigy, Caroline; Riond, Barbara; Bley, Carla Rohrer; Grest, Paula; Kircher, Patrick; Lutz, Hans

    2013-03-01

    A 12-year-old, spayed female, mixed-breed dog was presented for acute hematuria, stranguria, polyuria, and polydipsia, as well as lameness for 8 days. Previous medical history included treatment for infection with Ehrlichia canis, Anaplasma phagocytophilum, Leishmania infantum, and Dirofilaria immitis 6.5 years prior to presentation. Besides persistently increased antibody titers to E canis and A phagocytophilum, polyclonal gammopathy with a monoclonal spike and moderate hypercalcemia were observed. There was marked hematuria, and Staphylococcus aureus was cultured from urine. Two weeks after successful treatment of the urinary tract infection, radiographs showed an extensive destructive monostotic lesion of the right humerus. Cytologic examination of fine-needle aspirates of this lesion revealed a neoplastic round cell population suggestive of multiple myeloma. The dog was treated with melphalan and prednisolone for suspected multiple myeloma and doxycycline for suspected ehrlichiosis and anaplasmosis. Treatments lead to resolution of the clinical signs, hypercalcemia, and monoclonal gammopathy, and there was radiographic improvement of bone lesions; polyclonal gammopathy persisted. About one year after presentation the dog was still in clinical remission. This is a rare report of a dog with suspected multiple myeloma and a history of multiple chronic infectious diseases, suggesting that chronic infection and uncontrolled long-term stimulation of the immune system could contribute to the pathogenesis of multiple myeloma. PMID:23278475

  10. Primary hyperparathyroidism in pregnancy.

    PubMed

    Diaz-Soto, Gonzalo; Linglart, Agnès; Sénat, Marie-Victoire; Kamenicky, Peter; Chanson, Philippe

    2013-12-01

    Primary hyperparathyroidism (PHPT) is rarely diagnosed during pregnancy but is associated with significant maternal and fetal morbidity and mortality. Information on appropriate management is limited. We reviewed the medical literature through December 2012 for key articles on PHPT during pregnancy, focusing on large series. Clinical knowledge in this area is restricted to isolated case reports and a few retrospective studies. Diagnosis can be difficult, owing to the non-specific nature of signs and symptoms of hypercalcemia during pregnancy. Pregnant women with a calcium level over 2.85 mmol/L (11.4 mg/dL) and prior pregnancy loss are at a particularly high risk of maternal complications (hypercalcemic crisis, nephrolithiasis, pancreatitis, etc.) and fetal loss. Around one-half of neonates born to mothers with untreated PHPT have hypocalcemia and tetany. Algorithms proposed for the management of the pregnant woman with PHPT are not evidence based, reflecting the paucity of data. Treatment should thus be individually tailored. Gestational age and the severity of hypercalcemia should be taken into account when assessing the risk-benefit balance of a conservative approach (hyperhydration and vitamin D supplementation) versus parathyroid surgery. Current evidence supports parathyroidectomy as the main treatment, performed preferably during the second trimester, when the serum calcium is above 2.75 mmol/L (11 mg/dL). In the patients with mild forms of PHPT, which are nowadays the most frequent, a conservative management is generally preferred. PMID:23670708

  11. 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

  12. A nonclassical vitamin D receptor pathway suppresses renal fibrosis

    PubMed Central

    Ito, Ichiaki; Waku, Tsuyoshi; Aoki, Masato; Abe, Rumi; Nagai, Yu; Watanabe, Tatsuya; Nakajima, Yuka; Ohkido, Ichiro; Yokoyama, Keitaro; Miyachi, Hiroyuki; Shimizu, Toshiyuki; Murayama, Akiko; Kishimoto, Hiroyuki; Nagasawa, Kazuo; Yanagisawa, Junn

    2013-01-01

    The TGF-β superfamily comprises pleiotropic cytokines that regulate SMAD and non-SMAD signaling. TGF-β–SMAD signal transduction is known to be involved in tissue fibrosis, including renal fibrosis. Here, we found that 1,25-dihydroxyvitamin D3–bound [1,25(OH)2D3-bound] vitamin D receptor (VDR) specifically inhibits TGF-β–SMAD signal transduction through direct interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH)2D3 treatment prevented renal fibrosis through the suppression of TGF-β–SMAD signal transduction. Based on the structure of the VDR-ligand complex, we generated 2 synthetic ligands. These ligands selectively inhibited TGF-β–SMAD signal transduction without activating VDR-mediated transcription and significantly attenuated renal fibrosis in mice. These results indicate that 1,25(OH)2D3-dependent suppression of TGF-β–SMAD signal transduction is independent of VDR-mediated transcriptional activity. In addition, these ligands did not cause hypercalcemia resulting from stimulation of the transcriptional activity of the VDR. Thus, our study provides a new strategy for generating chemical compounds that specifically inhibit TGF-β–SMAD signal transduction. Since TGF-β–SMAD signal transduction is reportedly involved in several disorders, our results will aid in the development of new drugs that do not cause detectable adverse effects, such as hypercalcemia. PMID:24135137

  13. 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

  14. A dimer model of human calcitonin13-32 forms an α-helical structure and robustly aggregates in 50% aqueous 2,2,2-trifluoroethanol solution.

    PubMed

    Kawashima, Hiroyuki; Katayama, Mei; Yoshida, Ryota; Akaji, Kenichi; Asano, Akiko; Doi, Mitsunobu

    2016-07-01

    Determining the cause of human calcitonin (hCT) aggregation could be of help in the effort to utilize hCT for treatment of hypercalcemia. Here we report that a dimer model of hCT13-32 aggregated to a greater degree than native hCT under aqueous 2,2,2-trifluoroethanol conditions. Analyses using circular dichroism spectroscopy, thioflavine-T binding assays and atomic force microscopy suggest that the α-helical portion of hCT is important for initiation of the aggregation process, which yields long fibrils. Dimerization, which stabilizes the β-sheet structure of hCT, enhances aggregation potency. Dimerization of hCT stabilizes the α-helix under aqueous TFE conditions, leading to the long fibril formation. Up to now, there have been no reports of using a dimer model to investigate the properties of hCT aggregation. Our findings could potentially serve as the basis for development of novel hCT derivatives that could be utilized for treatment of hypercalcemia, as well as for development of novel therapeutics for other ailments caused by amyloid peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27238594

  15. Patient education for phosphorus management in chronic kidney disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2013-01-01

    Objectives: This review explores the challenges and solutions in educating patients with chronic kidney disease (CKD) to lower serum phosphorus while avoiding protein insufficiency and hypercalcemia. Methods: A literature search including terms “hyperphosphatemia,” “patient education,” “food fatigue,” “hypercalcemia,” and “phosphorus–protein ratio” was undertaken using PubMed. Results: Hyperphosphatemia is a strong predictor of mortality in advanced CKD and is remediated via diet, phosphorus binders, and dialysis. Dietary counseling should encourage the consumption of foods with the least amount of inorganic or absorbable phosphorus, low phosphorus-to-protein ratios, and adequate protein content, and discourage excessive calcium intake in high-risk patients. Emerging educational initiatives include food labeling using a “traffic light” scheme, motivational interviewing techniques, and the Phosphate Education Program – whereby patients no longer have to memorize the phosphorus content of each individual food component, but only a “phosphorus unit” value for a limited number of food groups. Phosphorus binders are associated with a clear survival advantage in CKD patients, overcome the limitations associated with dietary phosphorus restriction, and permit a more flexible approach to achieving normalization of phosphorus levels. Conclusion: Patient education on phosphorus and calcium management can improve concordance and adherence and empower patients to collaborate actively for optimal control of mineral metabolism. PMID:23667310

  16. [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

  17. X-ray microscopy studies on the pharmaco-dynamics of therapeutic gallium in rat bones

    SciTech Connect

    Bockman, R.; Repo, M.; Warrell, R.; Pounds, J.G.; Kwiatek, W.M.; Long, G.J.; Schidlovksy, G.; Jones, K.W.

    1987-01-01

    We describe here our preliminary results on gallium and calcium quantitation and localization using x-ray microscopy techniques at the X-26 beam line of the National Synchrotron Light Source (NSLS) at 50 to 100 ..mu..m resolution and 10/sup )minus/6) gg detection levels. Since the original observation of exogenous gallium accumulation in bones, several studies have demonstrated that gallium nitrate is extremely effective in preserving boen mienral content both in vivo and in vitro. Gallium nitrate therapy normalized serum calcium levels in a study of patients with caner-related hypercalcemia, resistant to standard hydration and diuretic therapy. Recently, gallium nitrate treatment has been shown to halt the accelerated bone resorption that is frequently associated with cancers metastatic to bone. Several lines of evidence from vitro studies recently led to the demonstration of increased bone calcium and improvement in hydroxyapatite crystallinity in adult gallium-treated rats. Evidence is rapidly accumulating that gallium nitrate is an effective, new therapeutic agent for inhibition of accelerated bone resorption associated with cancer-related hypercalcemia. It has also been suggested that gallium could have wide clinical applications in disorders characterized by accelerated calcium loss from bone. 7 refs., 3 figs., 1 tab

  18. The Abnormal Phenotypes of Cartilage and Bone in Calcium-Sensing Receptor Deficient Mice Are Dependent on the Actions of Calcium, Phosphorus, and PTH

    PubMed Central

    Tao, Chunxiang; Ding, Guoxian; Karaplis, Andrew; Brown, Edward; Goltzman, David; Miao, Dengshun

    2011-01-01

    Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)2D3 or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR–deficient (CaR−/−) mice to those of double homozygous CaR– and 1α(OH)ase–deficient [CaR−/−1α(OH)ase−/−] mice or those of double homozygous CaR– and PTH–deficient [CaR−/−PTH−/−] mice at 2 weeks of age. Compared to wild-type littermates, CaR−/− mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR−/− mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR−/− mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR−/− mice and that defects in endochondral bone formation in CaR−/− mice result from effects of the

  19. Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

    PubMed Central

    Ma, Yingyu; Yu, Wei-Dong; Hidalgo, Alejandro A.; Luo, Wei; Delansorne, Remi; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D₃ (1,25D₃) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D₃, inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)₂D₃; TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D₃, inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC₅₀ value 30 times lower than that of 1,25D₃. Both inecalcitol and 1,25D₃ induced a comparable level of G₀/G₁ cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D₃. Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D₃. In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D₃, in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D₃ vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a

  20. The abnormal phenotypes of cartilage and bone in calcium-sensing receptor deficient mice are dependent on the actions of calcium, phosphorus, and PTH.

    PubMed

    Liu, Jingning; Lv, Fangqiao; Sun, Wen; Tao, Chunxiang; Ding, Guoxian; Karaplis, Andrew; Brown, Edward; Goltzman, David; Miao, Dengshun

    2011-09-01

    Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)(2)D(3) or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR-deficient (CaR(-/-)) mice to those of double homozygous CaR- and 1α(OH)ase-deficient [CaR(-/-)1α(OH)ase(-/-)] mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-)PTH(-/-)] mice at 2 weeks of age. Compared to wild-type littermates, CaR(-/-) mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR(-/-) mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR(-/-) mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR(-/-) mice and that defects in endochondral bone formation in CaR(-/-) mice result from effects of the marked elevation in serum

  1. Quantitation of CYP24A1 Enzymatic Activity With a Simple Two-Hybrid System

    PubMed Central

    Mugg, Amy; Legeza, Balazs; Tee, Meng Kian; Damm, Izabella; Long, Roger K.

    2015-01-01

    Context: Mutations of the CYP24A1 gene encoding the 24-hydroxylase (24OHase) that inactivates metabolites of vitamin D can cause hypercalcemia in infants and adults; in vitro assays of 24OHase activity have been difficult. Objective: We sought an alternative assay to characterize a CYP24A1 mutation in a young adult with bilateral nephrolithiasis and hypercalcemia associated with ingestion of excess vitamin D supplements and robust dairy intake for 5 years. Methods: CYP24A1 exons were sequenced from leukocyte DNA. Wild-type and mutant CYP24A1 cDNAs were expressed in JEG-3 cells, and 24OHase activity was assayed by a two-hybrid system. Results: The CYP24A1 missense mutation L409S was found on only one allele; no other mutation was found in exons or in at least 30 bp of each intron/exon junction. Based on assays of endogenous 24OHase activity and of activity from a transiently transfected CYP24A1 cDNA expression vector, JEG-3 cells were chosen over HepG2, Y1, MA10, and NCI-H295A cells for two-hybrid assays of 24OHase activity. The apparent Michaelis constant, Km(app), was 9.0 ± 2.0 nm for CYP24A1 and 8.6 ± 2.2 nm for its mutant; the apparent maximum velocity, Vmax(app), was 0.71 ± 0.055 d−1 for the wild type and 0.22 ± 0.026 d−1 for the mutant. As assessed by Vmax/Km, the L409S mutant has 32% of wild-type activity (P = .0012). Conclusions: The two-hybrid system in JEG-3 cells provides a simple, sensitive, quantitative assay of 24OHase activity. Heterozygous mutation of CYP24A1 may cause hypercalcemia in the setting of excessive vitamin D intake, but it is also possible that the patient had another, unidentified CYP24A1 mutation on the other allele. PMID:25375986

  2. Primary Hyperparathyroidism in Pregnancy: A Two-Case Report and Literature Review

    PubMed Central

    Herrera-Martínez, A. D.; Bahamondes-Opazo, R.; Palomares-Ortega, R.; Muñoz-Jiménez, C.; Gálvez-Moreno, M. A.; Quesada Gómez, J. M.

    2015-01-01

    Primary hyperparathyroidism (PHPT) in pregnant women is an uncommon disease. It could be easily misdiagnosed because of physiologic changes during pregnancy; in some cases, patients could remain asymptomatic maintaining elevated calcium serum levels, and this situation represents a threat to the health of both mother and fetus. We present two cases of PHPT during pregnancy and their evolution after surgical treatment in the second trimester; there were no observed complications during pregnancy or delivery in our patients. Early diagnosis and medical/surgical treatment in PHPT are necessary for avoiding maternal and fetal complications which could not be predicted based on duration or severity of hypercalcemia. An appropriate management of PHPT during pregnancy is necessary for preserving the health of both the woman and the fetus. PMID:25893124

  3. Evaluation of radioactive phosphorus in the palliation of metastatic bone lesions from carcinoma of the breast and prostate

    SciTech Connect

    Cheung, A.; Driedger, A.A.

    1980-01-01

    Radioactive phosphorus effected substantial palliation of intractable bone pain in 17 of 33 (51.5%) women with metastatic carcinoma of the breast and in 14 of 15 (93.3%) men with metastatic carcinoma of the prostate. No significant difference in the overall response rate was found between androgen and paralthormone priming prior to radiophosphorus therapy. The degree of response was not dependent on total dose of /sup 32/P within the range of 9 to 18 mCi (333 to 666 MPq). Myelosuppression was a transient complication in 9 of 33 patients with metastatic breast carcinoma and in 7 of 15 patients with metastatic prostate carcinoma. Symptomatic hypercalcemia was an infrequent complication of radiophosphorus therapy irrespective of the priming regimen.

  4. Bilateral genu valgum: an unusual presentation of juvenile primary hyperparathyroidism

    PubMed Central

    Sharma, Shruti; Kumar, Sunil

    2016-01-01

    Primary hyperparathyroidism is a generalized disorder of bone and mineral metabolism caused by autonomous secretion of parathyroid hormone. It is primarily seen in adults with typical age of presentation between third and fifth decades of life. Juvenile hyperparathyroidism is a rare disorder. The common presentations in order of incidence are fatigue and lethargy, headache, nephrolithiasis, nausea, abdominal pain, vomiting and polydipsia. Though skeletal symptoms include bone pains and fractures, but the presence of limb deformity is atypical. We report a case of young girl who presented with isolated progressive genu valgum of both lower limbs and pigeon-shaped chest deformity. She was found to have hypercalcemia and hypophosphatemia with raised parathyroid hormone levels. The neck imaging showed a single adenoma in the left inferior parathyroid gland. The surgical removal of parathyroid adenoma was performed. PMID:27471596

  5. Mineral and bone disorder and vascular calcification in patients with chronic kidney disease.

    PubMed

    Peres, Luis Alberto Batista; Pércio, Pedro Paulo Verona

    2014-01-01

    Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders. PMID:25055361

  6. [Bisphosphonate-related osteonecrosis of the jaw].

    PubMed

    Atanes-Bonome, P; Atanes-Bonome, A; Ríos-Lage, P; Atanes-Sandoval, A D

    2014-04-01

    The bisphosphonates are stable inorganic pyrophosphate analogs that have demonstrated their efficacy in treatment of osteolytic lesions associated with bony metastases, and multiple myeloma, malignant hypercalcemia, Paget's disease, and osteoporosis. Several publications within the last few years have suggested that osteonecrosis of the jaw is associated with bisphosphonate therapy. The diagnosis and management strategies of the patients with bisphosphonate-related osteonecrosis of the jaw is very difficult. It is important for patients to be informed of the risk of this complication, so that they have the opportunity to assess the need for dental treatment before starting therapy. Preventive measures must be taken before, during, and after treatment with bisphosphonates. If osteonecrosis of the jaw is present, management should be conservative: oral chlorhexidine and antibiotics. Surgical treatment should be reserved for those patients who are symptomatic. PMID:24001573

  7. Space medicine considerations: Skeletal and calcium homeostasis

    NASA Technical Reports Server (NTRS)

    Schneider, Victor B.

    1989-01-01

    Based on the information obtained from space missions, particularly Skylab and the longer Salyut missions, it is clear that bone and mineral metabolism is substantially altered during space flight. Calcium balance becomes increasingly more negative throughout the flight, and the bone mineral content of the os calcis declines. The major health hazards associated with skeletal changes include the signs and symptoms of hypercalcemia with rapid bone turnover, the risk of kidney stones because of hypercalciuria, the lengthy recovery of lost bone mass after flight, the possibility of irreversible bone loss (particularly the trabecular bone), the possible effects of metastated calcification in the soft tissues, and the possible increase in fracture potential. For these reasons, major efforts need to be directed toward elucidating the fundamental mechanisms by which bone is lost in space and developing more effective countermeasures to prevent both short-term and long-term complications.

  8. [Normocalcemic primary hyperparathyroidism: a growing problem].

    PubMed

    Martínez Díaz-Guerra, Guillermo; Guadalix Iglesias, Sonsoles; Hawkins Carranza, Federico

    2013-08-01

    Normocalcemic primary hyperparathyroidism is at present one of the most common reasons for consultation in bone metabolism units. It is characterized by increased levels of intact parathyroid hormone in the presence of normal serum calcium (total and ionized) in generally asymptomatic individuals. The differential diagnosis should be considered in all situations that occur with secondary hyperparathyroidism. Its natural history is not well known, and it does not always progress to hypercalcemia. As a recently recognized entity, there are still no specific recommendations for its management. In this review we discuss some aspects of this entity, emphasizing the importance of a proper laboratory diagnosis, assessing possible signs or symptoms associated such as kidney stones or osteoporosis, which can help the clinician to take a conservative or interventionist attitude. PMID:23199831

  9. Successful treatment of Netherton's syndrome with topical calcipotriol.

    PubMed

    Godic, Aleksandar; Dragos, Vlasta

    2004-01-01

    We present a case of a 9-year-old boy with Netherton syndrome (NS) and skin manifestation of ichthyosis linearis circumflexa (ILC) who was successfully treated with topical 0.05% calcipotriol ointment bid. It was applied every fourth day on the same body area, which measured from 18% to 27% of the total body surface. Significant improvement of erythema and scaling was noted two weeks after the beginning of the treatment, with nearly total remission one week later, when the treatment was suspended. Remission lasted three to four weeks, when a few lesions of ILC appeared on his trunk and limbs and the treatment began again. The patient responded well each time he was treated. No adverse effects, suggestive of hypercalcemia or nephrocalcinosis, were noted during the treatment period which lasted for nine months. To evaluate calcipotriol's long-term efficacy and safety it should be tested on a larger group of patients with NS. PMID:15197002

  10. 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

  11. Vitamin D and Risk for Vitamin A Intoxication in an 18-Month-Old Boy

    PubMed Central

    Barreca, Massimo; Galiano, Rossella; Galati, Maria Concetta; Raiola, Giuseppe

    2016-01-01

    An 18-month-old boy presented with abdominal pain, vomiting, diarrhea, and poor appetite for 6 days. He had been given a multivitamin preparation once daily, containing 50.000 IU of vitamin D and 10.000 IU of vitamin A for a wide anterior fontanelle for about three months. He presented with hypercalcemia, low levels of parathyroid hormone (PTH), and very high serum 25-hydroxyvitamin D (25-OHD) levels. Renal ultrasound showed nephrocalcinosis. He did not have sign or symptom of vitamin A intoxication. Patient was successfully treated with intravenous hydration, furosemide, and prednisolone. With treatment, serum calcium returned rapidly to the normal range and serum 25-OHD levels were reduced progressively. In conclusion the diagnosis of vitamin D deficiency rickets without checking 25-OHD levels may cause redundant treatment that leads to vitamin D intoxication (VDI). PMID:27478669

  12. “The Great Mimicker”: An Unusual Etiology of Cytopenia, Diffuse Lymphadenopathy, and Massive Splenomegaly

    PubMed Central

    Zaarour, Mazen; Weerasinghe, Chanudi; Moussaly, Elias; Hussein, Shafinaz; Atallah, Jean-Paul

    2015-01-01

    Sarcoidosis is an idiopathic multisystem disease characterized by the formation of noncaseating granulomas. It frequently presents with pulmonary infiltrates and bilateral hilar and mediastinal lymphadenopathy. Splenic involvement is common, but massive splenomegaly is a rare occurrence. Sarcoidosis is known as “the great mimicker” (or “the great imitator”) since it exhibits a myriad of symptoms, mimicking other inflammatory, infectious, and neoplastic conditions, including lymphoma. Herein, we report the case of a 44-year-old male patient who was found to have bicytopenia, hypercalcemia, diffuse lymphadenopathy, and massive splenomegaly, a constellation of findings suggestive of underlying lymphoma. Interestingly, lymph node biopsy showed noncaseating granulomas suggestive of sarcoidosis, without evidence of malignancy. PMID:26579198

  13. Osteonecrosis of the Torus Palatinus in the Setting of Long-Term Oral Bisphosphonate Use--A Case Report.

    PubMed

    Ryan, Joshua L; Larson, Eric

    2016-01-01

    Bisphosphonates are medications used orally and intravenously for a variety of conditions including cancer metastatic to bone, hypercalcemia of malignancy, Paget's disease and osteoporosis. Osteonecrosis of the jaw has been related to bisphosphonate use. Osteonecrosis of the jaw most commonly occurs in the setting of intravenous bisphosphonate use and concomitant dental work or trauma. Oral bisphosphonates have much less risk of osteonecrosis of the jaw. We present an interesting case of a patient on an oral bisphosphonate for an extended period of time (nine years), with a torus palatinus, who burned her palate while eating a slice of pizza. Over six months later, she presented with an area of denuded bone and diagnosis consistent with osteonecrosis of the torus palatinus. PMID:26882578

  14. Massive Retroperitoneal Hemorrhage as an Initial Presentation of a Rare and Aggressive Form of Multiple Myeloma

    PubMed Central

    Alawadhi, Aydah; Leb, Laszlo

    2016-01-01

    Multiple myeloma, a plasma cell neoplasm, presents most commonly with anemia, hypercalcemia, renal failure, and bone pain. Only few cases of clinical aggressive presentation associated with bleeding were reported in the medical literature. The reported cases included gastrointestinal bleeding and cardiac tamponade. Spontaneous retroperitoneal haemorrhage as initial presentation has not been so far reported. We hereby report a case of a 64-year-old female who was found to have catastrophic hemorrhage in the retroperitoneal region that extended into intrathecal space causing cord compression. The case posed a significant diagnostic and management dilemma. This case emphasizes the need to think broadly and include multiple myeloma in the diagnosis of unexplained massive retroperitoneal bleeding. PMID:26885415

  15. Primary hyperparathyroidism

    PubMed Central

    Madkhali, Tarıq; Alhefdhi, Amal; Chen, Herbert; Elfenbein, Dawn

    2016-01-01

    Primary hyperparathyroidism is a common endocrine disorder caused by overactivation of parathyroid glands resulting in excessive release of parathyroid hormone. The resultant hypercalcemia leads to a myriad of symptoms. Primary hyperparathyroidism may increase a patient’s morbidity and even mortality if left untreated. During the last few decades, disease presentation has shifted from the classic presentation of severe bone and kidney manifestations to most patients now being diagnosed on routine labs. Although surgery is the only curative therapy, many advances have been made over the past decades in the diagnosis and the surgical management of primary hyperparathyroidism. The aim of this review is to summarize the characteristics of the disease, the work up, and the treatment options. PMID:26985167

  16. Mechanisms of radio-protection by catecholamines in the hamster /Mesocricetus auratus/

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Musacchia, X. J.

    1975-01-01

    Experiments were conducted on normal and splenectomized male and female hamsters between 2 and 3 months old subjected to a whole-body exposure of 1000 or 2000 rads in a Co-60 source with a view toward evaluating their radio-protection by norepinephrine, isoproterenol, and phenylephrine. Vasoconstriction hypoxia mechanism of radio-protection is examined along with the hypothesis that isoproterenol protects by hypercalcemia-induced cell proliferation. Radiation experiment results are found to be consistent with the hypothesis that stimulation of alpha receptors results in radio-protection through a tissue hypoxia mechanism. Beta agonists seem to protect by a hypotensive-hypoxia mechanism. The catecholamines protect against the hematopoietic syndrome, but show no evidence of protection against the gastrointestinal syndrome.

  17. Bone and body mass changes during space flight

    NASA Astrophysics Data System (ADS)

    Schneider, V.; Oganov, V.; LeBlanc, A.; Rakmonov, A.; Taggart, L.; Bakulin, A.; Huntoon, C.; Grigoriev, A.; Varonin, L.

    Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.

  18. Multisystemic Side Effects of an Indispensable Old Drug: A Case Report of Chronic Lithium Use (A Patient with Multiple Side Effects of Lithium)

    PubMed Central

    Demirtas, Levent; Akbas, Emin Murat; Degirmenci, Husnu; Gurel, Ali; Duzgun, Eren

    2015-01-01

    Presented here is a case of long-term lithium use, with multiple emerging lithium-associated side effects. An 82-year-old woman was brought into the emergency department because of loss of consciousness. According to the physical examination and laboratory analyses, patient was diagnosed with lithium-associated hypercalcemia, hyperparathyroidism, nephrogenic diabetes insipidus (NDI), symptomatic sinus bradycardia, and thyroid dysfunction. In the literature, there is a limited number of case reports with lithium induced multiple clinical conditions. Multiple clinical manifestations due to the side effects of chronic lithium use might be seen. Health care professionals should keep in mind that lithium-related side effects might trigger or exacerbate each other. To avoid toxicity, close follow-up and clinical supervision are important for the early diagnosis and treatment of these side effects, due to the narrow therapeutic index and obscure clinical signs and symptoms of toxicity. PMID:26604931

  19. Influence of prednisolone on urinary calcium oxalate and struvite relative supersaturation in healthy young adult female domestic shorthaired cats.

    PubMed

    Geyer, Nicole; Bartges, Joseph W; Kirk, Claudia A; Cox, Sherry; Hezel, Alisha; Moyers, Tammy; Hayes, Jimmy

    2007-01-01

    Prednisolone (10 mg PO q24h) or placebo was administered to healthy cats for 2 weeks in a masked, placebo-controlled, crossover-design study, and 24-hour urine samples were collected. When cats received prednisolone, 24-hour urine pH was lower and 24-hour urine excretion of creatinine, magnesium, phosphate, and potassium was higher than when cats received placebo. No significant difference was found in urinary relative supersaturation for calcium oxalate (CaOx) or struvite between treatment groups. Prednisolone administration did not induce diuresis, nor was it associated with increased calcium excretion or urinary saturation for CaOx in these healthy cats. Results of this study, however, should not be extrapolated to cats that form CaOx uroliths associated with idiopathic hypercalcemia. PMID:18183542

  20. Vitamin D: Pharmacokinetics and Safety When Used in Conjunction with the Pharmaceutical Drugs Used in Cancer Patients: A Systematic Review

    PubMed Central

    Kennedy, Deborah A.; Cooley, Kieran; Skidmore, Becky; Fritz, Heidi; Campbell, Tara; Seely, Dugald

    2013-01-01

    Vitamin D has reported anti-cancer and anti-inflammatory properties modulated through gene transcription and non-genomic signaling cascades. The purpose of this review was to summarize the available research on interactions and pharmacokinetics between vitamin D and the pharmaceutical drugs used in patients with cancer. Hypercalcemia was the most frequently reported side effect that occurred in high dose calcitriol. The half-life of 25(OH)D3 and/or 1,25(OH)2D3 was found to be impacted by cimetidine; rosuvastatin; prednisone and possibly some chemotherapy drugs. No unusual adverse effects in cancer patients; beyond what is expected from high dose 1,25(OH)2D3 supplementation, were revealed through this review. While sufficient evidence is lacking, supplementation with 1,25(OH)2D3 during chemotherapy appears to have a low risk of interaction. Further interactions with vitamin D3 have not been studied. PMID:24216707

  1. Nuclear Imaging and Minimally Invasive Surgery in the Management of Hyperparathyroidism*

    PubMed Central

    Judson, Benjamin L.; Shaha, Ashok R.

    2013-01-01

    Primary hyperparathyroidism is the most common cause of hypercalcemia, and the treatment is primarily surgical. Because of biochemical screening, more patients now present with asymptomatic primary hyperparathyroidism, and consensus guidelines have been developed for the treatment of these patients. There is now considerable interest in minimally invasive approaches to the treatment of hyperparathyroidism. Sestamibi scanning as a localizing study, used in combination with anatomic imaging and intraoperative rapid parathyroid hormone assays, has enabled focused surgical approaches. Patients with localizing studies that indicate a single parathyroid adenoma are candidates for such approaches, including unilateral neck exploration, minimally invasive single-gland exploration, or endoscopic exploration instead of the traditional approach of bilateral neck exploration. Nuclear imaging is also critical to the successful management of patients with persistent or recurrent hyperparathyroidism. PMID:18927330

  2. [Renal osteodystrophy (3); its treatment in dialysis patients].

    PubMed

    Ghitu, S; Oprisiu, R; Benamar, L; Said, S; Tataru Albu, A; Arsenescu, I; el Esper, N; Morinière, P; Fournier, A

    2000-01-01

    The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D

  3. Acute Necrotizing Pancreatitis Following Olanzapine Treatment and 759C/T Polymorphism of HTR2C Gene: A Case Report.

    PubMed

    Rizos, Emmanouil; Tournikioti, Kalliopi; Alevyzakis, Evangelos; Peppa, Melpomeni; Papazaxos, Konstantinos; Zorbas, Georgios; Michopoulos, Ioannis; Liappas, Ioannis; Papageorgiou, Charalampos; Douzenis, Athanasios

    2015-01-01

    Acute pancreatitis can be attributed to numerous potential causes, such as alcohol abuse, chololithiasis, infection, lesions, tumors, hypercalcemia, hyperlipidemia, and medications. Among psychotropic medications, the use of some atypical antipsychotics, such as clozapine, olanzapine, quetiapine and risperidone, has been implicated in the development of acute pancreatitis, although the underlying mechanism has not been clarified. We describe the case of a young man with no other major medical problems, alcohol abuse or predisposing factors, who developed acute necrotizing pancreatitis following olanzapine administration, possibly through severe elevation of serum triglycerides. A pharmacogenomic analysis revealed the presence of the 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled (HTR2C) -759C genotype which is related to increased risk for metabolic syndrome. PMID:26359410

  4. [Dw-MRI and bone scintigraphy in monitoring radio-therapy response in bone metastases].

    PubMed

    Raucci, Antonio; Gatta, Gianluca; Cuccurullo, Vincenzo

    2012-11-01

    Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. Diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to radiotherapy in bone metastases patients. The addition of DWI to conventional whole-body MRI sequences enhanced lesion conspicuity and improved diagnostic accuracy. We evaluate bone metastases patients with bone scintigraphy and DW-MRI. With technical optimization, whole-body MRI with DWI, as a nonionizing imaging modality, may potentially be useful as an alternative method to bone scintigraphy in the management of bone metastases. PMID:23096728

  5. Bisphosphonates: mechanism of action and role in clinical practice.

    PubMed

    Drake, Matthew T; Clarke, Bart L; Khosla, Suneep

    2008-09-01

    Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclast-mediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use. PMID:18775204

  6. Granulomatous Lithiasic Cholecystitis in Sarcoidosis

    PubMed Central

    Handra-Luca, Adriana

    2016-01-01

    Gallbladder granulomas are exceedingly rare, reported in association with tuberculosis or sarcoidosis. Here we report a case of gallbladder granulomatous cholecystitis occurring in the context of sarcoidosis. A 70-years old man presented with abdominal pain, nausea and vomiting. The medical history revealed sarcoidosis diagnosed more than 20-years previously. 2-years previously the patient showed renal lithiasis, hypercalcemia and, increased angiotensin converting enzyme. The imaging features suggested thoraco-abdominal sarcoidosis. Prednisone was given at 1.2 mg/kg/day initially, than decreased, being at 2.5 mg/day at present. The ultrasound examination showed gallbladder lithiasis. A cholecystectomy was performed. Microscopy showed subacute and chronic cholecystitis with several epithelioid and giant cell granulomas some of them perineural. In conclusion, we report a case of granulomatous cholecystitis occurring in the course of treated sarcoidosis. The perineural location of granulomas may give further insights into the pathogenesis of gallbladder dysmotility. PMID:27162601

  7. Paraneoplastic syndromes in olfactory neuroblastoma

    PubMed Central

    Gabrych, Anna; Czapiewski, Piotr; Sworczak, Krzysztof

    2015-01-01

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature. PMID:26199564

  8. Hypophosphatasia.

    PubMed

    Linglart, Agnès; Biosse-Duplan, Martin

    2016-06-01

    Hypophosphatasia is a rare disorder due to a mutation in the ALPL gene encoding the alkaline phosphatase (ALP) leading to a diminished activity of the enzyme in bone, liver, and kidney. Hypophosphatasia is a heterogeneous disease, ranging from extreme life-threatening forms revealed at birth in young infants presenting with severely impaired bone mineralization, seizures, and hypercalcemia, to young adults with premature exfoliation of their teeth without any other symptom. We will review the challenges of the clinical, biochemical, radiological, and genetic diagnosis. Schematically, the diagnosis relies on low ALP levels and, in most cases, on the genetic defect in the ALPL gene. An enzyme replacement therapy is now developed for hypophosphatasia; early results in the severe form of the disease are extremely encouraging. However, multidisciplinary care remains the core of treatment of hypophosphatasia encompassing nutritional support, adjustment of calcium and phosphate intake, monitoring of vitamin D levels, careful and personalized physical therapy, and regular dental monitoring and care. PMID:27084188

  9. Reader's digest of the pathophysiology of bone metastases.

    PubMed

    Gruber, Reinhard

    2012-09-01

    Bone metastases are a process originally proposed as the "seed and soil theory" in the eighteenth century. Tumor cell disseminating from patients with breast or prostate cancer typically use the bony environment to grow outside the primary tumor location. The severe clinical consequences of bone metastasis such as pain, fractures, and hypercalcemia result from a serious misbalance of bone turnover. Most bone metastases cause catabolic changes of bone turnover. The severity of bone resorption is associated with tumor growth, suggesting the existence of a vicious cycle that needs to be interrupted. Osteoblastic metastasis showing signs of osteosclerotic lesions are observed in prostate cancer. Understanding the pathophysiology of bone metastases and their detrimental consequence provide the scientific basis for therapeutic interventions at various levels including homing of tumors to bone, survival and growth of the tumor cell in the bone niche, and the mechanisms causing bone destruction. PMID:22797871

  10. 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

  11. 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

  12. [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

  13. Novel agents in the treatment of multiple myeloma: a review about the future.

    PubMed

    Naymagon, Leonard; Abdul-Hay, Maher

    2016-01-01

    Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the novel agents that are being studied or have recently been approved for the treatment of MM. These agents include the following: immunomodulators (pomalidomide), proteasome inhibitors (carfilzomib, marizomib, ixazomib, oprozomib), alkylating agents (bendamustine), AKT inhibitors (afuresertib), BTK inhibitors (ibrutinib), CDK inhibitors (dinaciclib), histone deacetylase inhibitors (panobinostat, rocilinostat, vorinostat), IL-6 inhibitors (siltuximab), kinesin spindle protein inhibitors (filanesib), monoclonal antibodies (daratumumab, elotuzumab, indatuximab, SAR650984), and phosphoinositide 3-kinase (PI3K) inhibitors. PMID:27363832

  14. The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors.

    PubMed

    Lipton, Allan; Uzzo, Robert; Amato, Robert J; Ellis, Georgiana K; Hakimian, Behrooz; Roodman, G David; Smith, Matthew R

    2009-10-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  15. PTHrP Gene Expression in Cancer: Do All Paths Lead to Ets?

    PubMed Central

    Richard, Virgile; Rosol, Thomas J.; Foley, John

    2010-01-01

    Parathyroid hormone-related protein (PTHrP) came to the attention of the scientific community in the mid-1980s because of its association with the paraneoplastic syndrome of humoral hypercalcemia of malignancy. Recently, a crucial role for the peptide has been identified in the metastatic growth of cancer cells in bone. Efforts to understand the peptide’s role in these pathological processes have evolved into the study of PTHrP gene expression. Currently, regulation of the third PTHrP promoter is beginning to be understood in the context of activation of certain signaling pathways involved in the growth and progression of specific neoplasms. In addition, factors that modulate the entire PTHrP-transcriptional unit, as well as the stability of the mRNA, are being elucidated at the level of cis-acting sequences. PMID:16022632

  16. [Derangements of mineral metabolism associated with tumors].

    PubMed

    Fukumoto, Seiji

    2014-08-01

    Bone as a hard tissue has several functions such as supporting our body and protecting internal organs. In addition, bone has a pivotal role in the regulation of circulatory mineral concentrations. Therefore, abnormal bone metabolism is sometimes accompanied by deranged serum calcium or phosphate levels as shown in patients with malignancy-associated hypercalcemia (MAH) or tumor-induced osteomalacia (TIO) . Parathyroid hormone-related protein, PTHrP, was cloned as a major humoral factor causing MAH. Similarly, fibroblast growth factor 23, FGF23, was identified as a causative factor for TIO. Therefore, MAH and TIO are not only important in clinical practice but also gave us deep insights into the mechanisms of mineral homeostasis, and bone and cartilage metabolism. PMID:25065866

  17. Metastatic ductal adenocarcinoma in a Western Hognose snake (Heterodon nasicus).

    PubMed

    Stern, Adam W; Velguth, Karen E; D'Agostino, Jennifer

    2010-06-01

    A 17-yr-old Western Hognose snake (Heterodon nasicus) presented with a prominent midcoelomic swelling. Surgical exploration revealed a large, multicystic, irregular, tan, and firm mass grossly effacing the splenopancreas. The mass was subsequently removed. Histologically, the mass was composed of tubules of columnar to flattened neoplastic cells with an abundant stroma and moderate cellular atypia consistent with a scirrhous adenocarcinoma, likely ductal in origin, given the location of the neoplastic mass. Bloodwork revealed anemia, monocytosis, marked hypercalcemia, and, postoperatively, persistent hyperglycemia. After postoperative recovery, the snake was diagnosed with iatrogenically induced diabetes mellitus and exocrine pancreatic insufficiency. Due to the inability to clinically control the diabetes mellitus and exocrine pancreatic insufficiency and when additional palpable masses were noted, the snake was euthanatized. Necropsy and histopathologic examination confirmed metastasis of the previously removed adenocarcinoma to the liver, right kidney, and large intestine. PMID:20597225

  18. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    PubMed Central

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M.; Dhanasekaran, Saravana; Mehra, Rohit

    2015-01-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery. PMID:26793516

  19. The multifaceted actions of PTHrP in skeletal metastasis

    PubMed Central

    Soki, Fabiana N; Park, Serk In; McCauley, Laurie K

    2012-01-01

    PTHrP, identified during the elucidation of mediators of malignancy-induced hypercalcemia, plays numerous roles in normal physiology as well as pathological conditions. Recent data support direct functions of PTHrP in metastasis, particularly from tumors with strong bone tropism. Bone provides a unique metastatic environment because of mineralization and the diverse cell populations in the bone marrow. PTHrP is a key regulator of tumor–bone interactions and regulates cells in the bone microenvironment through proliferative and prosurvival activities that prime the ‘seed’ and the ‘soil’ of the metastatic lesion. This review highlights recent findings regarding the role of PTHrP in skeletal metastasis, including direct actions in tumor cells, as well as alterations in the bone microenvironment and future perspectives involving the potential roles of PTHrP in the premetastatic niche, and tumor dormancy. PMID:22830401

  20. 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.

  1. Enhancement of the antiparakeratotic potency of calcitriol and tacalcitol in liposomal preparations in the mouse tail test.

    PubMed

    Körbel, J N; Sebök, B; Kerényi, M; Mahrle, G

    2001-01-01

    In order to test the advantage of vitamin D(3) preparations in liposomal form, calcitriol, the natural activated form of vitamin D(3), and tacalcitol, a vitamin D(3) analogue, were employed in various concentrations and using different vehicles in the mouse tail test, an animal model for testing the antiparakeratotic efficacy of topical medications. The optimal concentration in petrolatum turned out to be similar to that in commercial preparations. The liposomal preparations were superior to those in petrolatum and to those in nonliposomal phospholipids. The antiparakeratotic potency (drug activity) of liposomal tacalcitol in a concentration of 2 microg/g was twice that of the commercial preparation with a higher concentration of 4 microg/g. These results suggest that the use of liposomal vitamin D(3) preparations can achieve a given antipsoriatic effect with a reduced concentration of the active substance thereby reducing the risk of skin irritation and of hypercalcemia. PMID:11586070

  2. Acute renal failure in patients with multiple myeloma.

    PubMed

    Cohen, D J; Sherman, W H; Osserman, E F; Appel, G B

    1984-02-01

    In the past, patients with multiple myeloma and acute renal failure have had a poor prognosis. Few patients recovered renal function and fewer still survived for prolonged time periods. This report describes the course of 10 patients with multiple myeloma and true acute renal failure treated during the decade 1970 to 1980, and reviews recent reports concerning this association. The use of radiographic contrast agents is no longer the primary predisposing factor to acute renal failure in the myeloma population. Rather, infection, hypercalcemia, and dehydration in the presence of light chain excretion are the major conditions precipitating the renal failure. Despite severe renal failure requiring dialysis, many patients may regain good renal function. Factors associated with a good or poor prognosis in this population are reviewed. The prognosis in patients with myeloma and acute renal failure has greatly improved in recent years, and prolonged survival may occur. PMID:6695948

  3. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    PubMed

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma. PMID:24317268

  4. Congenital mastoid cholesteatoma presenting as a mass obstructing external auditory canal.

    PubMed

    Khairunnisak, M; Mohd Khairi, M D

    2014-12-01

    We describe the clinical presentation, investigation and management of an eventually fatal case of hypercalcemic crisis due to primary hyperparathyridism (PHPT). A 60 year-old lady with history of urolithiasis presented with worsening generalized bone pain, spinal scoliosis and a limp. Laboratory data showed hypercalcemia and raised alkaline phosphatase. Left hip x-ray revealed a subcapital femoral neck fracture. Intact parathyroid hormone was elevated, 187.6 pmol/L (1.6 - 6.9) and ultrasound showed an enlarged right parathyroid gland. Despite initial reduction of serum calcium with saline infusion and multiple doses of intravenous pamidronate, her calcium increased to 4.14 mmol/L a week following application of Buck's traction for persistent left hip pain. She succumbed eventually with serum calcium peaking at 6.28 mmol/L despite multiple therapeutic interventions. PMID:25934960

  5. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  6. Transmucosal delivery systems for calcitonin: a review.

    PubMed

    Torres-Lugo, M; Peppas, N A

    2000-06-01

    The commercial availability of peptides and proteins and their advantages as therapeutic agents have been the basis for tremendous efforts in designing delivery systems for such agents. The protection of these agents from biological fluids and physiological interactions is crucial for the treatment efficacy. One such agent is salmon calcitonin, a 32 amino-acid polypeptide hormone used in the treatment of bone diseases such as Paget's disease, hypercalcemia and osteoporosis. Researchers have studied different routes to deliver salmon calcitonin more effectively, including nasal, oral, vaginal and rectal delivery. These systems are designed to protect the polypeptide from the biological barriers that each delivery route imposes. Oil-based and polymer-based delivery systems are discussed. PMID:10811300

  7. Molecular regulation of osteoclast activity.

    PubMed

    Bruzzaniti, Angela; Baron, Roland

    2006-06-01

    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed. PMID:16951988

  8. Williams syndrome starts making sense

    SciTech Connect

    Ashkenas, J.

    1996-10-01

    1996 may be marked as a transitional year in the study of Williams syndrome (WS), when the causes of this complex condition and a practical way to investigate began to come into focus. WS presents a remarkable collection of symptoms that affect blood vessels, growth, intelligence, and behavior. WS commonly leads to infantile hypercalcemia, retardation of growth, prematurely wrinkled skin, supraventricular aortic stenosis (SVAS), and sensitivity to loud noise. Children with this condition are often mentally retarded, with distinctive {open_quotes}elfin{close_quotes} facial features, a hoarse voice, and an {open_quotes}engaging{close_quotes} personality. Their cognitive deficits may be minimal or profound but typically involve a specific pattern of strengths and weaknesses, with better-than-average face recognition but little ability to recognize how parts of patterns that they see fit into a whole. 36 refs.

  9. International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation

    PubMed Central

    Palumbo, Antonio; Rajkumar, S. Vincent; San Miguel, Jesus F.; Larocca, Alessandra; Niesvizky, Ruben; Morgan, Gareth; Landgren, Ola; Hajek, Roman; Einsele, Hermann; Anderson, Kenneth C.; Dimopoulos, Meletios A.; Richardson, Paul G.; Cavo, Michele; Spencer, Andrew; Stewart, A. Keith; Shimizu, Kazuyuki; Lonial, Sagar; Sonneveld, Pieter; Durie, Brian G.M.; Moreau, Philippe; Orlowski, Robert Z.

    2014-01-01

    Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. PMID:24419113

  10. The role of RANK-ligand inhibition in cancer: the story of denosumab.

    PubMed

    Castellano, Daniel; Sepulveda, Juan Manuel; García-Escobar, Ignacio; Rodriguez-Antolín, Alfredo; Sundlöv, Anna; Cortes-Funes, Hernán

    2011-01-01

    The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular. PMID:21285392

  11. Prognosis of metastatic renal cell carcinoma with first-line interferon-α therapy in the era of molecular-targeted therapy.

    PubMed

    Kawano, Yoshiaki; Takahashi, Wataru; Eto, Masatoshi; Kamba, Tomomi; Miyake, Hideaki; Fujisawa, Masato; Kamai, Takao; Uemura, Hirotsugu; Tsukamoto, Taiji; Azuma, Haruhito; Matsubara, Akio; Nishimura, Kazuo; Nakamura, Tsuyoshi; Ogawa, Osamu; Naito, Seiji

    2016-07-01

    The RCC-SELECT study showed the correlation between single nucleotide polymorphisms (SNP) in STAT3 gene and survival in metastatic renal cell carcinoma (mRCC) patients with first-line interferon-α (IFN-α). In that study, even patients with STAT3 SNP linked to shorter overall survival (OS) exhibited remarkably improved prognosis. All 180 patients evaluated in the above study were further analyzed for correlation between OS and demographics/clinicopathological parameters. OS was estimated using the Kaplan-Meier method. Associations between OS and potential prognostic factors were assessed using the log-rank test and the Cox proportional hazards model. The median OS was 42.8 months. Univariate analysis showed that worse Eastern Cooperative Oncology Group-performance status (ECOG-PS), high T stage, regional lymph node metastasis, distant metastasis, higher grade, infiltrative growth pattern, the presence of microscopic vascular invasion (MVI), hypercalcemia, anemia, thrombocytopenia and elevated C-reactive protein were significantly associated with OS. Multivariate analysis revealed that ECOG-PS (hazard ratio [HR] = 3.665, P = 0.0004), hypercalcemia (HR = 6.428, P = 0.0005) and the presence of MVI (HR = 2.668, P = 0.0109) were jointly significant poor prognostic factors. This is the first study analysing prognostic factors of mRCC patients with first-line IFN-α using large cohort of the prospective study. The present study suggests that first-line IFN-α is still a useful therapy for mRCC even in the era of molecular targeted therapy. PMID:27089226

  12. Combination of Calcitriol and Dietary Soy Exhibits Enhanced Anticancer Activity and Increased Hypercalcemic Toxicity in a Mouse Xenograft Model of Prostate Cancer

    PubMed Central

    Wang, Jennifer Y.; Swami, Srilatha; Krishnan, Aruna V.; Feldman, David

    2012-01-01

    Background The potential role of vitamin D and soy in prostate cancer (PCa) prevention/treatment has gained much attention in recent years. In this study, we evaluated the anticancer activity of calcitriol, the active form of vitamin D, dietary soy, and their combinations in a mouse model of PCa. Methods Athymic male nude mice bearing PC-3 human PCa xenografts received diets containing 10 kcal% or 20 kcal% soy, calcitriol injections, or a combination of dietary soy and calcitriol. Changes in tumor growth, serum levels of 1,25(OH)2D and calcium, and regulation of tumor gene expression were examined. Results The combination treatments resulted in substantially greater inhibition of tumor growth than either agent alone. Soy diets alone caused a modest elevation in serum 1,25(OH)2D, whereas the calcitriol-soy combinations led to substantially elevated serum 1,25(OH)2D, hypercalcemia, and in some cases lethal toxicity. The combinations enhanced calcitriol activity in regulating target gene expression, including greater up-regulation of anti-proliferative (p21, IGFBP-3) and pro-apoptotic (Bax) genes, increased inhibition of anti-apoptotic (Bcl-2) and cell cycle promoting (cyclin D1) genes, and suppression of prostaglandin (PG) synthesis and signaling (COX-2, 15-PGDH, PG receptors). Increases in serum calcium were accompanied by elevated expression of intestinal calcium absorption genes (TRPV6, calbindin-9k). Conclusions Soy increases the bioavailability of endogenous and administered calcitriol, thereby enhancing its anticancer effects and risk of hypercalcemia. Since both agents are easily available as dietary supplements, the increased potential for hypercalcemic toxicity becomes an important factor when considering the combined use of vitamin D and soy in PCa therapy. PMID:22457201

  13. [Clinical and biological forms of secondary hyperparathyroidism in dialysis patients].

    PubMed

    Jean, Guillaume; Souberbielle, Jean-Claude; Lorriaux, Christie; Mayor, Brice; Hurot, Jean-Marc; Deleaval, Patrick; Chazot, Charles

    2012-02-01

    The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well standardized in chronic renal failure patients. The aim of this study was to identify the main types of HPT on the basis of clinical and biological findings in a haemodialysis population. Between 2004 and 2010, all patients undergoing haemodialysis were observed and treated using the same strategy: conventional therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along with regular bone marker analysis. Wherever required, cinacalcet (CC) was administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158 were classified as having HPT (30%) with a serum PTH level greater than 300 pg/mL. From this population, we identified five main types of HPT: (1) HPT with 'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2) 'secondary' HPT had elevated bone marker levels, but showed favorable response to CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant' HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3, 1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We typified HPT on the basis of physiopathology and stages of HPT progression. Further studies on HPT that focus on bone marker levels are required to establish well-defined treatment strategies. In our study, HPT cases did not show uniform findings in Hémodialyse (HD) patients because of the variation in the stages of the disease at the time of diagnosis. PMID:21741337

  14. [Cervical macroadenoma causing hyperparathyroidism: Report of one case].

    PubMed

    Zapata P, Antonio; Delgado F, José; González V, Gilberto; Arteaga U, Eugenio

    2015-03-01

    We report a 59-year-old man with a history of hypertension, recurrent renal stones and a severe hypercalcemia of 14.9 mg/dl with a serum phosphorus of 2.4 mg/dl and a serum albumin of 3.6 g/dl. Physical examination showed a 4 cm left cervical nodule, consistent with the diagnosis of thyroid nodule. Parathyroid hormone (PTH) levels were 844 pg/mL (normal 15-65 pg/ml) and a cervical ultrasound examination disclosed a solid nodule in the lower left lobe of 40 x 30 x 25 mm, adjacent to the thyroid parenchyma. Abdominal ultrasound revealed bilateral renal stones. Parathyroid scintigraphy showed a high uptake of the left lower parathyroid mass and a bone densitometry showed bone density t scores of -1.2 in the spine, -2.0 in the right femoral neck and -3.5 in the distal radius. A review of his medical record revealed the presence of hypercalcemia for at least 4 years. He was admitted for hydration and administration of 4 mg zoledronic acid iv. At 24 hours, serum calcium dropped to 11.0 mg/dl, and a left thyroid lobectomy was performed including the lower left parathyroid gland. The pathology report showed a 22.6 g parathyroid adenoma. Intraoperatory PTH descended > 50%, consistent with successful parathyroidectomy. At 7 days after surgery serum calcium was 8.8 mg/dl, phosphorus 2.1 mg/dl, alkaline phosphatase 166 U/L, albumin 3.9 g/dL, PTH 230 pg/ml and 25-OH vitamin D 12.4 ng/ml. This finding was interpreted as secondary hyperparathyroidism due to vitamin D deficiency and "hungry bone", being less likely the presence of residual or metastatic parathyroid tissue. A cholecalciferol load was administered, with significant descent of PTH. PMID:26005829

  15. Vitamin D Signaling Modulators in Cancer Therapy.

    PubMed

    Luo, Wei; Johnson, Candace S; Trump, Donald L

    2016-01-01

    The antiproliferative and pro-apoptotic effects of 1α,25-dihydroxycholecalciferol (1,25(OH)2D3, 1,25D3, calcitriol) have been demonstrated in various tumor model systems in vitro and in vivo. However, limited antitumor effects of 1,25D3 have been observed in clinical trials. This may be attributed to a variety of factors including overexpression of the primary 1,25D3 degrading enzyme, CYP24A1, in tumors, which would lead to rapid local inactivation of 1,25D3. An alternative strategy for improving the antitumor activity of 1,25D3 involves the combination with a selective CYP24A1 inhibitor. The validity of this approach is supported by numerous preclinical investigations, which demonstrate that CYP24A1 inhibitors suppress 1,25D3 catabolism in tumor cells and increase the effects of 1,25D3 on gene expression and cell growth. Studies are now required to determine whether selective CYP24A1 inhibitors+1,25D3 can be used safely and effectively in patients. CYP24A1 inhibitors plus 1,25D3 can cause dose-limiting toxicity of vitamin D (hypercalcemia) in some patients. Dexamethasone significantly reduces 1,25D3-mediated hypercalcemia and enhances the antitumor activity of 1,25D3, increases VDR-ligand binding, and increases VDR protein expression. Efforts to dissect the mechanisms responsible for CYP24A1 overexpression and combinational effect of 1,25D3/dexamethasone in tumors are underway. Understanding the cross talk between vitamin D receptor (VDR) and glucocorticoid receptor (GR) signaling axes is of crucial importance to the design of new therapies that include 1,25D3 and dexamethasone. Insights gained from these studies are expected to yield novel strategies to improve the efficacy of 1,25D3 treatment. PMID:26827962

  16. Clodronate news of efficacy in osteoporosis

    PubMed Central

    Nardi, Alfredo; Ventura, Lorenzo; Cozzi, Luisella; Tonini, Greta

    2016-01-01

    Summary Clodronate belongs to Bisphosphonates family and it has been studied especially for osteoporosis treatment, Paget’s disease, osteolytic metastases, hypercalcemia malignancy and some childhood skeletal diseases. Besides the osteoporosis treatment, it has been successfully used for treating tumoral osteolysis and for bone localization of multiple myeloma, hypercalcemia malignancy, primary hyperparathyroidism, Paget’s disease and algodystrophy. Filipponi study showed a statistically significant reduction of the incidence of vertebral fractures after 4 years of treatment with clodronate, intravenously administered at a dose of 200 mg every three weeks. Frediani study, published in 2003 on BONE, proved the clodronate efficacy in the prevention of fractures caused by glucocorticoid-induced osteoporosis (GIO). Clodronate doses of 800 mg/day per os and 100 mg i.m./week are substantially equivalent, because the oral absorption is about 1,9%. A higher efficacy on BMD was documented in various works, especially in cohorts of patients with a greater fracture risk, using higher doses (1600 mg per os). This has led to the hypothesis of using clodronate 200 mg i.m. formulation. Clodronate is an osteoporosis drug that can be assumed in different doses (100 mg i.m./week, clodronate 200 mg i.m. every 2 weeks) considering the risk band, identified by algorithms (FRAX o DeFRA), by BMD and by the presence of at least one risk factor. That means that it is possible to envisage a differentiated use of clodronate adapting the doses to the fracture risk and to the severity of pain symptoms, thus promoting a greater adherence to the therapy. To conclude clodronate is helpful in reducing fracture risk, is safe, well tolerated, and has a good rate cost/effectiveness in patients with fracture risk over 7% established with FRAX. PMID:27252741

  17. 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.

  18. Deletions of the elastin gene in Williams Syndrome

    SciTech Connect

    Greenberg, F.; Nickerson, E.; McCaskill, C.

    1994-09-01

    To investigate deletions in the elastin gene in patients with Williams Syndrome (WS), we screened 37 patients and their parents for deletions in the elastin gene by both fluorescence in situ hybridization (FISH) using cosmid cELN272 containing the 5{prime} end of the elastin gene and by polymerase chain reaction (PCR) using a primer pair which amplifies intron 17 in the elastin gene, producing a polymorphic amplification product. Thirty-two patients have been investigated by both the FISH and PCR techniques, one patient was studied only by PCR, and 4 patients were studied only by FISH. Overall, 34 of 37 patients (92%) were deleted for the elastin gene. Using the PCR marker, 14 patients were informative and 12 were shown to be deleted [maternal (n=5) and paternal (n=7)]. Using cosmid cELN272, 33 of 36 patients demonstrated a deletion of chromosome 7q11.23. In one family, both the mother and daughter were deleted due to an apparently de novo deletion arising in the mother. Three patients were not deleted using the elastin cosmid; 2 of these patients have classic WS. Another non-deleted patient has the typical facial features and hypercalcemia but normal intelligence. These three patients will be important in delineating the critical region(s) responsible for the facial features, hypercalcemia, mental retardation and supravalvular aortic stenosis (SVAS). There was not an absolute correlation between deletions in elastin and SVAS, although these individuals may be at risk for other cardiovascular complications such as hypertention. Since the majority of WS patients are deleted for a portion of the elastin gene, most likely this marker will be an important diagnostic tool, although more patients will need to be studied. Those patients who are not deleted but clinically have WS will be missed using only this one marker. Expansion of the critical region to other loci and identification of additional markers will be essential for identifying all patients with WS.

  19. Concurrent activation of granulocytes and osteoclasts in busulfan-suppressed bone marrow in response to transplantation of a mammary carcinoma in mice.

    PubMed

    McCracken, C H; Lottsfeldt, J L; Lee, M Y

    1988-05-01

    Transplantation of CE mammary adenocarcinoma (CE maca) into normal mice produces both neutrophilia and hypercalcemia due to osteoclastic bone resorption. In order to explore the physiology of osteoclast formation in vivo, the time course of neutrophilia and osteoclast development was examined in mice that had been pretreated with busulfan prior to the CE maca implantation. Busulfan-treated tumor-bearing mice (BUTUM), busulfan-treated control mice (BUCON), tumor-bearing mice with no busulfan (TUM), and normal controls (CON) were sacrificed on days 4, 7, 11, 14, and 17 after tumor implantation. Leukocyte counts, serum calcium levels, marrow cellularity, and marrow colony-forming units (CFU) were determined. Osteoclasts were quantified histologically by the osteoclast: endosteum ratio (OER). BUCON bone marrow was hypoplastic with CFU remaining significantly lower than that of controls over the course of the experiment. In contrast, BUTUM marrow CFU increased dramatically with the growth of the tumor. The most predominant increase was observed in neutrophilic CFU. Development of hypercalcemia closely paralleled neutrophilia in both TUM and BUTUM mice, although these changes were significantly delayed in the BUTUM group. The neutrophil count and serum calcium levels remained within normal control levels for BUCON mice. The OER correlated with serum calcium, and it closely paralleled the neutrophil count in TUM and BUTUM mice. These results clearly indicated the stimulation of bone marrow neutrophilic granulocyte progenitors and osteoclasts by the CE maca, indicating that the bone marrow is the primary target of this tumor. There may be a closely related mechanism in osteoclast and granulocyte stimulation by one or more CE maca factors. PMID:3360066

  20. Carboxyl-terminal fragments of parathyroid hormone are not secreted preferentially in primary hyperparathyroidism as they are in other hypercalcemic conditions.

    PubMed

    Brossard, J H; Whittom, S; Lepage, R; D'Amour, P

    1993-08-01

    Calcium infusion in normal men decreases immunoreactive PTH (iPTH). Intact iPTH (I) shows the greatest decline, and there is a greater decrease in carboxyl-terminal iPTH (C) than in midcarboxyl-terminal iPTH (M); thus, C/I, M/I, and M/C ratios are increased. To verify whether this adaptive mechanism to hypercalcemia was present in patients with primary hyperparathyroidism (PHP), we measured total serum calcium (Ca), I, C, and M as well as C/I, M/I, and M/C ratios in 32 normocalcemic normal subjects (NN), in the same normal subjects made hypercalcemic (HN), in 31 patients with PHP, and in 12 patients with nonparathyroid hypercalcemia (NPHN). Eight patients with PHP and the 32 NN were submitted to CaCl2 and Na2 EDTA infusions to evaluate their parathyroid function. Ca was lower (P < 0.005) in NN (2.21 +/- 0.06 mmol/L) than in PHP (2.80 +/- 0.25 mmol/L) or NPHN (2.83 +/- 0.20 mmol/L). The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects. C, M, and I were increased in PHP compared to the other groups (P < 0.005). PHP had C/I and M/I ratios of 2.03 +/- 0.72 and 9.04 +/- 7.69, values similar to NN (2.29 +/- 0.55 and 8.70 +/- 3.0), but lower than HN (5.36 +/- 2.48 and 25.93 +/- 13.86; P < 0.005) and NPHN (11.91 +/- 13.06 and 18.69 +/- 10.81; P < 0.005). NPHN also had a lower M/C ratio than HN (2.76 +/- 2.02 vs. 4.99 +/- 1.81; P < 0.05). PHP and NN could increase their C/I ratio to the same maximum (4.71 +/- 1.26 vs. 5.70 +/- 2.94), but PHP did so at a much higher set-point (2.67 +/- 0.19 vs. 2.24 +/- 0.10 mmol/L; P < 0.005). PHP also had higher set-points for M/I, and M/C ratios even if they failed to increase the ratios to the high values in NN [M/I 11.6 +/- 6.4 vs. 29.3 +/- 18.3 (P < 0.005); M/C, 2.16 +/- 1.20 vs. 5.0 +/- 1.93 (P < 0.005)]. Thus, carboxyl-terminal fragments are not secreted preferentially in PHP as they are in other hypercalcemic conditions. This relates to a higher set-point for the regulation of C/I and M/I ratios

  1. Vitamin D toxicity redefined: vitamin K and the molecular mechanism.

    PubMed

    Masterjohn, Christopher

    2007-01-01

    The dose of vitamin D that some researchers recommend as optimally therapeutic exceeds that officially recognized as safe by a factor of two; it is therefore important to determine the precise mechanism by which excessive doses of vitamin D exert toxicity so that physicians and other health care practitioners may understand how to use optimally therapeutic doses of this vitamin without the risk of adverse effects. Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption, soft tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed. The hypothesis presented in this paper proposes the novel understanding that vitamin D exerts toxicity by inducing a deficiency of vitamin K. According to this model, vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D. This hypothesis is circumstantially supported by the observation that animals deficient in vitamin K or vitamin K-dependent proteins exhibit remarkable similarities to animals fed toxic doses of vitamin D, and the observation that vitamin D and the vitamin K-inhibitor Warfarin have similar toxicity profiles and exert toxicity synergistically when combined. The hypothesis further proposes that vitamin A protects against the toxicity of vitamin D by decreasing the expression of vitamin K-dependent proteins and thereby

  2. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study

    PubMed Central

    2011-01-01

    Introduction Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period. Methods This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube. Results The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only. Conclusions This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients. EudraCT Number 2009-012080-34 German Clinical Trials Register (DRKS) DRKS

  3. The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

    NASA Technical Reports Server (NTRS)

    Dobnig, H.; Turner, R. T.

    1997-01-01

    PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible

  4. Calciphylaxis in end-stage renal disease prior to dialytic treatment: a case report and literature review

    PubMed Central

    Tamayo-Isla, Ramón Alberto; Cuba de la Cruz, Mauro

    2015-01-01

    Introduction Calciphylaxis is a rare medical condition that is usually diagnosed in patients suffering from end-stage renal disease who are already receiving renal replacement therapy and in those post-transplantation. The pathogenesis still remains to be fully elucidated; hence, the treatment is not uniform. The prognosis is generally poor. The ulcerative stage exhibits a worse prognosis than the nonulcerative one. Calciphylaxis presenting in terminal kidney disease prior to dialytic treatment has only rarely been reported. Case presentation A 32-year-old female Caucasian clerk sought medical attention for increasing tiredness and lower limb skin ulcers. Polycystic kidney disease was diagnosed in her late father and two of her siblings. At the first nephrology consultation, obesity, pallor, bilateral flank masses with ballottement, and two ulcers with a dark necrotic center on the distal left leg were noted. In addition, another indurated light bluish lesion of 5 cm just above the right knee with intact skin was observed. All lesions were very tender and warm on touch. Laboratory results yielded hypercalcemia, hyperphosphatemia, anemia, and parathyroid hormone levels that were more than ten times the normal values in the patient, and with a glomerular filtration rate of 4 mL/minute. Skin biopsy confirmed the suspicion of calciphylaxis. The patient was placed on peritoneal dialysis with low Ca concentration baths, cinacalcet, and aluminum hydroxide. The results included correction of hypercalcemia, improvement of phosphate levels, and the product of both Ca and phosphate, but only a transitory decrease in serum parathyroid hormone levels. The ulcerations were completely healed after 2 months of treatment. Cinacalcet was discontinued after 18 months, but multiple large-size, nonulcerative indurated areas appeared 3 months later in the lower limbs after discontinuation of the drug. A parathyroidectomy performed 17 months later revealed a four-gland hyperplastic

  5. Case Report on Renal Failure Reversal in Lambda Chain Multiple Myeloma with Bortezomib and Dexamethasone

    PubMed Central

    Patibandla, Bhanu K.; Alwassia, Ahmad A.; Bartley, Anthony; Sandhu, Gurprataap S.; Rooney, James; Black, Robert M.

    2014-01-01

    Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count—18,900/μL with no bandemia, hemoglobin 10.8 gm/dL, potassium—6.7 mEq/L, bicarbonate—15 mEq/L, blood urea nitrogen—62 mg/dL, SCr—5.6 mg/dL (baseline: 1.10), and corrected calcium—11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen. PMID:25045553

  6. 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

  7. Na+ and Ca2+ ingestion - Plasma volume-electrolyte distribution at rest and exercise

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Brock, P. J.

    1980-01-01

    The effects of hypernatremia and hypercalcemia on plasma volume and electrolyte distribution during rest, exercise and recovery in cool and hot environments are investigated. Plasma volume, protein and electrolytes were measured in two groups of five men in the supine position during rest, exercise at 40-47% maximal oxygen consumption and recovery in 26.5 C and 39.4 C environments, after ingestion in the rest period of 16-17 ml/kg hypertonic NaCl, isotonic NaCl or hypertonic calcium gluconate solutions. During the rest period, it is found that the hypertonic Ca drink prevents any rise in plasma volume in both cool and hot environments, while hypertonic Na retarded hypervolemia only in the cool environment and consumption of both isotonic and hypertonic Na in the heat resulted in a hypervolemic response twice as great as that in the cool environment. During exercise and recovery, plasma volume is found to be greatest after drinking hypertonic Na in the heat, while the normal hypervolemic responses during exercise were not influenced by drink composition. Results suggest that hypertonic drinks may be better for maintaining plasma volumes during exercise in the heat.

  8. Obstructive Jaundice as Initial Presentation of Multiple Myeloma: Case Presentation and Literature Review

    PubMed Central

    Khan, Yasir; Mansour, Iyad; Ong, Eric; Shrestha, Manish

    2015-01-01

    Multiple myeloma is a malignant plasma-cell disorder that primarily involves the bone marrow, but extramedullary involvement is becoming increasingly common (Bladé et al., 2012) both at initial presentation and follow-up. Most common initial presentations for multiple myeloma include generalized fatigue, renal insufficiency, bone pain, and recurrent bacterial infections. We present a case of a healthy 55-year-old man that presented to the emergency department with a three-week history of anorexia and jaundice without any past medical history. Patient's initial labs were significant for hyperbilirubinemia and elevated liver function enzymes (AST, ALT, ALP, and GGT). Additional laboratory workup was significant for mild hypercalcemia and increased protein gap. MRI and ERCP suggested primary sclerosing cholangitis but were not diagnostic. Liver biopsy illustrated plasma-cell infiltration and bone marrow biopsy diagnosed multiple myeloma with extramedullary disease. Patient was started on dexamethasone, bortezomib, and cyclophosphamide, but, despite this aggressive regimen, the patient continued to decline. We take this opportunity to present this atypical presentation of a common hematological malignancy and review the associated literature. PMID:26221143

  9. The emerging role of genomics in the diagnosis and workup of congenital urinary tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1

    PubMed Central

    Materna-Kiryluk, Anna; Kiryluk, Krzysztof; Burgess, Katelyn E; Bieleninik, Arkadiusz; Sanna-Cherchi, Simone; Gharavi, Ali G.; Latos-Bielenska, Anna

    2014-01-01

    Background Copy number variants (CNVs) are increasingly recognized as an important cause of congenital malformations and likely explain over 16% cases of CAKUT. Here, we illustrate how a molecular diagnosis of CNV can inform the clinical management of a pediatric patient presenting with CAKUT and other organ defects. Methods We describe a 14 year-old girl with a large de novo deletion of chromosome 3q13.31-22.1 that disrupts 101 known genes and manifests with CAKUT, neurodevelopmental delay, agenesis of corpus callosum (ACC), cardiac malformations, electrolyte and endocrine disorders, skeletal abnormalities and dysmorphic features. We perform extensive annotation of the deleted region to prioritize genes for specific phenotypes and to predict future disease risk. Results Our case defined new minimal chromosomal candidate regions for both CAKUT and ACC. Moreover, the presence of the CASR gene in the deleted interval predicted a diagnosis of hypocalciuric hypercalcemia, which was confirmed by serum and urine chemistries. Our gene annotation explained clinical hypothyroidism and predicted that the index case is at increased risk of thoracic aortic aneurysm, renal cell carcinoma and myeloproliferative disorder. Conclusions Extended annotation of CNV regions refines diagnosis and uncovers previously unrecognized phenotypic features. This approach enables personalized treatment and prevention strategies in patients harboring genomic deletions. PMID:24292865

  10. Potential applications of biphosphonates in dental surgical implants.

    PubMed

    Berardi, D; Carlesi, T; Rossi, F; Calderini, M; Volpi, R; Perfetti, G

    2007-01-01

    Biphosphonates are largely used for their unquestionable properties of inhibiting bone resorption by osteoclasts in the treatment of various osteometabolic illnesses such as osteoporosis, multiple myeloma, tumors which metastasize to the bone and malignant hypercalcemia. In this literature review the physico-chemical properties, biologic activities and the mechanisms of action of biphosphonates are described. The use of these drugs is discussed, analyzing the quantity of results which have emerged through in vitro and in vivo experiments on animal models. In this study the efficiency of these drugs is demonstrated in contrasting the osteolitic processes of the alveolar bone, in promoting the neoformation and in bettering the quality of bone implants. However, it is important to draw attention to a worrying correlation which has emerged during the last 3-4 years, between osteonecrosis of the jaw (ONJ) and the systemic administration of aminobiphosphonates. This collateral effect did not emerge following the use of non-aminobiphosphonates. The aim of this review is to identify the guidelines for the use of biphosphonates in oral implant surgery. PMID:17880759

  11. Unusual case of calciphylaxis associated with metastatic breast carcinoma.

    PubMed

    Bosler, David S; Amin, Mitual B; Gulli, Farris; Malhotra, Rajwant K

    2007-08-01

    Calciphylaxis is a relatively rare disorder associated with calcification of small- and medium-sized blood vessels, progressive ischemic skin necrosis, and ulcerations. It is usually seen in patients with end-stage renal disease with secondary hyperparathyroidism and is occasionally seen in primary hyperparathyroidism, hypercalcemia of malignancy, and end-stage liver disease. We report an unusual case of calciphylaxis seen in association with metastatic breast carcinoma in the absence of end-stage renal or parathyroid disease. A 73-year-old woman presented with painful leg ulcers. Serum calcium levels and parathormone levels were within normal limits. Skin biopsies from the ulcers revealed small- to medium-sized subcutaneous arteries with calcification of the media. Some of the arteries were narrowed by fibrointimal hyperplasia and fibrin thrombi. Calcification of the subcutaneous fat, fat necrosis, and suppuration were also seen. Calciphylaxis associated with metastatic osteolytic breast carcinoma is rare. Although end stage renal disease with secondary hyperparathyroidism is the most common cause of calciphylaxis, this case demonstrates that less common conditions with normal serum calcium and parathormone levels may also cause it. PMID:17667177

  12. Indices of adrenal deficiency involved in brain plasticity and functional control reorganization in hemodialysis patients with polysulfone membrane: BOLD-fMRI study.

    PubMed

    Belaïch, Rachida; Boujraf, Saïd; Benzagmout, Mohammed; Maaroufi, Mustapha; Housni, Abdelkhalek; Batta, Fatima; Tizniti, Siham; Magoul, Rabia; Sqalli, Tarik

    2016-06-01

    This work purpose was to estimate the implication of suspected adrenal function deficiencies, which was influenced by oxidative stress (OS) that are generating brain plasticity, and reorganization of the functional control. This phenomenon was revealed in two-hemodialysis patients described in this paper. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) revealed a significant activation of the motor cortex. Hemodialysis seems to originate an inflammatory state of the cerebral tissue reflected by increased OS, while expected to decrease since hemodialysis eliminates free radicals responsible for OS. Considering adrenal function deficiencies, sensitivity to OS and assessed hyponatremia and hypercalcemia, adrenal function deficiencies is strongly suspected in both patients. This probably contributes to amplify brain plasticity and a reorganization of functional control after hemodialysis that is compared to earlier reported studies. Brain plasticity and functional control reorganization was revealed by BOLD-fMRI with a remarkable sensitivity. Brain plastic changes are originated by elevated OS associating indices of adrenal function deficiencies. These results raise important issues about adrenal functional deficiencies impact on brain plasticity in chronic hemodialysis-patients. This motivates more global studies of plasticity induced factors in this category of patients including adrenal functional deficiencies and OS. PMID:27301905

  13. Myeloma bone disease: Pathophysiology and management

    PubMed Central

    Silbermann, Rebecca; Roodman, G. David

    2013-01-01

    Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases tumor growth, directly stimulates the OCL formation, and induces cells in the marrow microenvironment to produce factors that drive OCL formation and suppress OBL formation. Factors produced by marrow stromal cells and OCL promote tumor growth through direct action on myeloma cells and by increasing angiogenesis. Current therapies targeting MMBD focus on preventing osteoclastic bone destruction; however regulators of OBL inhibition in MMBD have also been identified, and targeted agents with a potential anabolic effect in MMBD are under investigation. This review will discuss the mechanisms responsible for MMBD and therapeutic approaches currently in use and in development for the management of MMBD. PMID:26909272

  14. Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma

    PubMed Central

    Rajkumar, S. Vincent

    2014-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a serum monoclonal (M) protein level less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of hypercalcemia, renal insufficiency, anemia, or bone lesions attributable to a clonal plasma cell disorder. Patients may be tested for a monoclonal gammopathy by serum protein electrophoresis, immunofixation, and the free light chain (FLC) assay. The prevalence of MGUS is 3% for persons more than 50 years of age and 5% in those more than 70 years of age. The risk of progression to multiple myeloma or a related disorder is 1% per year. The size and type of M protein, the number of bone marrow plasma cells, and the results of the FLC ratio are independent risk factors for progression. Smoldering multiple myeloma (SMM) is a more advanced premalignant phase than MGUS and is characterized by more than 3 g/dL of serum M protein, more than 10% clonal plasma cells in the bone marrow, or both, with no evidence of end-organ damage. PMID:20425398

  15. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    PubMed Central

    Cannonier, Shellese A.; Sterling, Julie A.

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

  16. 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

  17. 14-3-3 Proteins Buffer Intracellular Calcium Sensing Receptors to Constrain Signaling

    PubMed Central

    Grant, Michael P.; Cavanaugh, Alice; Breitwieser, Gerda E.

    2015-01-01

    Calcium sensing receptors (CaSR) interact with 14-3-3 binding proteins at a carboxyl terminal arginine-rich motif. Mutations identified in patients with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia, pancreatitis or idiopathic epilepsy support the functional importance of this motif. We combined total internal reflection fluorescence microscopy and biochemical approaches to determine the mechanism of 14-3-3 protein regulation of CaSR signaling. Loss of 14-3-3 binding caused increased basal CaSR signaling and plasma membrane levels, and a significantly larger signaling-evoked increase in plasma membrane receptors. Block of core glycosylation with tunicamycin demonstrated that changes in plasma membrane CaSR levels were due to differences in exocytic rate. Western blotting to quantify time-dependent changes in maturation of expressed wt CaSR and a 14-3-3 protein binding-defective mutant demonstrated that signaling increases synthesis to maintain constant levels of the immaturely and maturely glycosylated forms. CaSR thus operates by a feed-forward mechanism, whereby signaling not only induces anterograde trafficking of nascent receptors but also increases biosynthesis to maintain steady state levels of net cellular CaSR. Overall, these studies suggest that 14-3-3 binding at the carboxyl terminus provides an important buffering mechanism to increase the intracellular pool of CaSR available for signaling-evoked trafficking, but attenuates trafficking to control the dynamic range of responses to extracellular calcium. PMID:26317416

  18. Genetic aspects of pancreatitis.

    PubMed

    Whitcomb, David C

    2010-01-01

    Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene x gene and gene x environmental interactions. PMID:20059346

  19. A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye

    PubMed Central

    Varım, Ceyhun; Ergenc, Hasan; Uyanık, Mehmet Sevki; Kaya, Tezcan; Nalbant, Ahmet; Karacaer, Cengiz; Sunu, Cenk; Tamer, Ali

    2015-01-01

    Multiple myeloma (MM), the second most common hematological malignancy, is caused by the accumulation of monoclonal plasma cells in bone marrow. It accounts for 10–15% of deaths from hematological malignancies and approximately 2% of deaths from cancer. The median age at presentation is 70 years old. The diagnosis is incidental in 30% of cases. MM is often discovered through routine blood screening with a large gap between the total protein and the albumin levels. Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye). Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR) to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma. PMID:27275266

  20. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

    PubMed Central

    Borazanci, Erkut; Millis, Sherri Z; Korn, Ron; Han, Haiyong; Whatcott, Clifford J; Gatalica, Zoran; Barrett, Michael T; Cridebring, Derek; Von Hoff, Daniel D

    2015-01-01

    Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient’s tumor. Further work should be pursued to better characterize this disease. PMID:26380056

  1. Bisphosphonate-Related Osteonecrosis of the Jaw: Historical, Ethical, and Legal Issues Associated With Prescribing

    PubMed Central

    Faiman, Beth; Pillai, Aiswarya Lekshmi Pillai Chandran; Benghiac, Ana Gabriela

    2013-01-01

    The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration. PMID:25031978

  2. 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.

  3. 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.

  4. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report

    PubMed Central

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-01-01

    Abstract. We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2–13.8 mg/dL), elevated levels of intact PTH (86–160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband’s mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband’s elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  5. Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

    PubMed

    Leibrock, Christina B; Voelkl, Jakob; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Kuro-O, Makoto; Lang, Florian

    2016-01-01

    Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. PMID:26538435

  6. Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer.

    PubMed

    Irelli, Azzurra; Cocciolone, Valentina; Cannita, Katia; Zugaro, Luigi; Di Staso, Mario; Lanfiuti Baldi, Paola; Paradisi, Stefania; Sidoni, Tina; Ricevuto, Enrico; Ficorella, Corrado

    2016-06-01

    Cancer cells can alter physiological mechanisms within bone resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted therapy, as bisphosphonates and denosumab, are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. The toxicity profile is similar between bisphosphonates and denosumab, even if pyrexia, bone pain, arthralgia, renal failure and hypercalcemia are more common with bisphosphonates, while hypocalcemia and toothache are more frequently reported with denosumab. Osteonecrosis of the jaw (ONJ) occurred infrequently without statistically significant difference. The present review aims to provide an assessment on bone targeted therapies for preventing the occurrence of SREs in bone metastatic breast cancer patients, critically analyzing the evidence available so far on their effectiveness, in light of the different mechanisms of action. Thus, we try to provide tools for the most fitting treatment of bone metastatic breast cancer patients. We also provide an overview on the usefulness of bone turnover markers in clinical practice and new molecules currently under study for the treatment of bone metastatic disease. PMID:27091227

  7. The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

    PubMed Central

    Brennan, Sarah C.; Wilkinson, William J.; Tseng, Hsiu-Er; Finney, Brenda; Monk, Bethan; Dibble, Holly; Quilliam, Samantha; Warburton, David; Galietta, Luis J.; Kemp, Paul J.; Riccardi, Daniela

    2016-01-01

    Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases. PMID:26911344

  8. Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

    PubMed Central

    Pacini, Stefania; Morucci, Gabriele; Branca, Jacopo J. V.; Aterini, Stefano; Amato, Marcello; Gulisano, Massimo; Ruggiero, Marco

    2013-01-01

    Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification. PMID:23749205

  9. Effect of Androctonus bicolor scorpion venom on serum electrolytes in rats: A 24-h time-course study.

    PubMed

    Al-Asmari, A; Khan, H A; Manthiri, R A

    2016-03-01

    Black fat-tailed scorpion (Androctonus bicolor) belongs to the family Buthidae and is one of the most venomous scorpions in the world. The effects of A. bicolor venom on serum electrolytes were not known and therefore investigated in this study. Adult male Wistar rats were randomly divided into seven groups with five animals in each group. One of the groups served as control and received vehicle only. The animals in the remaining groups received a single subcutaneous injection of crude A. bicolor venom (200 μg/kg bodyweight) and were killed at different time intervals including 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after venom injection. The results showed that scorpion venom caused significant increase in serum sodium levels within 30 min after injection which slightly subsided after 1 h and then persisted over 24 h. Serum potassium levels continued to significantly increase until 4 h and then slightly subsided. There were significant decreases in serum magnesium (Mg(+)) levels following scorpion venom injection, at all the time points during the course of study. Serum calcium levels were significantly increased during the entire course of study, whereas serum chloride was significantly decreased. In conclusion, A. bicolor envenomation in rats caused severe and persistent hypomagnesemia with accompanied hypernatremia, hyperkalemia, and hypercalcemia. It is important to measure serum Mg(+) levels in victims of scorpion envenomation, and patients with severe Mg(+) deficiency should be treated accordingly. PMID:25964378

  10. Exogenous lipoid pneumonia. Clinical and radiological manifestations.

    PubMed

    Marchiori, Edson; Zanetti, Gláucia; Mano, Claudia Mauro; Hochhegger, Bruno

    2011-05-01

    Lipoid pneumonia results from the pulmonary accumulation of endogenous or exogenous lipids. Host tissue reactions to the inhaled substances differ according to their chemical characteristics. Symptoms can vary significantly among individuals, ranging from asymptomatic to severe, life-threatening disease. Acute, sometimes fatal, cases can occur, but the disease is usually indolent. Possible complications include superinfection by nontuberculous mycobacteria, pulmonary fibrosis, respiratory insufficiency, cor pulmonale, and hypercalcemia. The radiological findings are nonspecific, and the disease presents with variable patterns and distribution. For this reason, lipoid pneumonia may mimic many other diseases. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil, characteristic radiological findings, and the presence of lipid-laden macrophages on sputum or BAL analysis. High-resolution computed tomography (HRCT) is the best imaging modality for the diagnosis of lipoid pneumonia. The most characteristic CT finding in LP is the presence of negative attenuation values within areas of consolidation. There are currently no studies in the literature that define the best therapeutic option. However, there is a consensus that the key measure is identifying and discontinuing exposure to the offending agent. Treatment in patients without clinical symptoms remains controversial, but in patients with diffuse pulmonary damage, aggressive therapies have been reported. They include whole lung lavage, systemic corticosteroids, and thoracoscopy with surgical debridement. PMID:21185165

  11. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    DOE PAGESBeta

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; Hu, Zebin; Cleveland, Elyse; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart R.; Shevrin, Daniel; et al

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle tomore » establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.« less

  12. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    SciTech Connect

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; Hu, Zebin; Cleveland, Elyse; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart R.; Shevrin, Daniel; Kaul, Karen; Brendler, Charles; Iozzo, Renato V.; Seth, Prem

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle to establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.

  13. [Is denosmab really effective and safe in the care of CKD-MBD?].

    PubMed

    Hamano, Takayuki; Nakano, Chikako

    2016-09-01

    The authors of Freedom study enrolling primary osteoporosis patients argued that the anti-fracture effect of denosmab is not dependent on baseline estimated glomerular filtration rate(eGFR)by showing the non-significant interaction term between treatment and CKD stage. However, given disproportionate numbers of patients in each subgroup(4069, 2817, and only 73 patients, in CKD stage 2, 3, and, 4, respectively), this study seems to lack the statistical power to reach a definite conclusion on the effect modification by CKD stage. Truly, the serum concentration of infused denosmab in patients with CKD stage 4 is equivalent to that in patients without CKD, the risk of developing life-threatening or prolonged hypocalcemia is huge even under active vitamin D therapy in this population. In hemodialysis patients, this drug is relatively safer because each dialysis session delivers calcium into the circulation 3 times a week. However, even with concomitant administration of massive active vitamin D, the increase of intact PTH levels greater than 1000 pg/mL by this agent is not rare. In other words, this drug worsens secondary hyperparathyroidism. Moreover, reportedly, calcium and active vitamin D administered to avoid hypocalcemia can lead to ectopic calcification especially under the low bone turnover induced by this agent. In fact, transient hypercalcemia often follows hypocalcemia by the inevitable calcium supplementation. PMID:27561346

  14. [Vitamin D as an important steroid hormone in breast cancer].

    PubMed

    Obermannova, R; Demlová, R; Drábová, K; Melichárková, K; Greplová, K; Mrkvicová, M; Zdražilová-Dubská, L; Vyzula, R; Valík, D

    2014-01-01

    Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer. PMID:24945552

  15. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    PubMed Central

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

  16. 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

  17. 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

  18. The role of bisphosphonates in the management of advanced cancer with a focus on non-small-cell lung cancer. Part 1: Mechanisms of action, role of biomarkers and preclinical applications.

    PubMed

    Saba, Nabil; Khuri, Fadlo

    2005-01-01

    With recent advances in cancer management, patients with metastatic bone disease are likely to have a prolonged clinical course, with skeletal-related events such as pain, hypercalcemia, pathologic fractures, spinal cord and nerve compression. Bisphosphonate use has resulted in the reduction of skeletal-related complications for a number of tumors including breast, prostate and myeloma, and improvements in the quality of life for patients. There is now evidence that newer, highly potent, nitrogen-containing bisphosphonates reduce skeletal complications in patients with bone metastases from other solid tumors (including lung cancer). The early identification of patients at high risk for developing bone metastases may help curtail a complex and costly clinical problem--skeletal-related events. In this article, we review the different mechanisms of bisphosphonates and the potential role of newer-generation bisphosphonates, such as zoledronic acid, in the management of advanced, metastatic bone disease. We include a review of mechanistic studies and preclinical data. Additionally, the utility of evolving concepts such as bone markers and imaging of bone metastases are discussed. PMID:15775688

  19. Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease.

    PubMed

    Maritsi, Despoina N; Zarganis, Diagoras; Metaxa, Zoi; Papaioannou, Georgia; Vartzelis, George

    2013-01-01

    We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent. PMID:23424700

  20. How I treat plasma cell leukemia

    PubMed Central

    Lokhorst, Henk M.; Anderson, Kenneth C.; Richardson, Paul G.

    2012-01-01

    Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum β2-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients. PMID:22837533

  1. Differentiation Therapy of Acute Myeloid Leukemia

    PubMed Central

    Gocek, Elzbieta; Marcinkowska, Ewa

    2011-01-01

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML. PMID:24212816

  2. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    PubMed Central

    Mussap, Michele; Merlini, Giampaolo

    2014-01-01

    The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

  3. Multiple Myeloma and Kidney Disease

    PubMed Central

    Noiri, Eisei

    2013-01-01

    Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis. PMID:24288486

  4. Mineral Metabolism in European Children Living with a Renal Transplant: A European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry Study

    PubMed Central

    Bonthuis, Marjolein; Busutti, Marco; Jager, Kitty J.; Baiko, Sergey; Bakkaloğlu, Sevcan; Battelino, Nina; Gaydarova, Maria; Gianoglio, Bruno; Parvex, Paloma; Gomes, Clara; Heaf, James G.; Podracka, Ludmila; Kuzmanovska, Dafina; Molchanova, Maria S.; Pankratenko, Tatiana E.; Papachristou, Fotios; Reusz, György; Sanahuja, Maria José; Shroff, Rukshana; Groothoff, Jaap W.; Schaefer, Franz; Verrina, Enrico

    2015-01-01

    Background and objectives Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. Design, setting, participants, & measurements This study included 1237 children (0–17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. Results Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. Conclusions Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction. PMID:25710805

  5. Recent advances in multiple myeloma: a Korean perspective.

    PubMed

    Hong, Junshik; Lee, Jae Hoon

    2016-09-01

    Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration's approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea's trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea. PMID:27604794

  6. Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: Usefulness of /sup 99m/Tc-pyrophosphate bone scintigraphy

    SciTech Connect

    Kinnaert, P.; Van Hooff, I.; Schoutens, A.; Bergmann, P.; Fuss, M.; Dratwa, M.; Vienne, A.; Pasteels, J.L.; van Geertruyden, J.; Vanherweghem, J.L.

    1989-03-01

    Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D3 sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1 +/- 0.3) was significantly higher than in all other categories (5.9 +/- 0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients, p less than 0.01). Patients with massive aluminum accumulation in bone (greater than 75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism. /sup 99m/Tc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.

  7. 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

  8. Teriparatide is safe and effectively increases bone biomarkers in institutionalized individuals with osteoporosis.

    PubMed

    Ryder, Kathryn M; Tanner, S Bobo; Carbone, Laura; Williams, John E; Taylor, Henry M; Bush, Andrew; Pintea, Victorina; Watsky, Mitchell A

    2010-03-01

    Institutionalized adults with severe developmental disabilities have a high rate of minimal trauma and appendicular fracture. There is little information about osteoporosis treatment in this population. In this efficacy and safety study, men and women with severe developmental disabilities and osteoporosis received 20 mcg teriparatide subcutaneously daily for 18-24 months. Markers of bone formation [procollagen type 1 intact N-terminal propeptide (P1NP)] and resorption [C-telopeptide (CTx)] were measured at three-month intervals. Serum calcium was measured at two-week intervals for 12 weeks and thereafter at three-month intervals. Twenty-seven individuals received at least one injection. The incidence of hypercalcemia was 11.1% but was persistent and led to medication discontinuation in only one participant. Biomarkers of bone formation increased rapidly, doubling by three months. At 12 months, P1NP and CTx remained elevated from baseline; P1NP had risen from 66.95 +/- 83.71 microg/l (mean +/- SD) to 142.42 +/- 113.85 microg/l (P = 0.05), and CTx had increased from 0.377 +/- 0.253 to 1.016 +/- 1.048 ng/ml (P = 0.01). The majority of participants had an increase in P1NP of over 10 microg/l. In conclusion, teriparatide is safe and effective in developmentally disabled institutionalized adults. Serial calcium measurements are warranted, particularly during the first three months of therapy. PMID:19806302

  9. Bone and hormonal changes induced by skeletal unloading in the mature male rat

    NASA Technical Reports Server (NTRS)

    Dehority, W.; Halloran, B. P.; Bikle, D. D.; Curren, T.; Kostenuik, P. J.; Wronski, T. J.; Shen, Y.; Rabkin, B.; Bouraoui, A.; Morey-Holton, E.

    1999-01-01

    To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

  10. A nontoxic case of vitamin D toxicity.

    PubMed

    Chakraborty, Sutirtha; Sarkar, Ajoy Krishna; Bhattacharya, Chandramouli; Krishnan, Prasad; Chakraborty, Subhosmito

    2015-01-01

    Vitamin D toxicity also known as hypervitaminosis D was previously believed to be rare. But with an increase in vitamin D supplementation several cases have been reported in literature. Fat soluble vitamins like Vitamin D, due to their ability to accumulate in the body, have a higher potential for toxicity than water soluble vitamins. The main clinical consequence of vitamin D toxicity is hypercalcemia. In this report we describe an adult female patient who developed very high serum Vitamin D levels (746 ng/mL, RI: 20 to 50) as a result of medication error. Inspite of such high serum concentrations the patient was without any clinical symptoms and had normal serum calcium. We critically discuss the mechanism of toxicity and hypothesize the possible molecular/metabolic factors which might have been responsible for this nontoxic presentation. This case study highlights the fact that physicians need to consider the risk of medication errors while prescribing Vitamin D therapy. Clinical trials to study Vitamin D toxicity in humans is not possible ethically. Thus the evidence base regarding the safety profile of Vitamin D supplementation in humans has been build through case reports. This review of the paradoxical clinico-laboratory manifestation of hypervitaminosis D could possibly contribute to existing literature. PMID:25918194

  11. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy

    PubMed Central

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent’s use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere®) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 μg) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  12. Calcitriol in the treatment of prostate cancer.

    PubMed

    Beer, Tomasz M; Myrthue, Anne

    2006-01-01

    Calcitriol, the principal active metabolite of vitamin D and a naturally occurring hormone, showed significant antineoplastic activity in pre-clinical models of prostate cancer and many other tumor types. These antineoplastic effects were observed at calcitriol concentrations substantially above the physiological range. While a number of mechanisms of action have been postulated, the induction of apoptosis and inhibition of proliferation have been most extensively reported. These pre-clinical findings motivated several investigators to pursue a series of clinical trials to examine the potential of targeting the vitamin D receptor for cancer treatment using calcitriol. Initial studies tested daily dosing of calcitriol and showed that substantial dose escalation was not feasible due to hypercalciuria and/or hypercalcemia. In contrast, weekly dosing of calcitriol allowed substantial dose escalation without dose-limiting toxicities. Notably, however, the commercially available formulation of calcitriol exhibited nonlinear pharmacokinetics at the highest doses tested. While substantially higher concentrations were achieved, the maximum tolerated dose was not established due to this pharmacological limitation. Intermittently-dosed calcitriol was then combined with several antineoplastic agents, including steroids, bisphosphonates and chemotherapeutic agents. The activity seen in a phase II study of weekly calcitriol plus docetaxel was particularly encouraging and led to the development of DN-101, a proprietary formulation designed for cancer treatment. DN-101 in combination with docetaxel is being evaluated in a placebo-controlled randomized clinical trial that has completed accrual. PMID:16886675

  13. Recent Progress in the Treatment of Advanced Prostate Cancer With Intermittent Dose-Intense Calcitriol (DN-101).

    PubMed

    Brawer, Michael K

    2007-01-01

    Docetaxel is becoming standard therapy for androgen-independent prostate cancer (AIPC), and investigational agents are being added to docetaxel to assess potential additive effects and synergy. Although one of these agents, calcitriol, has repeatedly demonstrated antiproliferative properties against cancer of the prostate, breast, colon, and lung, the antineoplastic activity of calcitriol requires superphysiologic levels. Unfortunately, chronic exposure to superphysiologic levels of calcitriol causes hypercalcemia and resulting toxicity. Therefore, a host of analogues of calcitriol have been investigated for antineoplastic function, including intermittent dose-intense calcitriol, or DN-101. Because of encouraging results from phase II studies of DN-101 combined with docetaxel, the ASCENT (AIPC Study of Calcitriol Enhancement of Taxotere) phase II trial investigated docetaxel plus DN-101 versus docetaxel plus placebo in 250 men with metastatic AIPC and an abnormal baseline prostate-specific antigen (PSA) level. Although the ASCENT trial did not achieve its primary endpoint for increased PSA response, there was a significant trend in PSA response rate in the DN-101 arm. DN-101 in combination with docetaxel seems to improve overall survival and, interestingly, has a favorable safety profile compared with docetaxel alone. The DN-101/docetaxel combination is currently being studied in a much larger international trial, ASCENT-2. PMID:17396166

  14. Recent Progress in the Treatment of Advanced Prostate Cancer With Intermittent Dose-Intense Calcitriol (DN-101)

    PubMed Central

    Brawer, Michael K

    2007-01-01

    Docetaxel is becoming standard therapy for androgen-independent prostate cancer (AIPC), and investigational agents are being added to docetaxel to assess potential additive effects and synergy. Although one of these agents, calcitriol, has repeatedly demonstrated antiproliferative properties against cancer of the prostate, breast, colon, and lung, the antineoplastic activity of calcitriol requires superphysiologic levels. Unfortunately, chronic exposure to superphysiologic levels of calcitriol causes hypercalcemia and resulting toxicity. Therefore, a host of analogues of calcitriol have been investigated for antineoplastic function, including intermittent dose-intense calcitriol, or DN-101. Because of encouraging results from phase II studies of DN-101 combined with docetaxel, the ASCENT (AIPC Study of Calcitriol Enhancement of Taxotere) phase II trial investigated docetaxel plus DN-101 versus docetaxel plus placebo in 250 men with metastatic AIPC and an abnormal baseline prostate-specific antigen (PSA) level. Although the ASCENT trial did not achieve its primary endpoint for increased PSA response, there was a significant trend in PSA response rate in the DN-101 arm. DN-101 in combination with docetaxel seems to improve overall survival and, interestingly, has a favorable safety profile compared with docetaxel alone. The DN-101/docetaxel combination is currently being studied in a much larger international trial, ASCENT-2. PMID:17396166

  15. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy.

    PubMed

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  16. Skin conditions: new drugs for managing skin disorders.

    PubMed

    Nguyen, Tam; Zuniga, Ramiro

    2013-04-01

    New drugs are available for managing several common skin disorders. For psoriasis, topical corticosteroids remain the first-line therapy, but topical vitamin D3 analogs, such as calcipotriene, now have a role. They are as effective as medium-potency topical steroids but without steroid side effects, though they can induce hypercalcemia if the dose exceeds 100 g/week. For more severe cases, methotrexate has been widely used, but other drugs now also are prescribed. They include calcineurin inhibitors, such as cyclosporine, and more recently, biologic agents, such as tumor necrosis factor inhibitors. For children and pregnant women, in whom the previously discussed drugs are not appropriate, narrowband UV-B light often is the first-line treatment. For eczema, patients requiring steroid-sparing topical drugs can be treated with calcineurin inhibitors (ie, pimecrolimus or tacrolimus); between the 2, tacrolimus is the first choice for adults and children older than 2 years. When systemic management is needed, oral calcineurin inhibitors (eg, cyclosporine) are appropriate, though oral steroids often are needed for severe cases. The need for systemic management can sometimes be delayed with use of diluted bleach baths. For acne vulgaris, standard treatments with topical benzoyl peroxide and topical or systemic antibiotics are used widely, as are oral contraceptives, but oral isotretinoin is the most effective treatment. PMID:23600334

  17. 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

  18. Tertiary hyperparathyroidism: Is less than a subtotal resection ever appropriate? A study of long-term outcomes

    PubMed Central

    Pitt, Susan C.; Panneerselvan, Rajarajan; Chen, Herbert; Sippel, Rebecca S.

    2010-01-01

    Background Our aim was to examine the outcomes of patients with tertiary hyperparathyroidism (3-HPT) who had limited resection of one or two parathyroids. Methods We reviewed 140 patients with 3-HPT who underwent parathyroidectomy (PTX) at a single institution. Patients were analyzed according to their operation—limited PTX vs. subtotal or total PTX. Results The limited PTX group consisted of 29 patients who underwent resection of one (n=12) or two (n=17) parathyroids. The other 111 patients had subtotal (n=104), total (n=3), and/or reoperative PTX (n=12). The mean follow-up was 79 ± 5 months. Eucalcemia was achieved in 94% of the cases. All patients with persistent (n=2) hypercalcemia underwent subtotal PTX (P=NS vs. limited PTX). In a logistic regression model, the extent of operation was not associated with the development of recurrent disease. Additionally, the incidence of permanent hypocalcemia was 7% after subtotal or total PTX versus 0% following limited resection (P=NS). Conclusions Long-term outcomes in patients with 3-HPT appear to be similar following appropriate limited resection of one or two parathyroid glands compared to subtotal or total PTX. Therefore, a strategy of limited parathyroid resection seems appropriate for patients with 3-HPT when the disease is limited to one or two glands. PMID:19958940

  19. The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Wronski, T. J.; GLOBUS. R.; Levens, M. J.; Morey-Holton, E.

    1983-01-01

    Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia.

  20. CCN3 Impairs Osteoblast and Stimulates Osteoclast Differentiation to Favor Breast Cancer Metastasis to Bone

    PubMed Central

    Ouellet, Véronique; Tiedemann, Kerstin; Mourskaia, Anna; Fong, Jenna E.; Tran-Thanh, Danh; Amir, Eitan; Clemons, Mark; Perbal, Bernard; Komarova, Svetlana V.; Siegel, Peter M.

    2011-01-01

    Bone is a preferred site for breast cancer metastasis, causing pain, fractures, spinal cord compressions, and hypercalcemia, all of which can significantly diminish the patient's quality of life. We identified CCN3 as a novel factor that is highly expressed in bone metastatic breast cancer cells from a xenograft mouse model and in bone metastatic lesions from patients with breast cancer. We demonstrate that CCN3 overexpression enhances the ability of weakly bone metastatic breast cancer cells to colonize and grow in the bone without altering their growth in the mammary fat pad. We further demonstrated that human recombinant CCN3 inhibits osteoblast differentiation from primary bone marrow cultures, leading to a higher receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio. In conjunction with its ability to impair osteoblast differentiation, we uncovered a novel role for CCN3 in promoting osteoclast differentiation from RANKL-primed monocyte precursors. CCN3 exerts its pro-osteoclastogenic effects by promoting calcium oscillations and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation. Together, these results demonstrate that CCN3 regulates the differentiation of bone resident cells to create a resorptive environment that promotes the formation of osteolytic breast cancer metastases. PMID:21514448

  1. Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences.

    PubMed

    2014-01-01

    The goal of this Consensus Statement is to help primary care practitioners achieve adequate vitamin D intake from all sources in their older patients, with the goal of reducing falls and fall-related injuries. The workgroup graded the quality of evidence and assigned an evidence level using established criteria. Based on the evidence for fall and fracture reduction in the clinical trials of older community-dwelling and institutionalized persons and metaanalyses, the workgroup concluded that a serum 25 hydroxyvitamin D (25(OH)D) concentration of 30 ng/mL (75 nmol/L) should be a minimum goal to achieve in older adults, particularly in frail adults, who are at higher risk of falls, injuries, and fractures. The workgroup concluded that the goal--to reduce fall injuries related to low vitamin D status--could be achieved safely and would not require practitioners to measure serum 25(OH)D concentrations in older adults in the absence of underlying conditions that increase the risk of hypercalcemia (e.g., advanced renal disease, certain malignancies, sarcoidosis). PMID:24350602

  2. Effect of ethane-I-hydroxy-I, I-diphosphonate on arterial calcinosis induced by hypervitaminosis D: a morphologic investigation.

    PubMed Central

    Kingma, J. G.; Roy, P. E.

    1990-01-01

    The present study was undertaken to examine changes in vascular ultrastructure of rats subjected to hypervitaminosis D with or without treatment with ethane-I-hydroxy-I, I-diphosphonate (EHDP). Five groups of rats were studied. Untreated rats were given 0.9% NaCl i.p. Sham-treated rats were given vehicle (corn oil). Treated rats were given ergocalciferol (75,000 IU i.p.) dissolved in vehicle with or without EHDP (5 mM/100 g body-weight i.p.). Rats which had been given ergocalciferol without EHDP developed hypercalcemia and demonstrated significant arterial calcinosis. A similar degree of calcinosis was not observed in rats given ergocalciferol with EHDP. EHDP appeared to inhibit arterial calcinosis; however, it did not affect plasma calcium levels. This suggests that EHDP might delay calcium influx into the cell and thereby prevent calcium overload. Our findings support the suggestion that EHDP therapy can be an effective treatment for the inhibition of dystrophic arterial calcinosis. Images Fig. 2 Fig. 3 Fig. 4 PMID:2109995

  3. IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

    PubMed

    Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

    2015-09-01

    IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. PMID:26294067

  4. [Questions about the ADVANCE study].

    PubMed

    Jean, Guillaume; Chazot, Charles

    2012-06-01

    The symptoms of secondary hyperparathyroidism (SHPT) were substantially changed by the availability of cinacalcet (CC). The recent ADVANCE study, which was a prospective randomized trial comparing two treatment strategies-CC plus low doses of calcitriol analogues (CA) versus higher doses of CA without CC-reports the absence of difference in the primary endpoint, i.e. coronary artery calcification score progression after 12 months. The progression of coronary calcification was related to the initial hypercalcemia and hyperphosphataemia, and low serum PTH level. What was the rationale for defining SHPT with only serum PTH value of more than 300 pg/mL or more than 150 pg/mL associated with a high Ca×P product? Why was this coronary score chosen as the primary endpoint and why was a seemingly short observational period used? Is it correct to consider all forms of SHPT equivalent in terms of set point, response to conventional treatment, or vascular and bone consequences? Why are the biological values of patients not provided? Were the CAs, dialysate calcium, and PTH assay values really equal? Why were only calcium-based phosphate binders used? The main controversial point of the study was to consider all HPT cases as equivalent and able to be treated by one fixed strategy. Therefore, the nephrologist community should conduct relevant independent studies in order to improve the diagnosis and treatment of SHPT. PMID:21962855

  5. Severe resistant hypocalcemia in multiple myeloma after zoledronic acid administration: a case report

    PubMed Central

    2014-01-01

    Introduction Hypercalcemia is one of the most common metabolic abnormalities encountered in any form of malignancy. Hypocalcemia, however, is a rare manifestation, especially in cancers with bone involvement. Here we present a case of hypocalcemia in a patient with multiple myeloma that was refractory to treatment. Case presentation A 73-year-old African American woman recently diagnosed with multiple myeloma, presented with a 2-day history of fever, vomiting and hypocalcemia. Ten days prior to admission she received zoledronic acid, Velcade® (bortezomib), Revlimid® (lenalidomide) and dexamethasone. Treatment was started with intravenous antibiotics and calcium gluconate boluses. After 24 hours of treatment her calcium level became undetectable (<5mg/dL). Continuous intravenous calcium gluconate infusions in addition to boluses were started. She remained persistently hypocalcemic and eventually developed tonic–clonic seizures. Vitamin D levels were found to be low and intravenous paricalcitol was initiated, which improved her calcium level. Conclusions Underlying vitamin D deficiency can precipitate severe hypocalcemia in patients with multiple myeloma receiving bisphosphonates. This warrants baseline screening for vitamin D deficiency in these patients. PMID:25342294

  6. An epidemiological perspective of the pathology and etiology of sarcoidosis.

    PubMed

    Sawahata, Michiru; Sugiyama, Yukihiko

    2016-01-01

    To update current knowledge on the pathology and etiology of sarcoidosis, here we review previous epidemiological research and discuss age-related differences and historical changes in the clinical characteristics of sarcoidosis we identified over the last four decades in Japan. Extrathoracic lymph node involvement was more common in young patients, while extrathoracic involvement of non-lymphatic organs and hypercalcemia were more common in older patients. Most patients in their 20s presented with bilateral hilar lymphadenopathy, but this was consistently less common among older patients. Over time, the distribution of age at diagnosis has shifted toward the older age group in the United States, Denmark, and Japan. In Japan, the incidence rate has been decreasing among young people, but there has consistently been a second peak among postmenopausal women. Age-related differences in the clinical presentation of sarcoidosis may reflect the pathways of causative antigens and the strengthening of immunoregulatory mechanisms with age. Internal and external environmental factors, such as exposure to diverse microorganisms, ovarian insufficiency, and active vitamin D deficiency, that may contribute to the onset of sarcoidosis must be identified in order to develop strategies for prevention and treatment. PMID:27537712

  7. Renal confined sarcoidosis: Natural history and diagnostic challenge

    PubMed Central

    Ghafoor, Azam; Almakki, Akram

    2014-01-01

    A 69 year old male referred to nephrology clinic for uncontrolled hypertension. During his follow up over two years, he developed renal disease and hypercalcemia. He was found to have monoclonal gammopathy (MGUS). Urinalysis was negative except for Monoclonal IgG on immunoelectrophoresis. Workup for malignancy was negative including chest X-ray and bone marrow biopsy. He progressed into renal failure and ended up on dialysis. Interestingly, the renal biopsy showed non-caseating granulomas, and the patient was diagnosed with renal confined sarcoidosis which is extremely rare. PPD was negative. He was treated with Prednisone 60 mg daily. Surprisingly, his kidney disease was not responsive to steroids. Despite improvement in his calcium with treatment, his kidney function did not improve and he remained on hemodialysis but needed to stay on small dose of Prednisone to keep his calcium under control. Our case is the first in the literature that demonstrates the natural history of renal-confined sarcoidosis. In addition, the presence of MGUS created a diagnostic challenge and delayed diagnosis of sarcoidosis. Although the renal biopsy did not show direct damage from MGUS, a potential relation between renal sarcoidosis and MGUS is worth studied. PMID:24761384

  8. Genetic defects associated with familial and sporadic hyperparathyroidism.

    PubMed

    Hendy, Geoffrey N; Cole, David E C

    2013-01-01

    Primary hyperparathyroidism (PHPT) occurs sporadically, but occasionally it may be a feature of a familial condition, such as multiple endocrine neoplasia type 1 (MEN1), MEN2A, or the HPT-jaw tumor syndrome (HPT-JT), and familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroidism (FHH/NSHPT). PHPT may also occur as familial isolated hyperparathyroidism (FIHP), and has been observed as a consequence of mutations in the CDKN1B gene (MEN4). Tumorigenesis in these conditions may be the result of protooncogene activation (e.g. RET in MEN2) or two-hit losses of a tumor suppressor (e.g. MEN1, HPT-JT). In patients with MEN1, HPT-JT or FHH/NSHPT, the hyperparathyroidism manifests at a younger age and affects both sexes equally. In MEN1, mutations of the MEN1 gene also cause enteropancreatic and anterior pituitary tumors. In MEN2, activating mutations in the RET protooncogene also cause medullary thyroid carcinoma and pheochromocytoma. In HPT-JT, mutations of CDC73/HRPT2 are associated with parathyroid carcinoma, but tumors of the kidneys and uterus are additional features. In some FIHP families, a CASR mutation may be identified. In parathyroid carcinoma, even if sporadic, molecular diagnostics for CDC73/HRPT2 should be considered, as it should be for younger patients. Further exploration of these hereditary syndromes may shed light on the molecular mechanisms giving rise to nonhereditary PHPT. PMID:23652676

  9. Skeletal metastases from breast cancer: pathogenesis of bone tropism and treatment strategy.

    PubMed

    Fontanella, Caterina; Fanotto, Valentina; Rihawi, Karim; Aprile, Giuseppe; Puglisi, Fabio

    2015-12-01

    Breast cancer (BC) is the most common female cancer worldwide with approximately 10 % of new cases metastatic at diagnosis and 20-50 % of patients with early BC who will eventually develop metastatic disease. Bone is the most frequent site of colonisation and the development of skeletal metastases depends on a complex multistep process, from dissemination and survival of malignant cells into circulation to the actual homing and metastases formation inside bone. Disseminated tumor cells (DTCs) can be detected in bone marrow in approximately 30 % of BC patients, likely reflecting the presence of minimal residual disease that would eventually account for subsequent metastatic disease. Patients with bone marrow DTCs have poorer overall survival compared with patients without them. Although bone-only metastatic disease seems to have a rather indolent behavior compared to visceral disease, bone metastases can cause severe and debilitating effects, including pain, spinal cord compression, hypercalcemia and pathologic fractures. Delivering an appropriate treatment is therefore paramount and ideally it should require interdisciplinary care. Multiple options are currently available, from bisphosphonates to new drugs targeting RANK ligand and radiotherapy. In this review we describe the mechanisms underlying bone colonization and provide an update on existing systemic and locoregional treatments for bone metastases. PMID:26343511

  10. Recent advances in multiple myeloma: a Korean perspective

    PubMed Central

    Hong, Junshik; Lee, Jae Hoon

    2016-01-01

    Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration’s approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea’s trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea. PMID:27604794

  11. Phosphocitrate inhibits mitochondrial and cytosolic accumulation of calcium in kidney cells in vivo.

    PubMed

    Tew, W P; Malis, C D; Howard, J E; Lehninger, A L

    1981-09-01

    Synthetic 3-phosphocitrate, an extremely potent inhibitor of calcium phosphate crystallization as determined in a nonbiological physical-chemical assay, has many similarities to a mitochondrial factor that inhibits crystallization of nondiffracting amorphous calcium phosphate. In order to determine whether phosphocitrate can prevent uptake and crystallization of calcium phosphate in mitochondria in vivo, it was administered intraperitoneally to animals given large daily doses of calcium gluconate or parathyroid hormone, a regimen that causes massive accumulation and crystallization of calcium phosphate in the mitochondria and cytosol of renal tubule cells in vivo. Administration of phosphocitrate greatly reduced the net uptake of Ca2+ by the kidneys and prevented the appearance of apatite-like crystalline structures within the mitochondrial matrix and cytosol of renal tubule cells. Phosphocitrate, which is a poor chelator of Ca2+, did not reduce the hypercalcemia induced by either agent. These in vivo observations therefore indicate that phosphocitrate acts primarily at the cellular level to prevent the extensive accumulation of calcium phosphate in kidney cells by inhibiting the mitochondrial accumulation or crystallization of calcium phosphate. PMID:6946490

  12. GSK-3 Inhibition Sensitizes Acute Myeloid Leukemia Cells to 1,25D-Mediated Differentiation.

    PubMed

    Gupta, Kalpana; Stefan, Tammy; Ignatz-Hoover, James; Moreton, Stephen; Parizher, Gary; Saunthararajah, Yogen; Wald, David N

    2016-05-01

    1,25-dihydroxyvitamin D3 (1,25D), the biologically active form of vitamin D, is widely considered a promising therapy for acute myeloid leukemia (AML) based on its ability to drive differentiation of leukemic cells. However, clinical trials have been disappointing in part to dose-limiting hypercalcemia. Here we show how inhibiting glycogen synthase kinase 3 (GSK3) can improve the differentiation response of AML cells to 1,25D-mediated differentiation. GSK3 inhibition in AML cells enhanced the differentiating effects of low concentrations of 1,25D. In addition, GSK3 inhibition augmented the ability of 1,25D to induce irreversible growth inhibition and slow the progression of AML in mouse models. Mechanistic studies revealed that GSK3 inhibition led to the hyperphosphorylation of the vitamin D receptor (VDR), enabling an interaction between VDR and the coactivator, SRC-3 (NCOA3), thereby increasing transcriptional activity. We also found that activation of JNK-mediated pathways in response to GSK3 inhibition contributed to the potentiation of 1,25D-induced differentiation. Taken together, our findings offer a preclinical rationale to explore the repositioning of GSK3 inhibitors to enhance differentiation-based therapy for AML treatment. Cancer Res; 76(9); 2743-53. ©2016 AACR. PMID:26964622

  13. In vivo demonstration of cell types in bone that harbor epidermal growth factor receptors

    SciTech Connect

    Martineau-Doize, B.; Lai, W.H.; Warshawsky, H.; Bergeron, J.J.

    1988-08-01

    The binding and internalization of (/sup 125/I)iodoepidermal growth factor (EGF) by bone cells of the rat was demonstrated in situ by quantitative radioautography. Specific binding sites were observed on a cell profile enriched in endocytic components, including lysosome-like structures, a rough endoplasmic reticulum-rich cell profile, and a cell profile that histologically resembles an undifferentiated precursor cell. By the criteria of gel filtration and precipitability by trichloroacetic acid, most of the bound (/sup 125/I)iodo-EGF was considered intact. By morphological criteria none of the cell profiles that bound (/sup 125/I)iodo-EGF corresponded to fully formed osteoclasts or osteoblasts. The endocytic cell was found in the epiphyseal plate between the invading capillary and the transverse and longitudinal cartilage septa as well as near osteoclasts in the zone of mixed spicules. The rough endoplasmic reticulum-rich cell was present in vacated chondrocyte lacunae of the epiphyseal plate close to the metaphysis, and the poorly differentiated cell was observed between the mixed spicules of the metaphysis. Similar cell types were also found in the alveolar bone surrounding the incisors. These cells may be the origin of established bone cell lines that harbor high concentrations of EGF receptors and may also be responsible for the humoral hypercalcemia in response to the reported actions of injected EGF or transforming growth factor-alpha as well as that of malignancy.

  14. Potential utility of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism: a case report.

    PubMed

    Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Yamashita, Sumimasa; Nozawa, Kumiko; Masudo, Katsuhiko; Yamakawa, Tadashi; Asakura, Yumi; Hasegawa, Tomonobu; Adachi, Masanori

    2016-07-01

    We report a Japanese pedigree with familial primary hyperparathyroidism due to a CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism. The proband had severe psychomotor retardation and received laryngotracheal separation surgery. At 19 yr of age, he developed acute pancreatitis. Hypercalcemia (12.2-13.8 mg/dL), elevated levels of intact PTH (86-160 pg/mL), and a tumor detected upon neck ultrasonography led to the diagnosis of primary hyperparathyroidism. Family history and biochemical examinations revealed that three family members (the proband's mother, elder brother, and maternal grandfather) had primary hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT, p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding the proband's elder brother who refused genetic testing. Parathyroidectomy for the proband was considered as high-risk, because the tumor was located close to the tracheostomy orifice. After receiving approval from the institutional review board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of age, treatment with 100 mg of cinacalcet maintained serum calcium levels below 11.0 mg/dL with no apparent side effects. Our report presents the potential efficacy of cinacalcet as a treatment for CDC73-related primary hyperparathyroidism, in particularly inoperative cases. PMID:27507909

  15. The endemic mimic: blastomycosis an illness often misdiagnosed.

    PubMed

    Bradsher, Robert W

    2014-01-01

    One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region. PMID:25125734

  16. Adult T-cell leukemia-lymphoma: a clinico-pathologic study of twenty-six patients from Martinique.

    PubMed

    Plumelle, Y; Pascaline, N; Nguyen, D; Panelatti, G; Jouannelle, A; Jouault, H; Imbert, M

    1993-01-01

    Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases. PMID:8113152

  17. 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

  18. Proceedings of the 2013 National Toxicology Program Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Boyle, Michael C.; Boyle, Molly H.; Cora, Michelle C.; Crabbs, Torrie A.; Cummings, Connie A.; Gruebbel, Margarita M.; Johnson, Crystal L.; Malarkey, David E.; McInnes, Elizabeth F.; Nolte, Thomas; Shackelford, Cynthia C.; Ward, Jerrold M.

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Portland, Oregon in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen induced hepatoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  19. Canagliflozin-induced pancreatitis: a rare side effect of a new drug.

    PubMed

    Chowdhary, Mudit; Kabbani, Ahmad A; Chhabra, Akansha

    2015-01-01

    Acute pancreatitis is most commonly attributed to gallstones, alcohol abuse, and metabolic disorders such as hyperlipidemia and hypercalcemia. Medications are an infrequent yet commonly overlooked etiology of pancreatitis. Although several drugs have been implicated, antidiabetic agents are a rare cause for drug-induced pancreatitis. Canagliflozin is a new drug in the class of SGLT-2 inhibitors used for the treatment of type 2 diabetes mellitus. Serious reported side effects include renal impairment, hyperkalemia, and hypotension. Pancreatitis as a result of canagliflozin, however, is exceedingly rare. Here we describe a case of a 33-year old female who presented with severe acute pancreatitis in the setting of recent initiation of canagliflozin. Given the timing of her presentation and after excluding all other possible etiologies, it was determined that canagliflozin was the likely source of her illness. This case highlights the importance of identifying drug-induced pancreatitis, especially in novel drugs, as it is commonly neglected in patients with multiple medical comorbidities and those taking numerous medications. Prompt identification of drug-induced pancreatitis can improve management as well as decrease morbidity and mortality in these individuals. PMID:26170677

  20. A Novel Mutation in a Patient with Hyperparathyroidism-Jaw Tumour Syndrome.

    PubMed

    Bellido, Virginia; Larrañaga, Ihintza; Guimón, Maite; Martinez-Conde, Rafael; Eguia, Asier; Perez de Nanclares, Gustavo; Castaño, Luis; Gaztambide, Sonia

    2016-06-01

    Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is a rare variant of familial hyperparathyroidism, characterized by primary hyperparathyroidism (PHPT) due to one or multiple parathyroid adenomas, and benign tumours of the mandible and maxilla. It has an autosomal dominant pattern of inheritance, and is associated with mutations that deactivate the cell division cycle protein 73 homolog (CDC73) gene, also known as hyperparathyroidism 2 (HRPT2), located on the long arm of chromosome 1, that encodes for the tumour suppressor protein parafibromin. In the majority of cases, PHPT is the presenting symptom, but up to 30 % of HPT-JT cases initially present with an ossifying fibroma of the maxillofacial bones. HPT-JT may result in severe hypercalcemia-related complications and an elevated risk of parathyroid carcinoma. For this reason, early identification of the disease is important. We present the case of a 23-year-old woman who was found to have jaw tumours and was later diagnosed with PHPT. Genetic analysis revealed a novel mutation in exon 1 of CDC73. This report contributes to the understanding of the genetics of this rare syndrome. It also highlights the fact that HPT-JT should be considered and CDC73 mutation analysis should be performed in cases of early-onset PHPT associated with ossifying fibromas of the jaw. PMID:26995009

  1. [Radionuclide therapy for the treatment of skeletal metastases of urological malignancies: a forgotten therapy?].

    PubMed

    Badawi, J K

    2012-08-01

    Many patients suffering from urological or non-urological malignancies develop bone metastases. One symptom often found is severe skeletal pain which siginificantly lowers the quality of life. Further symptoms are pathological fractures, spinal cord compression and hypercalcemia. The systemic radiopharmaceutical therapy represents an important systemic treatment option, in addition to chemotherapy, hormone therapy, external beam radiation, bisphosphonates and analgesics. The radionuclide therapy is rarely used and often used in a later phase of disease, mainly known for the bone pain palliation. This review article should help remind physicians to use this interesting therapy. It focuses on the common radionuclides Strontium-89-chloride, Samarium-153-EDTMP (ethylene-diamine-tetra-methylene-phosphonate) and Rhenium-186-HEDP (hydroxyethylidene-diphosphonate), their physical characteristics and differences, contraindications of the therapy like spinal cord compression and side effects. Additionally, potential tumoricidal activity and improvement of survival are discussed when using the radionuclides repetitively or in combination. The European and German guidelines are included. Furthermore, the combination of radionuclides and bisphosphonates or chemotherapy are briefly discussed, based on available clinical studies. Additionally, alpharadin (radium-223 chloride) is discussed, an experimental radiopharmaceutical under clinical evaluation, which emits alpha-radiation. In phase III clinical trials, it was shown to significantly increase the median overall survival in patients with bone metastases from advanced prostate cancer. PMID:22875692

  2. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain.

    PubMed

    Paes, Fabio M; Serafini, Aldo N

    2010-03-01

    Bone pain due to skeletal metastases constitutes the most common type of chronic pain among patients with cancer. It significantly decreases the patient's quality of life and is associated with comorbidities, such as hypercalcemia, pathologic fractures and spinal cord compression. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will have symptomatic skeletal metastases. The management of bone pain is extremely difficult and involves a multidisciplinary approach, which usually includes analgesics, hormone therapies, bisphosphonates, external beam radiation, and systemic radiopharmaceuticals. In patients with extensive osseous metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. In this article, we review the current approved radiopharmaceutical armamentarium for bone pain palliation, focusing on indications, patient selection, efficacy, and different biochemical characteristics and toxicity of strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate. A brief discussion on the available data on rhenium-188 is presented focusing on its major advantages and disadvantages. We also perform a concise appraisal of the other available treatment options, including pharmacologic and hormonal treatment modalities, external beam radiation, and bisphosphonates. Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy are discussed. PMID:20113678

  3. Paraneoplastic syndromes associated with lung cancer

    PubMed Central

    Kanaji, Nobuhiro; Watanabe, Naoki; Kita, Nobuyuki; Bandoh, Shuji; Tadokoro, Akira; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

    2014-01-01

    Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer. PMID:25114839

  4. Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice

    PubMed Central

    Dong, Anliang; Lu, Yan; Lu, Bingjian

    2016-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy worldwide. Recent advance in genomic/epigenomic researches will impact on our prevention, detection and intervention on ovarian carcinoma. Detection of germline mutations in BRCA1/BRCA2, mismatch repair genes, and other genes in the homologous recombination/DNA repair pathway propelled the genetic surveillance of most hereditary ovarian carcinomas. Germline or somatic mutations in SMARCA4 in familial and sporadic small cell carcinoma of the ovary, hypercalcemia type, lead to our recognition on this rare aggressive tumor as a new entity of the atypical teratoma/rhaboid tumor family. Genome-wide association studies have identified many genetic variants that will contribute to the evaluation of ovarian carcinoma risk and prognostic prediction. Whole exome sequencing and whole genome sequencing discovered rare mutations in other drive mutations except p53, but demonstrated the presence of high genomic heterogeneity and adaptability in the genetic evolution of high grade ovarian serous carcinomas that occurs in cancer progression and chemotherapy. Gene mutations, copy number aberrations and DNA methylations provided promising biomarkers for the detection, diagnosis, prognosis, therapy response and targets of ovarian cancer. These findings underscore the necessity to translate these potential biomarkers into clinical practice. PMID:27471560

  5. 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

  6. Myeloma today: Disease definitions and treatment advances.

    PubMed

    Rajkumar, S Vincent

    2016-01-01

    There have been major advances in the diagnosis, staging, risk-stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) features, new diagnostic criteria include three new biomarkers to diagnose the disease: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging. MM can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities. A Revised International Staging System has been developed which combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high-risk cytogenetics and elevated serum lactate dehydrogenase). Although the approach to therapy remains largely the same, the treatment options at every stage of the disease have changed. Carfilzomib, pomalidomide, panobinostat, daratumumab, elotuzumab, and ixazomib have been approved for the treatment of the disease. These drugs combined with older agents such as cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide dramatically increase the repertoire of regimens available for the treatment of MM. This review provides a concise overview of recent advances in MM, including updates to diagnostic criteria, staging, risk-stratification, and management. PMID:26565896

  7. Simultaneous presentation of giant pheochromocytoma, primary hyperparathyroidism, and mixed-medullary-papillary thyroid cancer in MEN 2A.

    PubMed

    Gupta, Vishal

    2013-07-01

    The aim of this study was to describe a young man with probably the largest pheochromocytoma associated with MEN 2A, described till date. The patient, a non-vegetarian, fifth of eight siblings, married, having five children, presented with episodes of difficult-to-control hypertension requiring over five antihypertensives. He was referred to us with an abdominal CT scan that revealed a 16 cm left-sided adrenal mass. Biochemical testing confirmed a catecholamine secreting pathology. Histopathology confirmed the mass as a pheochromocytoma weighing 1.8 kg. Further evaluation suggested a parathormone-dependent hypercalcemia and a left-sided thyroid mass. Histopathology confirmed parathyroid hyperplasia and medullary carcinoma of the thyroid mixed with papillary carcinoma of thyroid. Putting all the findings together showed that the patient was suffering from multiple endocrine neoplasia 2. Multiple endocrine neoplasia 2A is a rare syndrome. The case is unique in the way it presented, with all the three tumors at the same time. The management was bold and addressed all the three lesions in the same hospital admission. We are also reporting the largest described case of pheochromocytoma from India. PMID:23961501

  8. Multifocal Insulinoma in Pancreas and Effect of Intraoperative Ultrasonography

    PubMed Central

    Borazan, Ersin; Aytekin, Alper; Yilmaz, Latif; Elci, Muhsin; Karaca, Mehmet Salih; Kervancioglu, Selim; Balik, Ahmet Abdulhalik

    2015-01-01

    Insulinoma is the most frequently seen functional pancreatic neuroendocrine tumor. The incidence of multifocal insulinoma is lower than 10%. Its treatment is direct or laparoscopic excision. The present case was examined with the findings of hypoglycemia and hypercalcemia, and as there was high insulin and C-peptide levels the initial diagnosis was insulinoma. The case was investigated in terms of MEN 1. During preoperative screening for localization, there was one focus in the head of the pancreas in the abdominal tomography and two foci in endoscopic ultrasonography. No other focus was detected through intraoperative visual or manual palpation. However, five foci were detected during operation by intraoperative ultrasonography. The relation of masses with the main pancreatic canal was evaluated and they were excised by enucleation method. There was no recurrence during the postoperative 18-month follow-up of the patient. As a result, during treatment for insulinoma, it should be kept in mind that there might be multifocal foci. In all insulinomas, the whole pancreas should be evaluated with intraoperative ultrasonography because none of the current preoperative diagnostic methods are as sensitive as manual palpation of pancreas and intraoperative ultrasonography. The intraoperative detection of synchronous five foci in pancreas is quite a rare condition. PMID:26295000

  9. 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

  10. 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

  11. Acid Secretion and Serum Gastrin Levels in the Zollinger-Ellison Syndrome

    PubMed Central

    Sanchez, R. Edward; Longmire, William P.; Passaro, Edward

    1972-01-01

    Thirteen cases of patients with the Zollinger-Ellison syndrome were reviewed. In two cases the diagnosis was made by incidental biopsy of small liver nodules at operation for peptic ulcer disease. Seven patients had gastric secretory tests which showed a basal acid output to maximum acid output ratio of more than 65 percent. Five patients had bao:mao ratios less than 50 percent. A 30-month interval between incidental discovery of tumor and clinically evident disease was observed in two patients. Recurrence of symptoms after excision of tumor was noted after a similar interval in another case. Serum gastrin levels, before total gastrectomy, were elevated in all cases. The lowest preoperative level in this series of patients was 550 picograms per ml (normal 100 to 150 picograms). They were diagnostic in two patients with normal gastric secretory studies. The levels fell to normal following total gastrectomy in six patients. Two patients still had elevated levels five years and 14 years after total gastrectomy. One was discovered to have a parathyroid adenoma with hypercalcemia. Total gastrectomy was curative in all the patients with the Zollinger-Ellison syndrome; lesser operations were not. ImagesFigure 1.Figure 2.Figure 3.Figure 3.Figure 4. PMID:5031740

  12. Management of the adverse effects associated with intravenous bisphosphonates.

    PubMed

    Tanvetyanon, T; Stiff, P J

    2006-06-01

    Intravenous bisphosphonates are widely used to treat hypercalcemia and to reduce skeletal-related morbidity among cancer patients. However, serious complications, generally occurring in less than 2% of patients participated in phase III clinical trials, including acute systemic inflammatory reaction, ocular inflammation, renal failure, nephrotic syndrome, electrolyte imbalance, and osteonecrosis of the maxilla and mandible have all been increasingly reported. Yet, strategies to deal with these complications are becoming clear. Acute systemic inflammatory reaction is often self-limited and becomes less intense during subsequent treatments. For patients who develop ocular symptoms, prompt ophthalmologic evaluation is crucial to determine the safety of a subsequent bisphosphonate therapy. Patients who receive long-term pamidronate should be evaluated at intervals for early sign of nephritic syndrome as timely cessation of the agent may result in a full recovery. To reduce the risk of severe electrolyte abnormalities, particularly hypocalcemia, correcting any pre-treatment electrolyte abnormality and supplementing vitamin D and calcium may be helpful. Finally, to reduce the risk of osteonecrosis of the maxilla and mandible, obtaining a full dental evaluation before treatment and avoidance of invasive dental procedures is suggested. The three commonly used intravenous bisphosphonates (pamidronate, zoledronic acid, and ibandronate), are generally safe; ibandronate has to date been the least reported to be associated with renal side effects. As clinical indications of intravenous bisphosphonates continue to expand, prescribing clinicians should be familiar with these possible adverse effects and discuss them with patients before commencing or continuing on therapy. PMID:16547070

  13. Extensive Bone Marrow Necrosis and Osteolytic Lesions in a Case of Acute Myeloid Leukemia Transformed from Polycythemia Vera.

    PubMed

    Chambers, Isaac; Truong, Phu; Kallail, K James; Palko, William

    2016-01-01

    Acute myeloid leukemia (AML) is the most common leukemia in adults. In rare cases, bone marrow necrosis (BMN) and osteolytic lesions are presenting features of AML. The following case describes a patient with known polycythemia vera (PV) that presented with signs of multiple myeloma, including hypercalcemia, anemia, and lytic lesions of the thoracic spine and skull. Laboratory workup was not indicative of myeloma. A bone marrow biopsy was performed, which revealed extensive BMN and initial pathology was consistent with metastatic carcinoma. However, no immunohistochemical stains could be performed due to the extent of BMN; a repeat biopsy was therefore performed. Flow cytometry and CD45 staining were consistent with PV that had transformed to AML. Due to the patient's comorbidities, she was a poor candidate for stem cell transplant and did not wish to pursue chemotherapy. Ultimately, she pursued hospice care. Based on our literature review, both BMN and osteolytic lesions are rare manifestations of AML and have not been reported to occur simultaneously. These findings can lead to a diagnostic dilemma and suspicion of other malignancies. This case demonstrates that AML should remain in the differential diagnosis in those patients who present with BMN and osteolytic lesions. PMID:27433418

  14. Extensive Bone Marrow Necrosis and Osteolytic Lesions in a Case of Acute Myeloid Leukemia Transformed from Polycythemia Vera

    PubMed Central

    Truong, Phu; Kallail, K. James; Palko, William

    2016-01-01

    Acute myeloid leukemia (AML) is the most common leukemia in adults. In rare cases, bone marrow necrosis (BMN) and osteolytic lesions are presenting features of AML. The following case describes a patient with known polycythemia vera (PV) that presented with signs of multiple myeloma, including hypercalcemia, anemia, and lytic lesions of the thoracic spine and skull. Laboratory workup was not indicative of myeloma. A bone marrow biopsy was performed, which revealed extensive BMN and initial pathology was consistent with metastatic carcinoma. However, no immunohistochemical stains could be performed due to the extent of BMN; a repeat biopsy was therefore performed. Flow cytometry and CD45 staining were consistent with PV that had transformed to AML. Due to the patient’s comorbidities, she was a poor candidate for stem cell transplant and did not wish to pursue chemotherapy. Ultimately, she pursued hospice care. Based on our literature review, both BMN and osteolytic lesions are rare manifestations of AML and have not been reported to occur simultaneously. These findings can lead to a diagnostic dilemma and suspicion of other malignancies. This case demonstrates that AML should remain in the differential diagnosis in those patients who present with BMN and osteolytic lesions.  PMID:27433418

  15. Hyperparathyroidism after treatment with radioactive iodine: Not only a coincidence

    SciTech Connect

    Bondeson, A.G.; Bondeson, L.; Thompson, N.W. )

    1989-12-01

    Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 ({sup 131}I) treatment. In seven cases {sup 131}I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with {sup 131}I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from {sup 131}I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context.

  16. Chronic beryllium disease: Diagnosis and management

    SciTech Connect

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  17. Anatomic Site Variability in Rat Skeletal Uptake and Desorption Of Fluorescently Labeled Bisphosphonate

    PubMed Central

    Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S.O.

    2010-01-01

    Objectives Bisphosphonates commonly used to treat osteoporosis, Paget’s disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. Materials and Methods Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. Results Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was highest in oral relative to axial and appendicular bones (p < 0.05). Conclusions This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial and appendicular bones of immune deficient rats. PMID:21122034

  18. Proceedings of the 2013 National Toxicology Program Satellite Symposium.

    PubMed

    Elmore, Susan A; Boyle, Michael C; Boyle, Molly H; Cora, Michelle C; Crabbs, Torrie A; Cummings, Connie A; Gruebbel, Margarita M; Johnson, Crystal L; Malarkey, David E; McInnes, Elizabeth F; Nolte, Thomas; Shackelford, Cynthia C; Ward, Jerrold M

    2014-01-01

    The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Portland, Oregon, in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen-induced hepatotoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions of the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

  19. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    PubMed

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease. PMID:27208626

  20. Isolation of a murine osteoclast colony-stimulating factor.

    PubMed Central

    Lee, M Y; Eyre, D R; Osborne, W R

    1991-01-01

    Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrate-resistant acid phosphatase (TRAPase) activity. These TRAPase-positive cells demonstrated essential features of osteoclasts when cultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-forming cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel filtration chromatography and reverse-phase HPLC. By SDS/PAGE, the activity was traced to a protein of approximately 17 kDa. Functional and biochemical studies of the purified factor suggest that it is distinct from any known CSF of myeloid cells. This protein appears to be a CSF for the osteoclast lineage, osteoclast CSF (O-CSF). Images PMID:1924309

  1. MRI detection of early bone metastases in B16 mouse melanoma models

    PubMed Central

    Gauvain, Karen M.; Garbow, Joel R.; Song, Sheng-Kwei; Hirbe, Angela C.; Weilbaecher, Katherine

    2009-01-01

    Bone metastasis causes significant morbidity in cancer patients, including bone pain, pathologic fractures, nerve compression syndrome, and hypercalcemia. Animal models are utilized to study the pathogenesis of skeletal metastases and to evaluate potential therapeutic agents. Previously published methods for imaging bone metastasis in rodent models have focused on identifying advanced stage metastasis using simple X-rays. Here we report MRI as a method for detecting early bone metastases in mouse models in vivo. B16 mouse melanoma cells were injected into the left cardiac ventricle of C57BL/6 mice and magnetic resonance (MR) images were obtained of the left leg following the development of metastatic disease, when tumor associated bone destruction was histologically present but not visible by X-ray. T1 and T2 relaxation times of bone marrow were measured in healthy control mice and B16 melanoma tumor-bearing mice. Mean T2 values for normal marrow were 28 ms (SD 5) and for diseased bone marrow were 41 ms (SD 3). T2 relaxation time of diseased bone marrow is significantly longer than that of normal bone marrow (P < 0.0001) and can be used as a marker of early bone metastases. These studies demonstrate that MR imaging can detect bone marrow metastases in small animals prior to development of cortical bone loss identified by X-ray. PMID:16283483

  2. Gallium increases bone calcium and crystallite perfection of hydroxyapatite.

    PubMed

    Bockman, R S; Boskey, A L; Blumenthal, N C; Alcock, N W; Warrell, R P

    1986-12-01

    Gallium, a group IIIa metal, is known to interact with hydroxyapatite as well as the cellular components of bone. In recent studies we have found gallium to be a potent inhibitor of bone resorption that is clinically effective in controlling cancer-related hypercalcemia as well as the accelerated bone resorption associated with bone metastases. To begin to elucidate gallium's mechanism of action we have examined its effects on bone mineral properties. After short-term (14 days) administration to rats, gallium nitrate produced measurable changes in bone mineral properties. Using atomic absorption spectroscopy, low levels of gallium were noted to preferentially accumulate in regions of active bone formation, 0.54 +/- .07 microgram/mg bone in the metaphyses versus 0.21 +/- .03 microgram/mg bone in the diaphyses, P less than 0.001. The bones of treated animals had increased calcium content measured spectrophotometrically. Rats injected with radiolabeled calcium during gallium treatment had greater 45-calcium content compared to control animals. By wide-angle X-ray analyses, larger and/or more perfect hydroxyapatite was observed. The combined effects of gallium on bone cell function and bone mineral may explain its clinical efficacy in blocking accelerated bone resorption. PMID:3026592

  3. Calcification of the aortic wall in hypercalcemic rabbits.

    PubMed

    Rokita, E; Cichocki, T; Divoux, S; Gonsior, B; Höfert, M; Jarczyk, L; Strzałkowski, A

    1992-10-01

    The mineralization process was investigated in the aortic wall of hypercalcemic rabbits. The elevated calcium level in serum was induced by intramuscular injection of vitamin D3. The animals were killed at different times of the experiment (max. 246 d). The freeze-dried tissue homogenates were used for elemental composition studies by means of proton induced X-ray emission (PIXE) and atomic absorption spectroscopy. The structural information was obtained from infrared (IR) and X-ray diffraction (XRD) spectra. Moreover, the ascending part of the aortic arch was separated and used for micro-PIXE (PIXE in combination with proton microprobe) and histochemical examinations. It was found that hypercalcemia (blood serum Ca content elevated by about 20%) induced calcification of the aortic wall. The mineral phase within the aortic wall consisted of Ca-P salts. The Ca/P ratio continuously increased during the experiment and approached 2 after 246 d of the vitamin D3 treatment. The IR and XRD studies made possible the identification of the complex phase composition of the samples. The hydroxyapatite crystals were detected after 196 days, however, in earlier phases of the experiment, amorphous calcium phosphate, dicalcium phosphate dihydrate and octacalcium phosphate were also observed. On the basis of the data obtained, the mechanism of the precipitation and growth of inorganic deposits in the tunica media of the aortic wall was discussed. PMID:1333314

  4. An Unusual Cause of Altered Mental Status in Multiple Myeloma: An Extraosseous Manifestation.

    PubMed

    Jaruvongvanich, Veeravich; Spanuchart, Ittikorn; O-Charoen, Pichaya; Kitamura, Christian; Sumida, Lauren; Roytman, Marina

    2016-04-01

    Multiple myeloma typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Extraosseous manifestations are rare. We report on a patient who was recently diagnosed with multiple myeloma and completed the first cycle of bortezomib, dexamethasone, and palliative radiation therapy with good response. Two weeks after discharge, she became confused and was re-admitted. Despite treatment with lactulose and rifaximin, altered mental status worsened. Computer tomographic scan of abdomen showed hepatomegaly and numerous ill-defined small hyperdense nodules scattered throughout the liver. Liver biopsy demonstrated aggregation of plasma cell myeloma. Magnetic resonance imaging of brain revealed dural thickening. Patient's altered mental status was likely from leptomeningeal myelomatosis and hyperammonemic encephalopathy. Although extraosseous manifestations in multiple myeloma including liver and leptomeningeal involvement are rare, its incidence has increased. This condition portends a poor prognosis. The non-specific manifestations of extraosseous myeloma can be confused with complications of multiple sclerosis and lead to incorrect management, thus clinicians should be aware of these pathologies and perform proper diagnostic tests including imaging and tissue pathology. The most effective treatment is unknown, however bortezomib and thalidomide show promise. PMID:27099806

  5. Antitumor effect of temsirolimus against oral squamous cell carcinoma associated with bone destruction.

    PubMed

    Okui, Tatsuo; Shimo, Tsuyoshi; Fukazawa, Takuya; Kurio, Naito; Hassan, Nur Mohammad Monsur; Honami, Tatsuki; Takaoka, Munenori; Naomoto, Yoshio; Sasaki, Akira

    2010-11-01

    The mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous cell carcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR inhibitor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, we investigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral squamous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. Significantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. Reverse transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor activator for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 cells. Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral hypercalcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma. PMID:20858724

  6. Fat-Soluble Vitamin Status in Self-Neglecting Elderly

    NASA Technical Reports Server (NTRS)

    Kala, G.; Oliver, S. Mathews; Kelly, P. A.; Pickens, S.; Burnett, J.; Dyer, C. B.; Smith, S. M.

    2006-01-01

    Elder self-neglect is a form of elder mistreatment. The systematic characterization of self-neglecting individuals is the goal of the CREST project. Reported here is the evaluation of fat-soluble vitamin status. Self-neglect (SN) subjects were recruited and consented following referral from Adult Protective Services. Control (CN) subjects were matched for age, gender, race, and socioeconomic status, as possible. We report here on 47 SN subjects (age 77 plus or minus 7, mean plus or minus SD; body weight 76 kg plus or minus 26) and 40 CN subjects (77 y plus or minus 7, 79 kg plus or minus 20). Blood samples were analyzed for indices of fat-soluble vitamin status. Plasma retinol (p less than 0.01) was lower in SN subjects. Plasma tocopherol tended (p less than 0.06) to be lower in SN subjects, while gamma-tocopherol was unchanged. SN subjects tended to have lower serum 25-OH vitamin D (p less than 0.11), and to be vitamin D deficient (26% below 23 mmol/L). Hypercalcemia occurred more often in SN subjects (23% had values above 2.56 mmol/L), as did elevated parathyroid hormone concentrations (p less than 0.05). These data demonstrate that many nutrients are affected in the self-neglecting elderly, and that long-term deficits are evident by the nature of changes in fat soluble vitamins.

  7. Solitary Extramedullary Plasmacytoma of the Maxillary Sinus, Progressing to Smoldering Multiple Myeloma with Multifocal Skeletal Involvement, which Resolved Completely Following Chemotherapy Alone.

    PubMed

    Jeyaraj, Priya; Venkatesan, Manu; Nijhawan, V S

    2016-07-01

    Plasmacytoma is an uncommon malignant tumor originating either from plasma cells located in the bone marrow also known as the solitary bone plasmacytoma, or from plasma cells located outside the bone, for e.g. in mucosal surfaces, referred to as the extramedullary plasmacytoma also called the solitary extramedullary plasmacytoma. Both, solitary as well as extramedullary bone plasmacytomas may, particularly in later stages, be accompanied by other osteolytic bone lesions (multifocal bone involvement) and features such as anemia, hypercalcemia, or renal impairment attributable to and indicative of progression to multiple myeloma. These three distinct disorders together comprise the plasma cell neoplasms and essentially represent a continuum of related disease processes. Extramedullary and solitary bone plasmacytomas of the head and neck region are extremely uncommon, and amongst them plasmacytoma of the maxilla is extremely rare. Such a case is being reported here for its rarity. Also, it was associated with multifocal skeletal involvement, making a correct categorization difficult as well as imperative in order to institute the correct treatment. Radiotherapy is considered to be the treatment of choice of plasmacytoma, with adjuvant chemotherapy for multi focal involvement. Surgery is usually limited to biopsy and excision of any residual disease following radiotherapy. The case presented responded extremely well to chemotherapy alone, with a complete resolution of the maxillary tumor, obviating the need for radiotherapy. PMID:27408443

  8. Updated Diagnostic Criteria and Staging System for Multiple Myeloma.

    PubMed

    Rajkumar, S Vincent

    2016-01-01

    There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease. These changes enable early diagnosis and allow the initiation of effective therapy to prevent the development of end-organ damage for patients who are at the highest risk. A new staging system has been developed that incorporates high-risk cytogenetic abnormalities in addition to standard laboratory markers of prognosis. PMID:27249749

  9. Exome Sequencing Identifies a Novel Homozygous Mutation in the Phosphate Transporter SLC34A1 in Hypophosphatemia and Nephrocalcinosis

    PubMed Central

    Rajagopal, Abbhirami; Braslavsky, Débora; Lu, James T.; Kleppe, Soledad; Clément, Florencia; Cassinelli, Hamilton; Liu, David S.; Liern, Jose Miguel; Vallejo, Graciela; Bergadá, Ignacio; Gibbs, Richard A.; Campeau, Phillipe M.

    2014-01-01

    Context: Two Argentinean siblings (a boy and a girl) from a nonconsanguineous family presented with hypercalcemia, hypercalciuria, hypophosphatemia, low parathyroid hormone (PTH), and nephrocalcinosis. Objective: The goal of this study was to identify genetic causes of the clinical findings in the two siblings. Design: Whole exome sequencing was performed to identify disease-causing mutations in the youngest sibling, and a candidate variant was screened in other family members by Sanger sequencing. In vitro experiments were conducted to determine the effects of the mutation that was identified. Patients and Other Participants: Affected siblings (2 y.o. female and 10 y.o male) and their parents were included in the study. Informed consent was obtained for genetic studies. Results: A novel homozygous mutation in the gene encoding the renal sodium-dependent phosphate transporter SLC34A1 was identified in both siblings (c.1484G>A, p.Arg495His). In vitro studies showed that the p.Arg495His mutation resulted in decreased phosphate uptake when compared to wild-type SLC34A1. Conclusions: The homozygous G>A transition that results in the substitution of histidine for arginine at position 495 of the renal sodium-dependent phosphate transporter, SLC34A1, is involved in disease pathogenesis in these patients. Our report of the second family with two mutated SLC34A1 alleles expands the known phenotype of this rare condition. PMID:25050900

  10. [Risk assessment in patients undergoing osseous antiresorptive therapy in dentistry. An update].

    PubMed

    Borm, Jan M; Moser, Stephanie; Locher, Michael; Damerau, Georg; Stadlinger, Bernd; Grätz, Klaus W; Jacobsen, Christine

    2013-01-01

    Antiresorptive therapy is prescribed in particular for the treatment of osteoporosis as well as for the treatment of tumor-induced hypercalcemia and metastatic bone disease. As a consequence, osteopathologies such as bisphosphonate-related osteonecrosis of the jaws (BRONJ) may occur. In 2008, our department reported on BRONJ in a paper that provided dental clinicians with information on diagnostics, therapy, and prevention (Dannemann et al., Schweizer Monatsschrift für Zahnmedizin, Vol. 118, 2/2008). During the last 8 years, new findings have emerged concerning potential etiologies, modes of therapy, and the use of additional antiresorptive therapies. For example, an important point for colleagues in dental practice is the now common intravenous administration of bisphosphonates in osteoporosis patients, which may lead to uncertainty when assessing risk in these patients. For this reason, this article provides an update of the above mentioned publication and gives dental clinicians an updated guideline concerning risk assessment in patients undergoing antiresorptive therapy. In this context, a risk assessment algorithm is presented. The pathogenesis, diagnosis, therapy, and prevention of BRONJ and oral implantation in patients receiving antiresorptive therapy are addressed with regard to the current literature. Finally, we present two example cases. PMID:24420526

  11. Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer

    SciTech Connect

    Huang, Chuan-Hsiang; Gabelli, Sandra B.; Oldfield, Eric; Amzel, L. Mario

    2010-11-15

    Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS.

  12. Adult T-Cell Lymphoma/Leukemia Presenting as Isolated Central Nervous System T-Cell Lymphoma

    PubMed Central

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  13. When normal is abnormal: keys to laboratory diagnosis of hidden endocrine disease.

    PubMed

    Graves, Thomas K

    2011-05-01

    Although veterinary clinicians commonly rely on panels of laboratory tests with individual results flagged when abnormal, care should be taken in interpreting normal test results as well. There are several examples of this in evaluating patients with endocrine disease. The finding of a normal leukogram (absence of a stress leukogram) can be indicative of adrenal insufficiency in dogs, and this disorder can be especially elusive when there are no overt indicators of mineralocorticoid deficiency. Cats with hyperthyroidism can have normal serum thyroid hormone concentrations, normal hematocrits, and normal serum concentrations of creatinine despite the presence of disease that affects these parameters. A normal serum phosphorus concentration, in the face of azotemia, isosthenuria, and hypertension can point a clinician toward a diagnosis of primary hyperaldosteronism rather than primary renal disease. A normal serum parathyroid hormone concentration in the face of hypercalcemia is inappropriate and can indicate the presence of primary hyperparathyroidism. Similarly, hypoglycemia accompanied by a normal serum insulin concentration can be found in cases of hyperinsulinism. These normal findings in abnormal patients, and their mechanisms, are reviewed. PMID:21596344

  14. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  15. Acute effects of Solanum malacoxylon on bone formation rates in growing rats.

    PubMed

    Norrdin, R W; de Barros, C S; Queille, M L; Carré, M; Miravet, L

    1979-11-01

    The plant Solanum malacoxylon is responsible for a syndrome of hypercalcemia, soft tissue mineralization, and progressive wasting in South American cattle known as enteque seco or espichamento. There is evidence that a glycoside of 1,25-dihydroxycholecalciferol is the active principle in the plant. The basis for the hyperostosis seen in the disease is unclear. To study the acute effects on bone formation rates, 8-week-old rats were given an aqueous extract equivalent to 250 or 1000 mg of Solanum daily per os for 7 days. Bones were labeled by injection of fluochrome 2 days before the start of treatment and 2 days prior to sacrifice. Morphometric evaluation of undecalcified sections of caudal vertebrae revealed an increased amount of trabecular bone in both Solanum treated groups with no difference due to dose level. This was associated with an increase in the bone apposition rate on trabecular surfaces. No differences were found in the amount of osteoid seam width. Periosteal apposition rate and endochondral bone formation were also measured and no significant differences found. The findings indicate that acute stimulation of cell level bone formation on trabecular surfaces may play a role in the hyperostosis seen in the naturally occurring condition. PMID:116737

  16. A case of nasal septal abscess caused by medication related osteonecrosis in breast cancer patient.

    PubMed

    Maeda, Mayuka; Matsunobu, Takeshi; Kurioka, Takaomi; Kurita, Akihiro; Shiotani, Akihiro

    2016-02-01

    Antiresorptive drugs have been widely used to treat patients with hypercalcemia caused by malignancy, bone metastasis, multiple myeloma, and osteoporosis. However, it is well known that antiresorptive drugs can cause osteonecrosis of the jaw (ONJ). Herein, we report a rare case of nasal septal abscess caused by medication related osteonecrosis of the jaw (MRONJ) in a breast cancer patient. A 69-year-old woman was referred to our clinic for evaluation of nasal obstruction. Physical examination revealed a cherry-like swelling of the nasal mucosa emanating from the septum that obstructed both nasal cavities and a fistulous tract showing pus discharge after extraction of the bilateral maxillary central incisors (MCI) and the right maxillary lateral incisor (MLI). Computed tomography and panoramic radiography revealed extensive osteonecrosis of the maxilla and swelling of the nasal mucosa. The clinical diagnosis was nasal septal abscess caused by osteonecrosis of the maxilla. Surgical procedure was undertaken for this case. An indwelling drain was placed in the oral cavity, and sequestrectomy was performed with incision and drainage of the anterior portion of left nasal septum. The patient was doing well at the 7-month follow-up. The patient had a medical history of breast cancer with bone, lung, liver metastases, and had received intravenous bisphosphonate, which is one of the antiresorptive medicines, over the past 4 years. We suspect that this history played an important role in MRONJ induced nasal septal abscess. PMID:26775849

  17. The phosphatonins and the regulation of phosphate transport and vitamin D metabolism.

    PubMed

    Sommer, Stacy; Berndt, Theresa; Craig, Theodore; Kumar, Rajiv

    2007-03-01

    Phosphate homeostasis is preserved during variations in phosphate intake by short-term intrinsic renal and intestinal adaptations in transport processes, and by more long-term hormonal mechanisms, which regulate the efficiency of phosphate transport in the kidney and intestine. Recently, several phosphaturic peptides such as fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein-4 (sFRP-4), extracellular phosphoglycoprotein (MEPE) and fibroblast growth factor 7 (FGF-7) have been shown to play a pathogenic role in several hypophosphatemic disorders such as tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), the McCune-Albright syndrome (MAS) and fibrous dysplasia (FD). These proteins induce phosphaturia and hypophosphatemia in vivo, and inhibit sodium-dependent renal phosphate transport in cultured renal epithelial cells. Interestingly, despite the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25-dihydroxyvitamin D (1alpha,25(OH)(2)D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1alpha-hydroxylase activity. In FGF-23 knockout mice, 25-hydroxyvitamin D 1alpha-hydroxylase expression is increased and elevated serum 1alpha,25(OH)(2)D levels cause significant hypercalcemia and hyperphosphatemia. MEPE, however, increases circulating 1alpha,25(OH)(2)D. Circulating or local concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1alpha-hydroxylase activity in renal tissues under physiologic circumstances. PMID:17224271

  18. Molecular cytogenetic diagnosis of Williams syndrome

    SciTech Connect

    Hirota, Hamao; Matsuoka, Rumiko; Kimura, Misa

    1996-08-23

    Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives. 22 refs., 4 figs., 1 tab.

  19. Nephrolithiasis and Nephrocalcinosis in Children - Metabolic and Genetic Factors.

    PubMed

    Tasic, Velibor; Gucev, Zoran

    2015-09-01

    Diagnosis and management of pediatric nephrolithiasis/nephrocalcinosis is a very complex and challenging task for every pediatrician. It is based on correct. disease history taking, which may guide to the mode of inheritance (dominant, recessive, x-linked). Ethnicity and consanguinity should also be investigated since they predispose to high prevalence of certain disorders. One should always begin with cheap and available screening tests. Herein we will review clinical, biochemical, metabolic and genetic characteristics of the inherited diseases which lead to nephrolithiasis/nephrocalcinosis, such as: idiopathic hypercalciuria, renal hypophosphatemia, renal tubular acidosis, idiopathic infantile hypercalcemia, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypocitraturia, cystinuria, primary hyperoxaluria and renal hypouricemia. Modern genetic techniques such as next generation sequencing enable nowadays diagnosis of rare disease using only a blood sample, trough massive parallel resequencing of many genes. This is very helpful for anuric patients or on dialysis where blood and urine biochemistry are not informative. Genetic testing also replaces invasive liver biopsy or unpleasant acidification tests and enables prenatal or early postnatal diagnosis. PMID:26540764

  20. An Unusual Cause of Altered Mental Status in Multiple Myeloma: An Extraosseous Manifestation

    PubMed Central

    Spanuchart, Ittikorn; O-charoen, Pichaya; Kitamura, Christian; Sumida, Lauren; Roytman, Marina

    2016-01-01

    Multiple myeloma typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Extraosseous manifestations are rare. We report on a patient who was recently diagnosed with multiple myeloma and completed the first cycle of bortezomib, dexamethasone, and palliative radiation therapy with good response. Two weeks after discharge, she became confused and was re-admitted. Despite treatment with lactulose and rifaximin, altered mental status worsened. Computer tomographic scan of abdomen showed hepatomegaly and numerous ill-defined small hyperdense nodules scattered throughout the liver. Liver biopsy demonstrated aggregation of plasma cell myeloma. Magnetic resonance imaging of brain revealed dural thickening. Patient's altered mental status was likely from leptomeningeal myelomatosis and hyperammonemic encephalopathy. Although extraosseous manifestations in multiple myeloma including liver and leptomeningeal involvement are rare, its incidence has increased. This condition portends a poor prognosis. The non-specific manifestations of extraosseous myeloma can be confused with complications of multiple sclerosis and lead to incorrect management, thus clinicians should be aware of these pathologies and perform proper diagnostic tests including imaging and tissue pathology. The most effective treatment is unknown, however bortezomib and thalidomide show promise. PMID:27099806

  1. 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.

  2. Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84), in the treatment of postmenopausal osteoporosis

    PubMed Central

    Pietrogrande, Luca

    2010-01-01

    Full length (1-84) parathyroid hormone (PTH) was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84) in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD) was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation. PMID:21072288

  3. Micronutrients and the premenstrual syndrome: the case for calcium.

    PubMed

    Thys-Jacobs, S

    2000-04-01

    Premenstrual syndrome afflicts millions of premenopausal women and has been described as one of the most common disorders in women. Research over the past few years suggests that a variety of nutrients may have an important role in the phase related mood and behavioral disturbances of the premenstrual syndrome. There is scientific evidence, at least for a few of these micronutrients, specifically calcium and vitamin D, supporting cyclic fluctuations during the menstrual cycle that may help explain some features of PMS. Ovarian hormones influence calcium, magnesium and vitamin D metabolism. Estrogen regulates calcium metabolism, intestinal calcium absorption and parathyroid gene expression and secretion, triggering fluctuations across the menstrual cycle. Alterations in calcium homeostasis (hypocalcemia and hypercalcemia) have long been associated with many affective disturbances. PMS shares many features of depression, anxiety and the dysphoric states. The similarity between the symptoms of PMS and hypocalcemia is remarkable. Clinical trials in women with PMS have found that calcium supplementation effectively alleviates the majority of mood and somatic symptoms. Evidence to date indicates that women with luteal phase symptomatology have an underlying calcium dysregulation with a secondary hyperparathyroidism and vitamin D deficiency. This strongly suggests that PMS represents the clinical manifestation of a calcium deficiency state that is unmasked following the rise of ovarian steroid hormone concentrations during the menstrual cycle. PMID:10763903

  4. A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye.

    PubMed

    Varım, Ceyhun; Ergenc, Hasan; Uyanık, Mehmet Sevki; Kaya, Tezcan; Nalbant, Ahmet; Karacaer, Cengiz; Sunu, Cenk; Tamer, Ali

    2015-09-15

    Multiple myeloma (MM), the second most common hematological malignancy, is caused by the accumulation of monoclonal plasma cells in bone marrow. It accounts for 10-15% of deaths from hematological malignancies and approximately 2% of deaths from cancer. The median age at presentation is 70 years old. The diagnosis is incidental in 30% of cases. MM is often discovered through routine blood screening with a large gap between the total protein and the albumin levels. Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye). Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR) to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma. PMID:27275266

  5. Prevalence of scoliosis in Williams-Beuren syndrome patients treated at a regional reference center

    PubMed Central

    Damasceno, Marcelo Loquette; Cristante, Alexandre Fogaça; Marcon, Raphael Martus; de Barros Filho, Tarcísio Eloy Pessoa

    2014-01-01

    OBJECTIVE: This study assessed the prevalence of scoliosis and the patterns of scoliotic curves in patients with Williams-Beuren syndrome. Williams-Beuren syndrome is caused by a chromosome 7q11.23 deletion in a region containing 28 genes, with the gene encoding elastin situated approximately at the midpoint of the deletion. Mutation of the elastin gene leads to phenotypic changes in patients, including neurodevelopmental impairment of varying degrees, characteristic facies, cardiovascular abnormalities, hypercalcemia, urological dysfunctions, and bone and joint dysfunctions. METHODS: A total of 41 patients diagnosed with Williams-Beuren syndrome, who were followed up at the genetics ambulatory center of a large referral hospital, were included in the study. There were 25 male subjects. The patients were examined and submitted to radiographic investigation for Cobb angle calculation. RESULTS: It was observed that 14 patients had scoliosis; of these 14 patients, 10 were male. The pattern of deformity in younger patients was that of flexible and simple curves, although adults presented with double and triple curves. Statistical analysis showed no relationships between scoliosis and age or sex. CONCLUSION: This study revealed a prevalence of scoliosis in patients with Williams-Beuren syndrome of 34.1%; however, age and sex were not significantly associated with scoliosis or with the severity of the curves. PMID:25029575

  6. Contemporary management of phosphorus retention in chronic kidney disease: a review.

    PubMed

    Amiri, Fateme Shamekhi

    2015-12-01

    Hyperphosphatemia is the most common metabolic complications of end-stage kidney disease (ESKD). Large observational studies have identified hyperphosphatemia as an independent risk factor for cardiovascular disease and mortality in dialysis patients and subsequent studies found that subtle increases in serum phosphate levels even within the normal range are also associated with increased risk for death in predialysis and non-kidney disease population. On the basis of these results, current national practice guidelines advocate more aggressive treatment of hyperphosphatemia to lower serum phosphate targets than in the past . Treatment of hyperphosphatemia requires to strict management through dietary restriction, oral phosphate binders, and dialysis. Calcium-based phosphate binders have low cost and widespread use but cause vascular calcification and hypercalcemia. Non-calcium-based phosphate binders are effective but expensive. Bixalomer is a new Ca-free, metal-free, potent phosphate binder, non-hydrochloride, and non-absorptive polymer, which improves metabolic acidosis. FGF-23 appears as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients. This review focuses on novel therapeutic approaches dealing with hyperphosphatemia in chronic kidney disease. PMID:26032778

  7. [Infectious pleurisy as first sign of multiple myeloma in a young 28 years old].

    PubMed

    Benali, A; Kahouli, S; El Ouazzani, H; Souhi, H; Abderrahmani Rhorfi, I; Abid, A; Yahyaoui, A; Zahid, H; Messaoudi, N

    2015-10-01

    Multiple myeloma is a malignant proliferation of plasma cells, mainly affecting the bone marrow. It rarely occurs in young patients. The medical observation study reveals multiple myeloma discovered through a purulent pleurisy in a 28-year-old subject. This patient was admitted to the pneumology service of the Mohamed V military hospital in Rabat for a fever and dyspnea evolving into a context of poor general condition. Clinical examination found a right pleural fluid effusion syndrome. The pleural puncture reveals a germ-free exudative purulent fluid without plasma cells. The myeloma diagnosis was suspected due to the combination of an aplastic normochromic normocytic anemia at 4.5g/dL of hemoglobin, an accelerated erythrocyte sedimentation rate, hypercalcemia, renal failure and osteolytic lesions located mainly in the skull and pelvis area, oriented by electrophoresis and serum protein immunosubstraction revealing a narrow peak in monoclonal beta-2 globulin at 70.56g/L with a lambda monoclonal gammopathy with immunoglobulin G, and confirmed by the myelogram showing a 74% rate of bone marrow plasma cells. The occurrence of myeloma at a young age is rare and the purulent pleurisy without plasma cells is a rare form of presentation and represents a poor prognosis. PMID:25727663

  8. Primary hypoadrenocorticism in ten cats.

    PubMed

    Peterson, M E; Greco, D S; Orth, D N

    1989-01-01

    Primary hypoadrenocorticism was diagnosed in ten young to middle-aged cats of mixed breeding. Five of the cats were male, and five were female. Historic signs included lethargy (n = 10), anorexia (n = 10), weight loss (n = 9), vomiting (n = 4), and polyuria (n = 3). Dehydration (n = 9), hypothermia (n = 8), prolonged capillary refill time (n = 5), weak pulse (n = 5), collapse (n = 3), and sinus bradycardia (n = 2) were found on physical examination. Results of initial laboratory tests revealed anemia (n = 3), absolute lymphocytosis (n = 2), absolute eosinophilia (n = 1), and azotemia and hyperphosphatemia (n = 10). Serum electrolyte changes included hyponatremia (n = 10), hyperkalemia (n = 9), hypochloremia (n = 9), and hypercalcemia (n = 1). The diagnosis of primary adrenocortical insufficiency was established on the basis of results of adrenocorticotropic hormone (ACTH) stimulation tests (n = 10) and endogenous plasma ACTH determinations (n = 7). Initial therapy for hypoadrenocorticism included intravenous administration of 0.9% saline and dexamethasone and intramuscular administration of desoxycorticosterone acetate in oil. Three cats were euthanatized shortly after diagnosis because of poor clinical response. Results of necropsy examination were unremarkable except for complete destruction of both adrenal cortices. Seven cats were treated chronically with oral prednisone or intramuscular methylprednisolone acetate for glucocorticoid supplementation and with oral fludrocortisone acetate or intramuscular injections of repository desoxycorticosterone pivalate for mineralocorticoid replacement. One cat died after 47 days of therapy from unknown causes; the other six cats are still alive and well after 3 to 70 months of treatment. PMID:2469793

  9. The Endemic Mimic: Blastomycosis An Illness Often Misdiagnosed

    PubMed Central

    Bradsher, Robert W.

    2014-01-01

    One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region. PMID:25125734

  10. Three-year financial analysis of minimally invasive radio-guided parathyroidectomy.

    PubMed

    Hutchinson, Julie R; Yandell, David W; Bumpous, Jeffrey M; Fleming, Muffin M; Flynn, Michael B

    2004-12-01

    Minimally invasive radio-guided parathyroidectomy (MIRP) has had a high success rate in correcting hypercalcemia, along with a low morbidity rate and high patient satisfaction. Our study was conducted in an attempt to analyze the cost-effectiveness of MIRP in patients treated for primary hyperparathyroidism. We conducted a retrospective study of the total charges of three groups of patients undergoing surgery for previously untreated hyperparathyroidism in a single health care system. The three study groups included patients undergoing traditional bilateral neck exploration, MIRP, and neck exploration guided by intraoperative parathormone (PTH) assay. Charges were stratified into preoperative, intraoperative, and postoperative categories. The average total charge was $8,512 for MIRP, $12,723 for traditional neck exploration, and $13,011 for bilateral neck exploration with PTH assay. The decreased charge for MIRP was due to reduced operating room time, anesthesia costs, length of hospitalization, and an avoidance of the use of intraoperative tissue analysis and PTH assay. There was a greater than $4,000 savings with MIRP as compared with the more extensive neck exploration. These savings more than compensate for the cost of technology (preoperative sestamibi scan and intraoperative gamma probe) necessary to perform radio-guided parathyroidectomy. PMID:15663056

  11. Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T-cell lymphoma.

    PubMed

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  12. Waldenström's macroglobulinemia in a dog with a bleeding diathesis.

    PubMed

    Jaillardon, Laetitia; Fournel-Fleury, Corinne

    2011-09-01

    An 11-year-old female spayed Whippet dog was referred to the Veterinary Hospital of the National Veterinary School of Lyon with a 3-month history of chronic bleeding, cutaneous masses suggestive of hematomas, and hemorrhagic diarrhea. Laboratory abnormalities included leukopenia with neutropenia and lymphopenia, rouleaux formation, marked hyperproteinemia with hyperglobulinemia and normoalbuminemia, hypercalcemia, markedly increased serum urea concentration, mildly increased creatinine concentration, and proteinuria. Hemostatic screening tests showed marked prolongation of thrombin time, increased concentrations of fibrin(ogen) degradation products and D-dimers, and slightly prolonged activated partial thromboplastin time. Serum and urine protein electrophoresis revealed a monoclonal peak identified as IgM by immunoelectrophoresis and an M-spike, respectively. Cytologic evaluation of bone marrow revealed a hypocellular sample with lymphoplasmacytic cells comprising approximately 50% of all nucleated cells. These findings were consistent with a diagnosis of Waldenström's macroglobulinemia with secondary bleeding diathesis. Treatment with prednisone and chlorambucil was initiated, and the dog had a good response. PMID:21827519

  13. Intravenous pamidronate: infusion rate and safety.

    PubMed

    Tyrrell, C J; Collinson, M; Madsen, E L; Ford, J M; Coleman, T

    1994-01-01

    In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D-glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2-microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function. PMID:7873459

  14. The Kidney Is the Principal Organ Mediating Klotho Effects

    PubMed Central

    Lindberg, Karolina; Amin, Risul; Moe, Orson W.; Hu, Ming-Chang; Erben, Reinhold G.; Östman Wernerson, Annika; Lanske, Beate; Olauson, Hannes

    2014-01-01

    Klotho was discovered as an antiaging gene, and α-Klotho (Klotho) is expressed in multiple tissues with a broad set of biologic functions. Membrane-bound Klotho binds fibroblast growth factor 23 (FGF23), but a soluble form of Klotho is also produced by alternative splicing or cleavage of the extracellular domain of the membrane-bound protein. The relative organ-specific contributions to the levels and effects of circulating Klotho remain unknown. We explored these issues by generating a novel mouse strain with Klotho deleted throughout the nephron (Six2-KL−/−). Klotho shedding from Six2-KL−/− kidney explants was undetectable and the serum Klotho level was reduced by approximately 80% in Six2-KL−/− mice compared with wild-type littermates. Six2-KL−/− mice exhibited severe growth retardation, kyphosis, and premature death, closely resembling the phenotype of systemic Klotho knockout mice. Notable biochemical changes included hyperphosphatemia, hypercalcemia, hyperaldosteronism, and elevated levels of 1,25-dihydroxyvitamin D and Fgf23, consistent with disrupted renal Fgf23 signaling. Kidney histology demonstrated interstitial fibrosis and nephrocalcinosis in addition to absent dimorphic tubules. A direct comparative analysis between Six2-KL−/− and systemic Klotho knockout mice supports extensive, yet indistinguishable, extrarenal organ manifestations. Thus, our data reveal the kidney as the principal contributor of circulating Klotho and Klotho-induced antiaging traits. PMID:24854271

  15. Bone Metastasis from Renal Cell Carcinoma

    PubMed Central

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  16. Solanum malacoxylon: a toxic plant which affects animal calcium metabolism.

    PubMed

    Boland, R L

    1988-12-01

    The "enteque seco" is a disease of calcinosis, i.e., pathological deposition of calcium phosphate in soft tissues, which occurs in grazing cattle in Argentina and is of considerable economic importance. The ingestion of leaves of Solanum malacoxylon has been identified as the cause of the disease. Hypercalcemia and/or hyperphosphatemia and mineralization of the cardiovascular and pulmonary systems are usually seen in bovines or experimental animals exposed to this plant. The symptoms of the disease resemble those of vitamin D intoxication. In agreement with these observations, a glycoside derivative of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D in animals, has been identified as the toxic principle of S. malacoxylon. Glycoside conjugates of its precursors, 25-hydroxyvitamin D3 and vitamin D3, may also be present. Recent studies indicate that the plant factor is modified in the rumen of bovines through cleavage of the glycosidic linkage and further conversion of the released 1,25(OH)2D3 to a more polar metabolite, possibly 1,24,25-trihydroxyvitamin D3. Excess free 1,25(OH)2D3 may alter extracellular and intracellular Ca homeostasis in intoxicated animals through a receptor-mediated mechanism and activation of membrane Ca channels. In addition, 1,24,25(OH)3D3 may potentiate the effects of 1,25(OH)2D3 on intestinal Ca transport. PMID:3077267

  17. Vitamin D3 toxicity in dairy cows.

    PubMed

    Littledike, E T; Horst, R L

    1982-05-01

    Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum. PMID:6286738

  18. Changes in bone structure and metabolism during simulated weightlessness: Endocrine and dietary factors

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Wronski, T. J.

    1985-01-01

    The role of vitamin D, PTH and corticosterone in the skeletal alterations induced by simulated weightlessness was examined. The first objective was to determine if changes in the serum concentrations of Ca, P sub i, osteocalcin, 25-OH-D, 24,25(OH)2D or 1,25(OH)2D also occur following acute skeletal unloading. Animals were either suspended or pair fed for 2, 5, 7, 10, 12 and 15 days and the serum concentrations of Ca, P sub i, osteocalcin and the vitamin D metabolites measured. Bone histology was examined at day 5 after suspension. Acute skeletal unloading produced a transient hypercalcemia, a significant fall in serum osteocalcin and serum 1,25(OH)2D, a slight rise in serum 24,25(OH)2D, but did not affect the serum concentrations of P sub i or 25-OH-D. At the nadir in serum 1,25(OH)2D serum osteocalcin was reduced by 22%, osteoblast surface by 32% and longitudinal bone growth by 21%.

  19. How I treat plasma cell leukemia.

    PubMed

    van de Donk, Niels W C J; Lokhorst, Henk M; Anderson, Kenneth C; Richardson, Paul G

    2012-09-20

    Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum β(2)-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients. PMID:22837533

  20. Evaluation of efficacy, safety and tolerability of high dose-intermittent calcitriol supplementation to advanced intrahepatic cholangiocarcinoma patients--a pilot study.

    PubMed

    Sookprasert, Aumkhae; Pugkhem, Ake; Khuntikeo, Narong; Chur-in, Siri; Chamadol, Nittaya; Prawan, Auemduan; Janeklang, Somkid; Vaeteewoottacharn, Kulthida; Kukongviriyapan, Veerapol; Pairojkul, Chawalit; Bhudhisawasdi, Vajarabhongsa; Wongkham, Sopit

    2012-01-01

    Antitumor activity (growth suppression) of vitamin D has been demonstrated using cholangiocarcinoma (CCA) cell lines, CCA cell-grafted animal models, and human CCA tissue cultures. The present study aimed to determine the toxicity and tolerability of intermittent-high dose calcitriol in advanced inoperable intrahepatic CCA patients and to evaluate the therapeutic efficacy of combinations of calcitriol and 5-fluorouracil-based chemotherapeutic drugs. The patients were divided into 3 groups: the first (n=2) received intermittent-high dose oral calcitriol 12 μg/day for 3 days, i.e. Monday-Wednesday, per week up to 3 months. The treatment did not cause any serious adverse events, except hypercalcemia grade I, once in 72 administrations. The second group (n=3) received chemotherapeutic drugs (5-fluorouracil, Mitomycin C and Leucovorin) for 3 cycles, one patient showing a partial response. The third group (n=4) received high dose calcitriol in combination with chemotherapeutic-drugs. All 4 patients encountered serious adverse events and two of them were withdrawn after the first drug cycle. This pilot study suggests that, although high dose-intermittent calcitriol appeared to be safe and tolerated well in advanced intrahepatic CCA patients, co-administration with 5-fluorouracil-based chemotherapeutic drugs caused unexpected potentiation of their toxicity. Adjustment of the doses of both drugs is required to avoid such toxicity and to optimize therapeutic efficacy of anticancer drugs when they were combined with high dose-intermittent calcitriol. PMID:23480759

  1. 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

  2. Atypical Parathyroid Adenoma Complicated with Protracted Hungry Bone Syndrome after Surgery: A Case Report and Literature Review

    PubMed Central

    Juárez-León, Óscar Alfredo; Gómez-Sámano, Miguel Ángel; Cuevas-Ramos, Daniel; Almeda-Valdés, Paloma; López-Flores A La Torre, Manuel Alejandro; Reza-Albarrán, Alfredo Adolfo; Gómez-Pérez, Francisco Javier

    2015-01-01

    Hungry Bone Syndrome refers to the severe and prolonged hypocalcemia and hypophosphatemia, following parathyroidectomy in patients with hyperparathyroidism. We present the case of an eighteen-year-old woman with a four-year history of hyporexia, polydipsia, weight loss, growth retardation, and poor academic performance. The diagnostic work-up demonstrated primary hyperparathyroidism with hypercalcemia of 13.36 mg/dL, a PTH level of 2551 pg/mL, bone brown tumors, and microcalcifications within pancreas and kidneys. Neck ultrasonography revealed a parathyroid adenoma of 33 × 14 × 14 mm, also identified on 99Tc-sestamibi scan. Bone densitometry showed decreased Z-Score values (total lumbar Z-Score of −4.2). A right hemithyroidectomy and right lower parathyroidectomy were performed. Pathological examination showed an atypical parathyroid adenoma, of 3.8 g of weight and 2.8 cm in diameter. After surgery she developed hypocalcemia with tetany and QTc interval prolongation. The patient required 3 months of oral and intravenous calcium supplementation due to Hungry Bone Syndrome (HBS). After 42 months, she is still under oral calcium. Usually HBS lasts less than 12 months. Therefore we propose the term “Protracted HBS” in patients with particularly long recovery of 1 year. We present a literature review of the diagnosis, pathophysiology, and treatment of HBS. PMID:26640724

  3. Vitamin D metabolites and/or analogs: which D for which patient?

    PubMed

    Mazzaferro, S; Goldsmith, D; Larsson, T E; Massy, Z A; Cozzolino, M

    2014-03-01

    Numerous drugs with vitamin D activity are available for clinical use and it may not be easy for the nonspecialist to select the most suitable for the individual patient. In this paper we review the main characteristics of the available drugs and provide evidence about any potential specific clinical indications, with special emphasis on renal patients, in order to facilitate the optimal choice. Natural vitamin D products (i.e. those identical to natural metabolites) are first examined, followed by the most frequently used synthetic molecules (i.e. bioengineered molecules not-existing in nature), which are generally indicated as " analogs". Either cholecalciferol, ergocalciferol or calcifediol can be employed in subjects with normal renal function and in CKD stage 3-5 patients to correct vitamin D deficiency and improve, respectively, age- or growth-related bone disease and secondary hyperparathyroidism. Calcifediol can be considered more rapid and effective. In all cases, especially with increasing doses, the risk of hypercalcemia must be taken into account. Calcitriol, which can be regarded as the active hormonal form of vitamin D, has the most potent hypercalcemic effect in both normal and renal failure patients. In renal patients calcitriol is a potent inhibitor of parathyroid activity, but the risk of hypercalcemia, now regarded as harmful, is evident whenever pharmacologic doses are used. Alfacalcidol, requiring 25-hydroxylation to become the active hormonal form of vitamin D3, is prescribed in normal subjects to treat osteoporosis and in renal patients to cure hyperparathyroidism and renal bone disease. Doxercalciferol, transformed into the active hormonal form of vitamin D2 following 25-hydroxylation, is mostly studied in renal patients in whom it cures secondary hyperparathyroidism, possibly with a lower calcemic effect than calcitriol. Paricalcitol, a vitamin D2 analog not requiring activation, has been specifically developed to suppress PTH in renal

  4. Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study

    PubMed Central

    Marston, Louise; Walters, Kate; Geddes, John R.; King, Michael; Osborn, David P. J.

    2016-01-01

    Background There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine. Methods and Findings We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64–3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45–0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45–0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47–0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40–0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29–0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09–0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13–0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10–0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14–0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07

  5. Outcome of patients with multiple myeloma and renal failure on novel regimens.

    PubMed

    Soleymanian, Tayebeh; Soleimani, Adel; Musavi, Asadollah; Mojtahedi, Kourosh; Hamid, Gholamreza

    2016-03-01

    Renal involvement occurs in 20-40% of newly diagnosed multiple myeloma (MM) patients, and diagnosis of myeloma is frequently made after investigation for unexplained renal disease. This is a retrospective study between 2006 and 2013 in which 57 consecutive patients seen at the Nephrology Unit with diagnosis of MM were enrolled. MM was diagnosed for the first time because of renal dysfunction and/or proteinuria in these patients. The mean age of the patients (65% male) was 58.3 ± 12.7 years. The median baseline serum creatinine was 3.5 mg/dL (1.4-14.5). Anemia (hemoglobin <12 g/dL) was noted in 88% and hypercalcemia (calcium >10.5 mg/dL) in 35% of patients. Early hemodialysis was started in 28 patients (49%). Thalidomide plus dexamethasone (16% on bortezomib) were the main therapeutic regimens. Three patients (5%) underwent autologous stem cell transplantation. Twenty-six patients (45.6%) died during a median follow-up of 25 months (1-90). The mean age of patients who died was significantly higher than the age in patients who were alive (62.2 ± 12.7 vs. 55.2 ± 11.9 years, respectively; P = 0.037). Early hemodialysis had no significant effect on mortality rate. The one-, three and five year patient survival was 71%, 54%, and 41%, respectively. The median overall survival of patients was 50 months. Prolonged patient survival can be expected in myeloma patients with renal failure or on dialysis by applying novel therapeutic agents. PMID:26997388

  6. Therapy of Hypoparathyroidism with PTH(1–84): A Prospective Four-Year Investigation of Efficacy and Safety

    PubMed Central

    Cusano, Natalie E.; Rubin, Mishaela R.; McMahon, Donald J.; Zhang, Chiyuan; Ives, Rebecca; Tulley, Amanda; Sliney, James; Cremers, Serge C.

    2013-01-01

    Context: PTH may be an effective treatment option for hypoparathyroidism, but long-term data are not available. Objective: We studied the effect of 4 yr of PTH(1–84) treatment in hypoparathyroidism. Design: Twenty-seven subjects were treated with PTH(1–84) for 4 yr, with prospective monitoring of calcium and vitamin D requirements, serum and urinary calcium, serum phosphorus, bone turnover markers, and bone mineral density (BMD). Results: Treatment with PTH(1–84) reduced supplemental calcium requirements by 37% (P = 0.006) and 1,25-dihydroxyvitamin D requirements by 45% (P = 0.008). Seven subjects (26%) were able to stop 1,25-dihydroxyvitamin D completely. Serum calcium concentration remained stable, and urinary calcium and phosphorus excretion fell. Lumbar spine BMD increased by 5.5 ± 9% at 4 yr (P < 0.0001). Femoral neck and total hip BMD remained stable. At 4 yr, distal radius BMD was not different from baseline. Bone turnover markers increased significantly, reaching a 3-fold peak from baseline values at 6–12 months (P < 0.05 for all), subsequently declining to steady-state levels at 30 months. Hypercalcemia was uncommon (11 episodes in eight subjects over 4 yr; 1.9% of all values), with most episodes occurring within the first 6 months and resolving with adjustment of supplemental calcium and vitamin D. Conclusions: PTH(1–84) treatment of hypoparathyroidism for up to 4 yr maintains the serum calcium concentration, while significantly reducing supplemental calcium and 1,25-dihydroxyvitamin D requirements. Lumbar spine BMD increases without significant changes at other sites. These data provide support for the safety and efficacy of PTH(1–84) therapy in hypoparathyroidism for up to 4 yr. PMID:23162103

  7. Canine lymphoma: a review.

    PubMed

    Zandvliet, M

    2016-06-01

    Canine lymphoma (cL) is a common type of neoplasia in dogs with an estimated incidence rate of 20-100 cases per 100,000 dogs and is in many respects comparable to non-Hodgkin lymphoma in humans. Although the exact cause is unknown, environmental factors and genetic susceptibility are thought to play an important role. cL is not a single disease, and a wide variation in clinical presentations and histological subtypes is recognized. Despite this potential variation, most dogs present with generalized lymphadenopathy (multicentric form) and intermediate to high-grade lymphoma, more commonly of B-cell origin. The most common paraneoplastic sign is hypercalcemia that is associated with the T-cell immunophenotype. Chemotherapy is the treatment of choice and a doxorubicin-based multidrug protocol is currently the standard of care. A complete remission is obtained for most dogs and lasts for a median period of 7-10 months, resulting in a median survival of 10-14 months. Many prognostic factors have been reported, but stage, immunophenotype, tumor grade, and response to chemotherapy appear of particular importance. Failure to respond to chemotherapy suggests drug resistance, which can be partly attributed to the expression of drug transporters of the ABC-transporter superfamily, including P-gp and BCRP. Ultimately, most lymphomas will become drug resistant and the development of treatments aimed at reversing drug resistance or alternative treatment modalities (e.g. immunotherapy and targeted therapy) are of major importance. This review aims to summarize the relevant data on cL, as well as to provide an update of the recent literature. PMID:26953614

  8. Study of Primary Hyperparathyroidism

    PubMed Central

    Girish, Parmar; Lala, M.; Chadha, M.; Shah, N. F.; Chauhan, P. H.

    2012-01-01

    Introduction: The clinical spectrum of primary hyperparathyroidism (PHPT) has undergone a striking change with asymptomatic form predominant in developed countries, whereas symptomatic form predominant in developing countries. In this study, we have analyzed clinical presentation, investigations, management, operative findings in patients with PHPT at our center. Materials and Method: A retrospective, review of medical records of all patients with PHPT between 2000 and July 2012 at our institute was undertaken. A total of 96 patients were included in this study. Results: The mean age of patients was 50.8 years. Of the 96 patients, 63 were females (65.6%) and 33 were males (34.4%). Among them, 17.7% were asymptomatic and 82.3% were symptomatic. Bone pain was the most common complaint (52%) followed by renal stones (27%). Nearly 10.4% were part of familial PHPT, whereas others were sporadic adenomas. All patients had hypercalcemia (range 10.5–19.4 mg/dl) with elevated parathyroid (PTH) levels (range 32–3820 pg/ml). 25(OH) VitD levels were available in 86 patients (89.6%). There was no correlation between VitaminD levels and symptomatology. Sestamibi scan was true positive in 95.6%, false negative 2.2%, and inconclusive in 2.2%. Ultrasonography (USG) results were true positive in 84.2%, false positive in 6.3%, and false negative in 9.5%. Intraoperative PTH levels were measured in 83.3% patients. Postoperative complications were reported in 20.8% patients. Conclusions: Clinical spectrum of PHPT varies but bones and stones are still the predominant manifestations even in affluent society. Asymptomatic form also exists and can be detected by routine measurement of serum calcium. There was no correlation seen between the 25 VitD levels and clinical symptoms. PMID:23565449

  9. Mineral and bone disorder after kidney transplantation

    PubMed Central

    Taweesedt, Pahnwat T; Disthabanchong, Sinee

    2015-01-01

    After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia. PMID:26722650

  10. Villin Promoter-Mediated Transgenic Expression of TRPV6 Increases Intestinal Calcium Absorption in Wild-type and VDR Knockout Mice

    PubMed Central

    Cui, Min; Li, Qiang; Johnson, Robert; Fleet, James C.

    2012-01-01

    Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. Transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was >3 fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal CYP27B1 mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to <10% of WT but small intestine calbindin-D9k expression was elevated >15X in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, and low BMD and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D9K mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR independent up-regulation of intestinal calbindin D9k in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. PMID:22589201

  11. Vitamin D intoxication due to an erroneously manufactured dietary supplement in seven children.

    PubMed

    Kara, Cengiz; Gunindi, Figen; Ustyol, Ala; Aydin, Murat

    2014-01-01

    Pediatric cases of vitamin D intoxication (VDI) with dietary supplements have not been previously reported. We report on 7 children with VDI caused by consumption of a fish oil supplement containing an excessively high dose of vitamin D due to a manufacturing error. Seven children aged between 0.7 and 4.2 years were admitted with symptoms of hypercalcemia. Initial median (range) serum concentrations of calcium and 25-hydroxyvitamin D were 16.5 (13.4-18.8) mg/dL and 620 (340-962) ng/mL, respectively. Repeated questioning of the parents revealed use of a fish oil that was produced recently by a local manufacturer. Analysis of the fish oil by gas chromatography/mass spectrometry revealed that the vitamin D3 content was ~4000 times the labeled concentration. Estimated daily amounts of vitamin D3 intake varied between 266,000 and 800,000 IU. Patients were successfully treated with intravenous hydration, furosemide, and pamidronate infusions. With treatment, serum calcium returned to the normal range within 3 days (range: 2-7 days). Serum 25-hydroxyvitamin D levels normalized within 2 to 3 months. Complications, including nephrocalcinosis, were not observed throughout the 1-year follow-up. In conclusion, errors in manufacturing of dietary supplements may be a cause of VDI in children. Physicians should be aware of this possibility in unexplained VDI cases and repeatedly question the families about dietary supplement use. To prevent the occurrence of such unintentional incidents, manufacturers must always monitor the levels of ingredients of their products and should be rigorously overseen by governmental regulatory agencies, as is done in the pharmaceutical industry. PMID:24298009

  12. Primary hyperparathyroidism

    PubMed Central

    Pallan, Shelley; Khan, Aliya

    2011-01-01

    Abstract Objective To discuss the presentation, diagnosis, and management of primary hyperparathyroidism (PHPT) in family medicine. Quality of evidence MEDLINE was searched from 2002 to 2009 using the terms presentation, diagnosis, and treatment of PHPT. Proceedings and guidelines from the Third International Workshop on Primary Hyperparathyroidism in May 2008 were reviewed in detail. Most studies offered level II and III evidence, although there were a number of single randomized controlled trials on PHPT (level I evidence). References from pertinent papers were also searched for relevant articles. Articles most relevant to family medicine and primary care practitioners are presented. Main message Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients. In the Western world, most patients with PHPT present with nonspecific symptoms such as fatigue, mood disturbances, and cognitive impairments. Diagnosis is established when intact parathyroid hormone levels are elevated or at the high end of the normal range in the setting of elevated total or ionized calcium levels (following exclusion of conditions that can mimic PHPT). Criteria for surgery have recently been modified. Surgery is always a suitable option in those with symptomatic PHPT and no contraindications. Those with contraindications or with asymptomatic PHPT not meeting the criteria for surgery can generally be safely monitored and considered for medical management. This might include treatment with bisphosphonates, hormone replacement therapy, raloxifene, or calcimimetic agents; however, there are currently no fracture data for any of these options. Conclusion The definitive therapy for symptomatic and asymptomatic PHPT is parathyroidectomy. In patients with asymptomatic PHPT not meeting the criteria for surgery, monitoring is safe and medical management designed to target skeletal protection or lower serum calcium is a suitable option. PMID:21321169

  13. Denosumab Treatment for Fibrous Dysplasia

    PubMed Central

    Boyce, AM; Chong, WH; Yao, J; Gafni, RI; Kelly, MH; Chamberlain, CE; Bassim, C; Cherman, N; Ellsworth, M; Kasa-Vubu, JZ; Farley, FA; Molinolo, AA; Bhattacharyya, N; Collins, MT

    2012-01-01

    Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cAMP-regulating protein, Gsα. These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. RANK ligand (RANKL) is a cell surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pre-treatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every three months. Over seven months of treatment he showed marked reduction in pain, bone turnover markers, and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium and calcitriol. Bone turnover markers (BTM) showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTM) with CTX (reflecting osteoclast activity) exceeding pre-treatment levels, and accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as

  14. 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

  15. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    de Groot, Theun; Sinke, Anne P; Kortenoeven, Marleen L A; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F; Deen, Peter M T

    2016-07-01

    To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects. PMID:26574046

  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. Rab1 Small GTP-Binding Protein Regulates Cell Surface Trafficking of the Human Calcium-Sensing Receptor

    PubMed Central

    Zhuang, Xiaolei; Adipietro, Kaylin A.; Datta, Shomik; Northup, John K.; Ray, Kausik

    2010-01-01

    The human calcium-sensing receptor (hCaR) is a family-3/C G-protein-coupled receptor that regulates Ca2+ homeostasis by controlling parathyroid hormone secretion. Here we investigated the role of Rab1, a small GTP-binding protein that specifically regulates protein transport from the endoplasmic reticulum to the Golgi, in cell surface transport of the hCaR. Cell surface expression of hCaR transiently expressed in human embryonic kidney 293 cells was strongly augmented by coexpression of Rab1 and attenuated by disruption of endogenous Rab1 function by expression of the dominant-negative Rab1N124I mutant or depletion of Rab1 with small interfering RNA. Rab1N124I expression also partially attenuated cell surface expression and signaling response to gain-of-function mutants of hCaR with truncated carboxyl-terminal sequences at positions 895 and 903. These carboxyl-tail truncations are similar to a deletion between residues S895 and V1075 found in a patient family causing autosomal dominant hypocalcemia. In addition, coexpression with wild-type Rab1 increased cell surface expression of the loss-of-function missense mutation R185Q, located on the hCaR amino-terminal extracellular ligand-binding domain (ECD), which causes familial hypocalciuric hypercalcemia. Truncated hCaR variants containing either the ECD with the first transmembrane helix or only the ECD also display Rab1-dependent cell surface expression or secretion into the culture medium, respectively. These data reveal a role for Rab1 in hCaR trafficking from the endoplasmic reticulum to the Golgi that regulates receptor cell surface expression and thereby cell signaling responsiveness to extracellular calcium. PMID:20861236

  18. Hypophosphatasia - pathophysiology and treatment

    PubMed Central

    Millán, José Luis; Plotkin, Horacio

    2013-01-01

    English Summary Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) in the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). The disease has been classified according to patient age when the first signs and symptoms manifest; i.e., perinatal, infantile, childhood, adult HPP. Other types include odonto HPP and perinatal benign. Babies with the perinatal/infantile forms of HPP often die with severe rickets and respiratory insufficiency and sometimes hypercalcemia and vitamin B6-responsive seizures. The primary biochemical defect in HPP is a deficiency of TNAP activity that leads to elevated circulating levels of substrates, in particular inorganic pyrophosphate (PPi), a potent calcification inhibitor. To-date, the management of HPP has been essentially symptomatic or orthopedic. However, enzyme replacement therapy with mineral-targeting TNAP (sALP-FcD10, also known as ENB-0040 or asfotase alfa) has shown promising results in a mouse model of HPP (Alpl−/− mice). Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acellular cementum, and enamel defects in this model of severe HPP. Clinical trials using mineral-targeting TNAP in children 3 years of age or younger with life-threatening HPP was associated with healing of the skeletal manifestations of HPP as well as improved respiratory and motor function. Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. Enzyme replacement therapy with asfotase alfa has to-date been successful in patients with life-threatening HPP. PMID:25254037

  19. 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.

  20. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation

    PubMed Central

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-01-01

    ABSTRACT Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

  1. Prodifferentiation Activity of Novel Vitamin D₂ Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells.

    PubMed

    Nachliely, Matan; Sharony, Ehud; Bolla, Narasimha Rao; Kutner, Andrzej; Danilenko, Michael

    2016-01-01

    1α,25-dihydroxyvitamin D₃ (1,25D3) is a powerful differentiation inducer for acute myeloid leukemia (AML) cells. However, 1,25D3 doses required for differentiation of AML cells may cause lethal hypercalcemia in vivo. There is evidence that vitamin D₂ is less toxic than vitamin D₃ in animals. Here, we determined the differentiation effects of novel analogs of 1α,25-dihydroxyvitamin D₂ (1,25D2), PRI-1916 and PRI-1917, in which the extended side chains of their previously reported precursors (PRI-1906 and PRI-1907, respectively) underwent further 24Z (24-cis) modification. Using four human AML cell lines representing different stages of myeloid maturation (KG-1a, HL60, U937, and MOLM-13), we found that the potency of PRI-1916 was slightly higher or equal to that of PRI-1906 while PRI-1917 was significantly less potent than PRI-1907. We also demonstrated that 1,25D2 was a less effective differentiation agent than 1,25D3 in these cell lines. Irrespective of their differentiation potency, all the vitamin D₂ derivatives tested were less potent than 1,25D3 in transactivating the DR3-type vitamin D response elements. However, similar to 1,25D3, both 1,25D2 and its analogs could strongly cooperate with the plant polyphenol carnosic acid in inducing cell differentiation and inhibition of G1-S cell cycle transition. These results indicate that the 24Z modification has contrasting effects on the differentiation ability of PRI-1906 and PRI-1907 and that the addition of a plant polyphenol could result in a similar extent of cell differentiation induced by different vitamin D compounds. The enhanced antileukemic effects of the tested combinations may constitute the basis for the development of novel approaches for differentiation therapy of AML. PMID:27399677

  2. Plasma cell leukemia

    PubMed Central

    Albarracin, Flavio; Fonseca, Rafael

    2014-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

  3. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Verstuyf, Annemieke; Verlinden, Lieve; Carmeliet, Geert

    2016-01-01

    1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease. PMID:26681795

  4. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management.

    PubMed

    Rajkumar, S Vincent

    2016-07-01

    Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Patients with del(17p), t(14;16), and t(14;20) have high-risk multiple myeloma. Patients with t(4;14) translocation and gain(1q) have intermediate-risk. All others are considered standard-risk. Initial treatment consists of bortezomib, lenalidomide, dexamethasone (VRD). In high-risk patients, carfilzomib, lenalidomide, dexamethasone (KRD) is an alternative to VRD. In eligible patients, initial therapy is given for approximately 3-4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT at first relapse. Patients not candidates for transplant are treated with Rd until progression, or alternatively, a triplet regimen such as VRD for approximately 12-18 months. After ASCT, lenalidomide maintenance is considered for standard risk patients especially in those who are not in very good partial response or better, while maintenance with a bortezomib-based regimen is needed for patients with intermediate or high-risk disease. Patients with indolent relapse can be treated with 2-drug or 3-drug combinations. Patients with more aggressive relapse require a triplet regimen or a combination of multiple active agents. Am. J. Hematol. 91:720-734, 2016. © 2016 Wiley Periodicals, Inc. PMID:27291302

  5. The vitamin D analog, MART-10, represses metastasis potential via downregulation of epithelial-mesenchymal transition in pancreatic cancer cells.

    PubMed

    Chiang, Kun-Chun; Yeh, Chun-Nan; Hsu, Jun-Te; Jan, Yi-Yin; Chen, Li-Wei; Kuo, Sheng-Fong; Takano, Masashi; Kittaka, Atsushi; Chen, Tai C; Chen, Wen-Tsung; Pang, Jong-Hwei S; Yeh, Ta-Sen; Juang, Horng-Heng

    2014-11-28

    Pancreatic cancer (PDA) is a devastating disease and there is no effective treatment available at present. To develop new regiments against PDA is urgently needed. Previously we have shown that vitamin D analog, MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), exerted potent antiproliferative effect on PDA in vitro and in vivo without causing hypercalcemia. Since metastasis is the major cause of PDA-related death, we therefore investigate the anti-metastasis effect of MART-10 on PDA. Our results showed that both 1α,25(OH)2D3 and MART-10 repressed migration and invasion of BxPC-3 and PANC cells with MART-10 much more potent than 1α,25(OH)2D3. 1α,25(OH)2D3 and MART-10 inhibited epithelial-mesenchymal transition (EMT) in pancreatic cancer cells through downregulation of Snail, Slug, and Vimentin expression in BxPC-3 and PANC cells. MART-10 further blocked cadherin switch (from E-cadherin to N-cadherin) in BxPC-3 cells. The F-actin synthesis in the cytoplasm of BxPC-3 cells was also repressed by 1α,25(OH)2D3 and MART-10 as determined by immunofluorescence stain. Both 1α,25(OH)2D3 and MART-10 decreased MMP-2 and -9 secretion in BxPC-3 cells as determined by western blot and zymography. Collectively, MART-10 should be deemed as a promising regimen against PDA. PMID:25149065

  6. An overall assessment of circumanal gland adenoma in a terrier mix breed dog

    PubMed Central

    Javanbakht, Javad; Tavassoli, Abbas; Sasani, Farhang; Sabbagh, Atefeh; Hassan, Mehdi Aghamohamad; Samakkhah, Shohreh Alian; Shafiee, Radmehr; Jani, Meysam; Alimohammadi, Samad; Samani, Reza; Barati, Fardin; Ghalee, Vahideh Rahmani

    2013-01-01

    In September 2012, a 10-year-old, intact male, terrier mix breed dog was evaluated because of multiple, 0.5 to 1.2 cm in diameter, round, intradermal nodules around the anus. It had surgery to excise a firm, painful swelling in the left ventrolateral perianal region and the excision part was observed under light microscopy. The mass spreading in to sub acute was of left hind leg out from the ventro-lateral of anus, 1.2 cm×1 cm/ 0 cm×0.5 cm in size and 125 g in weight. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Significant laboratory data demonstrated microcytic anemia (hemoglobin of 6.4 mg/dL) and normal coagulation times. No remarkable abnormalities were found in the complete blood count and an ionized calcium of 1.91 mmol/L (reference range, 1.1-1.3 mmol/L) was confirmed hypercalcemia. On cytologic and histopathologic examinations, evaluation of the aspirate revealed a prominent population of round-to-polygonal nucleated cells arranged as cohesive groups with isolated individual cells. A mild degree of anisocytosis and anisokaryosis was observed. In addition, smaller reserve type cells, with darker cytoplasm and a higher nucleocytoplasmic ratio. The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations, the well-developed stroma surrounding the lobules and hepatoid cells was noted. Ulceration, hemorrhage, necrosis and secondary infection with inflammatory cell infiltrates are common. These cytology and histopathology features are consistent with hepatoid gland adenoma. PMID:23835432

  7. In vitro and in vivo evaluation of combined calcitriol and cisplatin in dogs with spontaneously occurring tumors

    PubMed Central

    Rassnick, Kenneth M.; Muindi, Josephia R.; Johnson, Candace S.; Balkman, Cheryl E.; Ramnath, Nithya; Yu, Wei-Dong; Engler, Kristie L.; Page, Rodney L.; Trump, Donald L.

    2009-01-01

    Purpose Calcitriol potentiates cisplatin-mediated activity in a variety of tumor models. We examine here, the effect of calcitriol and cisplatin pre-clinically and clinically in canine spontaneous tumors through in vitro studies on tumor cells and through a phase I study of calcitriol and cisplatin to identify the maximum-tolerated dosage (MTD) of this combination in dogs with cancer and to characterize the pharmacokinetic disposition of calcitriol in dogs. Methods Canine tumor cells were investigated for calcitriol/cisplatin interactions on proliferation using an MTT assay in a median-dose effect analysis; data were used to derive a combination index (CI). Cisplatin was given at a fixed dosage of 60 mg/m2. Calcitriol was given i.v. and the dosage was escalated in cohorts of three dogs until the MTD was defined. Serum calcitriol concentrations were quantified by radioimmunoassay. Results In vitro, CIs<1.0 were obtained for all combinations of calcitriol/cisplatin examined. The MTD was 3.75 μg/kg calcitriol in combination with cisplatin, and hypercalcemia was the dose-limiting toxicosis. The relationship between calcitriol dosage and either Cmax or AUC was linear. Calcitriol dosages >1.5 μg/kg achieved Cmax ≥ 9.8 ng/mL and dosages >1.0 μg/kg achieved AUC ≥ 45 h ng/mL. Conclusions Calcitriol and cisplatin have synergistic antiproliferative effects on multiple canine tumor cells and high-dosages of i.v. calcitriol in combination with cisplatin can be safely administered to dogs. Cmax and AUC at the MTD 3.75 μg/kg calcitriol exceed concentrations associated with antitumor activity in a murine model, indicating this combination might have significant clinical utility in dogs. PMID:18246349

  8. Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties

    PubMed Central

    2013-01-01

    Background Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines’ levels. Methods In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented. Results 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed. Conclusion Vitamin D supplementation to IFN−β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN−β related FLS. Trial registration ClinicalTrials.gov ID: NCT01005095 PMID:23767916

  9. RADIOGUIDED PARATHYROIDECTOMY FOR TERTIARY HYPERPARATHYROIDISM

    PubMed Central

    Somnay, Yash R.; Weinlander, Eric; Alfhefdi, Amal; Schneider, David; Sippel, Rebecca S.; Chen, Herbert

    2015-01-01

    Background Tertiary hyperparathyroidism (3HPT) is defined as the persistent hyper-production of parathyroid hormone (PTH) and resulting hypercalcemia following renal transplantation. Here, we examine the utility of radioguided parathyroidectomy (RGP) in patients with 3HPT. Materials and Methods We reviewed a prospective surgery database containing 80 3HPT patients who underwent RGP from January 2001 to July 2014 at our institution. We evaluated patient demographics, operative management, radioguided neoprobe utilization and operative outcomes. Data are reported as mean ± SEM. Results The mean age of the patients was 52 ± 1 years, and 46% were male. 69 patients had hyperplasia and received subtotal parathyroidectomy, while 5 patients had double adenomas and 6 patients had single adenomas. The average calcium level among 3HPT patients was 10.8± 0.1 mg/dl preoperatively and 8.7 ± 0.1 mg/dl postoperatively. In vivo radioguided counts normalized to background counts averaged 145 ± 4%, while ex vivo counts normalized to background counts averaged 69 ± 5%. All but one ex vivo count was >20%. Ectopically located glands were successfully localized in 38 patients using the gamma probe. Ex vivo percentage did not correlate with parathyroid gland weight, preoperative PTH or preoperative calcium. Our radioguided approach achieved normocalcemia in 96% of 3HPT patients undergoing radioguided parathyroidectomy; 2 patients developed recurrent disease. Conclusions In this series, all enlarged parathyroid glands were localized and resected using the gamma probe. Thus, RGP reliably localizes adenomatous, hyperplastic and ectopically located glands in patients with 3HPT, resulting in high cure rate following resection. PMID:25770735

  10. Bioactive glass combined with bisphosphonates provides protection against biofilms formed by the periodontal pathogen Aggregatibacter actinomycetemcomitans.

    PubMed

    Hiltunen, Anna K; Skogman, Malena E; Rosenqvist, Kirsi; Juvonen, Helka; Ihalainen, Petri; Peltonen, Jouko; Juppo, Anne; Fallarero, Adyary

    2016-03-30

    Biofilms play a pivotal role in the progression of periodontitis and they can be treated with antiseptics (i.e. chlorhexidine) or antibiotics, but these therapeutic alternatives are unable of ameliorating periodontal alveolar bone loss, which has been, on the other hand, successfully treated with bone-preserving agents. The improved bone formation achieved in animal models by the combination of two such agents: bioactive glass (BAG) and bisphosphonates has attracted the interest for further exploring dental applications. However, the antimicrobial effects that may result from combining them have not been yet investigated. Here, our aim was to explore the anti-biofilm effects that could result from combining BAG with bisphosphonates, particularly in a dental biofilm model. The experiments were performed with an oral cavity single-specie (Aggregatibacter actinomycetemcomitans) biofilm assay, which was optimized in this contribution. Risedronate displayed an intrinsic anti-biofilm effect, and all bisphosphonates, except clodronate, reduced biofilm formation when combined with BAG. In particular, the anti-biofilm activity of risedronate was significantly increased by the combination with BAG. Since it has been proposed that some of the antimicrobial effects of BAG are caused by local pH changes, studies of pH variations were performed to gain a mechanistic understanding. However, the observed anti-biofilm effects could not be explained with lowered pHs. Overall, these results do provide further support for the promising use of bisphosphonate-BAG combinations in dental applications. These findings are particularly relevant for patients undergoing cancer chemotherapy, or osteoporotic patients, which are known to be more vulnerable to periodontitis. In such cases, bisphosphonate treatment could play a double positive effect: local treatment of periodontitis (in combination with BAG) and systemic treatment of osteoporosis, prevention of hypercalcemia and metastases. PMID

  11. The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway

    PubMed Central

    Wang, Zhihui; Zhang, Haitao; Sun, Xiaohan; Ren, Lihong

    2016-01-01

    Asthma is a common worldwide health burden, the prevalence of which is increasing. Recently, the biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3, has been reported to have a protective role in murine asthma; however, the molecular mechanisms by which vitamin D3 attenuates asthma-associated airway injury remain elusive. In the present study, BALB/c mice were sensitized to ovalbumin (OVA) and were administered 100 ng 1,25-dihydroxyvitamin D3 (intraperitoneal injection) 30 min prior to each airway challenge. The inflammatory responses were measured by ELISA, airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was analyzed by Masson staining and periodic acid-Schiff staining, markers of oxidative stress were measured by commercial kits, and the expression levels of α-smooth muscle actin (α-SMA) and the activity of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and the transforming growth factor-β (TGF-β)/Smad signaling pathways were measured by immunohistochemistry and western blotting. The results demonstrated that OVA-induced airway inflammation and immunoglobulin E overexpression were significantly reduced by vitamin D3 treatment. In addition, treatment with vitamin D3 decreased α-SMA expression, collagen deposition and goblet cell hyperplasia, and inhibited TGF-β/Smad signaling in the asthmatic airway. The upregulated levels of malondialdehyde, and the reduced activities of superoxide dismutase and glutathione in OVA-challenged mice were also markedly restored following vitamin D3 treatment. Furthermore, treatment with vitamin D3 enhanced activation of the Nrf2/HO-1 pathway in the airways of asthmatic mice. In conclusion, these findings suggest that vitamin D3 may protect airways from asthmatic damage via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway; however, these protective effects were shown to be accompanied by hypercalcemia. PMID:27484042

  12. Uncoupling of Secretion From Growth in Some Hormone Secretory Tissues

    PubMed Central

    2014-01-01

    Context: Most syndromes with benign primary excess of a hormone show positive coupling of hormone secretion to size or proliferation in the affected hormone secretory tissue. Syndromes that lack this coupling seem rare and have not been examined for unifying features among each other. Evidence Acquisition: Selected clinical and basic features were analyzed from original reports and reviews. We examined indices of excess secretion of a hormone and indices of size of secretory tissue within the following three syndromes, each suggestive of uncoupling between these two indices: familial hypocalciuric hypercalcemia, congenital diazoxide-resistant hyperinsulinism, and congenital primary hyperaldosteronism type III (with G151E mutation of the KCNJ5 gene). Evidence Synthesis: Some unifying features among the three syndromes were different from features present among common tumors secreting the same hormone. The unifying and distinguishing features included: 1) expression of hormone excess as early as the first days of life; 2) normal size of tissue that oversecretes a hormone; 3) diffuse histologic expression in the hormonal tissue; 4) resistance to treatment by subtotal ablation of the hormone-secreting tissue; 5) causation by a germline mutation; 6) low potential of the same mutation to cause a tumor by somatic mutation; and 7) expression of the mutated molecule in a pathway between sensing of a serum metabolite and secretion of hormone regulating that metabolite. Conclusion: Some shared clinical and basic features of uncoupling of secretion from size in a hormonal tissue characterize three uncommon states of hormone excess. These features differ importantly from features of common hormonal neoplasm of that tissue. PMID:25004249

  13. Dimerization and DNA recognition rules of mithramycin and its analogues.

    PubMed

    Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min; Tsodikov, Oleg V; Rohr, Jürgen

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents. PMID:26760230

  14. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis.

    PubMed

    Kang, Yibin

    2016-06-01

    Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis. PMID:27184014

  15. Juvenile Paget’s Disease With Heterozygous Duplication In TNFRSF11A Encoding RANK

    PubMed Central

    Whyte, Michael P.; Tau, Cristina; McAlister, William H.; Zhang, Xiafang; Novack, Deborah V.; Preliasco, Virginia; Santini-Araujo, Eduardo; Mumm, Steven

    2014-01-01

    Mendelian disorders of RANKL/OPG/RANK signaling feature the extremes of aberrant osteoclastogenesis and cause either osteopetrosis or rapid turnover skeletal disease. The patients with autosomal dominant accelerated bone remodeling have familial expansile osteolysis, early-onset Paget’s disease of bone, expansile skeletal hyperphosphatasia, or panostotic expansile bone disease due to heterozygous 18-, 27-, 15-, and 12-bp insertional duplications, respectively, within exon 1 of TNFRSF11A that encodes the signal peptide of RANK. Juvenile Paget’s disease (JPD), an autosomal recessive disorder, manifests extremely fast skeletal remodeling, and is usually caused by loss-of-function mutations within TNFRSF11B that encodes OPG. These disorders are ultra-rare. A 13-year-old Bolivian girl was referred at age 3 years. One femur was congenitally short and curved. Then, both bowed. Deafness at age 2 years involved missing ossicles and eroded cochleas. Teeth often had absorbed roots, broke, and were lost. Radiographs had revealed acquired tubular bone widening, cortical thickening, and coarse trabeculation. Biochemical markers indicated rapid skeletal turnover. Histopathology showed accelerated remodeling with abundant osteoclasts. JPD was diagnosed. Immobilization from a femur fracture caused severe hypercalcemia that responded rapidly to pamidronate treatment followed by bone turnover marker and radiographic improvement. No TNFRSF11B mutation was found. Instead, a unique heterozygous 15-bp insertional tandem duplication (87dup15) within exon 1 of TNFRSF11A predicted the same pentapeptide extension of RANK that causes expansile skeletal hyperphosphatasia (84dup15). Single nucleotide polymorphisms in TNFRSF11A and TNFRSF11B possibly impacted her phenotype. Our findings: i) reveal that JPD can be associated with an activating mutation within TNFRSF11A, ii) expand the range and overlap of phenotypes among the mendelian disorders of RANK activation, and iii) call for mutation

  16. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    PubMed Central

    2016-01-01

    Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis. PMID:27184014

  17. Patients with Active Acromegaly are at High Risk of 25(OH)D Deficiency

    PubMed Central

    Halupczok-Żyła, Jowita; Jawiarczyk-Przybyłowska, Aleksandra; Bolanowski, Marek

    2015-01-01

    Acromegaly is a chronic disease characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Electrolyte disturbances such as hypercalcemia and hyperphosphatemia are reported in patients with this disorder. There is limited data on vitamin D status in subjects with acromegaly. The aim of the study was to determine calcium, inorganic phosphate, magnesium, alkaline phosphatase, and 25(OH)D levels with regard to the activity of the disease. We also studied correlations of 25(OH)D and IGF-1, GH, body mass, body mass index, and age. A study group consisted of 55 acromegalic patients, and was divided into three subgroups: active acromegaly (AA), well-controlled acromegaly (WCA), cured acromegaly (CA). We enrolled 29 healthy subjects to a control group (CG). Vitamin D deficiency was recorded in all AA patients, 13 WCA patients (92.86%), 10 CA patients (62.5%), and 13 controls (54.17%). The highest 25(OH)D levels were found in the CG group and the lowest in the AA group (p = 0.012). The dose of octreotide did not influence serum 25(OH)D levels. A significant positive correlation between IGF-1 and 25(OH)D levels was observed in the AA group (r = 0.58, p = 0.024). Inorganic phosphate levels were the highest in the AA group. In conclusion, active acromegalic patients have lower 25(OH)D levels in comparison with the CG and are at higher risk of vitamin D deficiency. PMID:26082755

  18. [Surgery of primary hyperparathyroidism].

    PubMed

    Horányi, János; Szlávik, Rezso; Duffek, László; Darvas, Katalin; Györke, Tamás; Lakatos, Péter; Miklós, Tóth

    2006-12-10

    Surgery of primary hyperparathyroidism. Primary hyperparathyroidism is usually caused by a single parathyroid adenoma, rarely by multiple adenomas or hyperplasia and in 1-2% of cases by carcinoma. The definitive cure of the disease can be achieved only by surgical means. Unfortunately, only 10% of expected cases based on the number of population are diagnosed in Hungary. The main reason is that the disease has no specific symptoms and it causes only a few cases present with clinical entities such as nephrolithiasis, osteoporosis-osteopenia, pancreatitis, hypertension, peptic ulcer disease, depression, etc. The clue to the diagnosis of primary hyperparathyroidism is usually the laboratory result of hypercalcemia and in order to this aim the measurement of serum Ca would be an obligatory part of routine laboratory investigation in Hungary. The diagnosis of primary hyperparathyroidism rests on the laboratory confirmation of increased serum calcium and inappropriately elevated intact parathyroid hormone concentrations. If surgical intervention is planned, cervical ultrasonography and parathyroid-scintigraphy are indicated for the exact localization of hyperfunctioning parathyroid gland(s). CT and/or MRI are usually not necessary, except in cases of previous neck operation. The operation must be performed by surgeon skilled in parathyroid surgery. The surgical success can be assessed intraoperatively by the use of a gamma probe or by intraoperative measurement of parathyroid hormone concentrations in the serum or in the removed tissue(s). Support of these procedures is recommended. Although many recent publications deal with the minimal invasive methods of parathyroidectomy, the cost-effectiveness of these newer techniques are controversial. PMID:17228513

  19. Immunoglobulin D myeloma--problems with diagnosing and staging (own experience and literature review).

    PubMed

    Kuliszkiewicz-Janus, Małgorzata; Zimny, Anna; Sokolska, Violetta; Saşiadek, Marek; Kuliczkowski, Kazimierz

    2005-07-01

    Immunoglobulin D (IgD) myeloma is a rare disease accounting for about 2% of all myelomas. The distinctive features are the predominant occurrence in males and young patients, short survival time, uncertain appearance of M-component in serum electrophoresis, predominance of lambda light chains, frequent renal impairment, hypercalcemia and amyloidosis. The aim of the present study was to show diagnostic difficulties resulting from a variety of non-specific initial symptoms and laboratory findings as well as to compare the staging system proposed by Durie and Salmon with the new risk grouping by Shimamoto. Case histories of 7 patients were analyzed retrospectively. Five of them were diagnosed as IgD multiple myeloma (IgD MM), 1 as non-secretory IgD myeloma and 1 as solitary bone IgD plasmocytoma that evolved to an IgD MM. All patients were staged according to the Durie and Salmon classification and the new risk grouping by Shimamoto. We report diagnostic problems with IgD myeloma in our patients, with special emphasis on non-specific rheumatoidal and neurological symptoms in 1 case. There was a very good correlation of the Japanese classification with the severity of the disease and the risk of death. In conclusion, the initial symptoms of IgD myeloma can be very misleading. Wide differential diagnosis, including autoimmunological disorders of the connective tissue, is necessary. The new Japanese risk grouping seems to be of greater prognostic significance for IgD myeloma than the Durie and Salmon staging system. PMID:16019554

  20. Strategies to manage low-bone turnover.

    PubMed

    Spasovski, G

    2009-01-01

    A change in paradigm occurred lately whereby not hypocalcemia but hypercalcemia and positive calcium balance were considered negative factors. Namely, the use of calcium- based binders in combination with vitamin D analogues, has been shown to lead to an over-suppression of parathyroid hormone (PTH) and development of low-bone turnover adynamic bone disease (ABD). The changing prevalence of various types of bone diseases from a high to low-bone turnover goes in line with the presence of increased risk for vascular calcification (VC), morbidity and mortality in the dialysis population. The attenuation of the previous great expectations in calcium-based phosphate binders and vitamin D-analogues entailed a new treatment strategy to preserve bone and vascular health. Hence, a new evidence for treatment of ABD with various types of non calcium based binders and low calcium dialysate is presented. Sevelamer treatment has reduced calcium concentration and increased PTH levels, resulting in the improvement of markers of bone turnover, increased bone formation and improved trabecular architecture, providing a slower progression of VC. Data on lanthanum beneficial effect on ABD histology have been demonstrated in long-term clinical studies. Although there is a slow release of lanthanum from its bone deposits after discontinuation of the treatment and no association with aluminium- like bone toxicity, there is still an ongoing scientific debate about its long-term toxic potential. Finally, reducing the number of calcium based binders and low calcium dialysate (1.25 mmol/l) has been reported to have an impact on the evolution towards markers reflecting higher bone turnover. Then, adoption of the non calcium-based binders should be reserved to high risk patients with ABD and progression of vascular calcifications associated with increased morbidity and mortality. PMID:19668299

  1. Phosphate metabolism in chronic kidney disease: from pathophysiology to clinical management.

    PubMed

    Spasovski, Goce; Massy, Ziad; Vanholder, Raymond

    2009-01-01

    Hyperphosphatemia is considered as an independent risk factor for surrogate clinical endpoints like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. To date, various treatment options for phosphate removal or reduction are available. The great expectations put into calcium-based phosphate binders were mitigated because of their possible contribution to progressive VC, particularly in patients treated simultaneously with active vitamin D derivatives. Thus, a paradigm change occurred whereby the main clinical concern shifted from the avoidance of hypocalcemia to that of the consequences of inducting a positive calcium balance. Sevelamer-HCl treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia than calcium-based phosphate binders, and a slower progression of VC; however, convincing evidence of improved clinical outcomes in dialysis patients is lacking. Although data on the safety and efficacy of lanthanum carbonate in the treatment of hyperphosphatemia have been provided in long-term clinical studies, there is still an ongoing scientific debate about its possible long-term toxicity. Moreover, there are no data from randomized clinical trials demonstrating beneficial effects of La carbonate treatment on VC or cardiovascular outcomes. In the absence of convincing clinical trials testing the effects of non-metal-based phosphate binders on cardiovascular and global outcomes it appears reasonable to maintain bone health and mineral homeostasis by mainly relying on adaptations of standard therapies. Noncalcium, non-aluminum-based binders might be reserved for patients with major mineral metabolism abnormalities and a high risk of VC. PMID:19708981

  2. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3

    PubMed Central

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S. Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C.; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  3. Evaluation of responses to vitamin D3 (cholecalciferol) in patients on dialysis: a systematic review and meta-analysis.

    PubMed

    Xu, Chen; Li, Yan-Chun; Zhao, Su-Mei; Li, Zhong-Xin

    2016-06-01

    Vitamin D plays a key role in mineral metabolism and its deficiency is often noted in patients on dialysis for end-stage renal disease (ESRD). We evaluated the efficacy and responses to vitamin D3 (cholecalciferol) in patients undergoing dialysis for ESRD. Randomized controlled trials or prospective studies comparing vitamin D3 supplementation to placebo in patients with ESRD on dialysis were searched from medical databases using the terms, 'Calcitriol/Cholecalciferol, vitamin D, chronic kidney disease, hemodialysis, serum calcium, parathyroid hormones (PTH), phosphorus, 25(OH)D, and 1,25(OH)2D'. The outcomes analyzed were serum calcium, PTH, phosphorus, 25(OH)D, and 1,25(OH) 2D levels. Of the 259 records identified, 9 studies with a total of 368 patients were chosen for the current meta-analysis. The number of patients, age, and gender distribution among the groups were comparable. Results reveal a greater increase in both 25(OH)D (Pooled difference in means=0.434, 95% CI 0.174 to 0.694, p=0.001) and 1,25(OH) 2D (Pooled difference in means=0.978, 95% CI 0.615 to 1.34, p<0.001) in the treatment arm, as compared to the placebo. There was no difference in the serum calcium or PTH among the two groups. However, patients in the treatment arm had a significant increase in phosphorus levels (Pooled difference in means=0.434, 95% CI 0.174 to 0.694, p=0.001). Vitamin D supplementation facilitated the maintenance of increased levels of 25(OH) D and 1,25(OH) 2D in patients undergoing dialysis for ESRD. This increase in vitamin D was not associated with hypercalcemia or significant changes in PTH levels. PMID:27076675

  4. A Phase II Trial of a Combination Herbal Supplement for Men with Biochemically Recurrent Prostate Cancer

    PubMed Central

    Dorff, Tanya B.; Groshen, Susan; Tsao-Wei, Denice D.; Xiong, Shigang; Gross, Mitchell E.; Vogelzang, Nicholas; Quinn, David I.; Pinski, Jacek K.

    2014-01-01

    Background Men with biochemical recurrence (BCR) of prostate cancer are typically observed or treated with androgen deprivation therapy. Non-hormonal, non-toxic treatments to slow the rise of PSA are desirable. We studied a combination herbal supplement, Prostate Health Cocktail (PHC), in prostate cancer cell lines and in a population of men with BCR. Methods PC3, LAPC3, and LNCaP cells were incubated with increasing concentrations of PHC suspension. Men previously treated for prostate cancer with surgery, radiation, or both with rising PSA but no radiographic metastases were treated with 3 capsules of PHC daily; the primary endpoint was 50% PSA decline. Circulating tumor cells (CTCs) were identified using parylene membrane filters. Results PHC showed a strong dose-dependent anti-proliferative effect in androgen-sensitive and independent cell lines in vitro and suppression of androgen receptor expression. 40 eligible patients were enrolled in the clinical trial. Median baseline PSA was 2.8 ng/mL (1.1-84.1) and 15 men (38%) had a PSA decline on study (1%-55% reduction) ; 25 (62%) had rising PSA on study. The median duration of PSA stability was 6.4 months. Two patients had grade 2/3 transaminitis; the only other grade 2 toxicities were hyperglycemia, hypercalcemia and flatulence. There were no significant changes in testosterone or dihydrotestosterone. CTCs were identified in 19 men (47%). Conclusion Although the primary endpoint was not met, Prostate Health Cocktail was well tolerated and was associated with PSA declines and stabilization in a significant number of patients. This is the first report of detecting CTCs in men with BCR prostate cancer. Randomized studies are needed to better define the effect of PHC in men with BCR. PMID:25245366

  5. Prodifferentiation Activity of Novel Vitamin D2 Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells

    PubMed Central

    Nachliely, Matan; Sharony, Ehud; Bolla, Narasimha Rao; Kutner, Andrzej; Danilenko, Michael

    2016-01-01

    1α,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation inducer for acute myeloid leukemia (AML) cells. However, 1,25D3 doses required for differentiation of AML cells may cause lethal hypercalcemia in vivo. There is evidence that vitamin D2 is less toxic than vitamin D3 in animals. Here, we determined the differentiation effects of novel analogs of 1α,25-dihydroxyvitamin D2 (1,25D2), PRI-1916 and PRI-1917, in which the extended side chains of their previously reported precursors (PRI-1906 and PRI-1907, respectively) underwent further 24Z (24-cis) modification. Using four human AML cell lines representing different stages of myeloid maturation (KG-1a, HL60, U937, and MOLM-13), we found that the potency of PRI-1916 was slightly higher or equal to that of PRI-1906 while PRI-1917 was significantly less potent than PRI-1907. We also demonstrated that 1,25D2 was a less effective differentiation agent than 1,25D3 in these cell lines. Irrespective of their differentiation potency, all the vitamin D2 derivatives tested were less potent than 1,25D3 in transactivating the DR3-type vitamin D response elements. However, similar to 1,25D3, both 1,25D2 and its analogs could strongly cooperate with the plant polyphenol carnosic acid in inducing cell differentiation and inhibition of G1–S cell cycle transition. These results indicate that the 24Z modification has contrasting effects on the differentiation ability of PRI-1906 and PRI-1907 and that the addition of a plant polyphenol could result in a similar extent of cell differentiation induced by different vitamin D compounds. The enhanced antileukemic effects of the tested combinations may constitute the basis for the development of novel approaches for differentiation therapy of AML. PMID:27399677

  6. Allosteric Modulation of the Calcium-sensing Receptor Rectifies Signaling Abnormalities Associated with G-protein α-11 Mutations Causing Hypercalcemic and Hypocalcemic Disorders*

    PubMed Central

    Babinsky, Valerie N.; Hannan, Fadil M.; Gorvin, Caroline M.; Howles, Sarah A.; Nesbit, M. Andrew; Rust, Nigel; Hanyaloglu, Aylin C.; Hu, Jianxin; Spiegel, Allen M.; Thakker, Rajesh V.

    2016-01-01

    Germline loss- and gain-of-function mutations of G-protein α-11 (Gα11), which couples the calcium-sensing receptor (CaSR) to intracellular calcium (Ca2+i) signaling, lead to familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2), respectively, whereas somatic Gα11 mutations mediate uveal melanoma development by constitutively up-regulating MAPK signaling. Cinacalcet and NPS-2143 are allosteric CaSR activators and inactivators, respectively, that ameliorate signaling disturbances associated with CaSR mutations, but their potential to modulate abnormalities of the downstream Gα11 protein is unknown. This study investigated whether cinacalcet and NPS-2143 may rectify Ca2+i alterations associated with FHH2- and ADH2-causing Gα11 mutations, and evaluated the influence of germline gain-of-function Gα11 mutations on MAPK signaling by measuring ERK phosphorylation, and assessed the effect of NPS-2143 on a uveal melanoma Gα11 mutant. WT and mutant Gα11 proteins causing FHH2, ADH2 or uveal melanoma were transfected in CaSR-expressing HEK293 cells, and Ca2+i and ERK phosphorylation responses measured by flow-cytometry and Alphascreen immunoassay following exposure to extracellular Ca2+ (Ca2+o) and allosteric modulators. Cinacalcet and NPS-2143 rectified the Ca2+i responses of FHH2- and ADH2-associated Gα11 loss- and gain-of-function mutations, respectively. ADH2-causing Gα11 mutations were demonstrated not to be constitutively activating and induced ERK phosphorylation following Ca2+o stimulation only. The increased ERK phosphorylation associated with ADH2 and uveal melanoma mutants was rectified by NPS-2143. These findings demonstrate that CaSR-targeted compounds can rectify signaling disturbances caused by germline and somatic Gα11 mutations, which respectively lead to calcium disorders and tumorigenesis; and that ADH2-causing Gα11 mutations induce non-constitutive alterations in MAPK signaling. PMID:26994139

  7. Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia

    PubMed Central

    De Schutter, Tineke M; Behets, Geert J; Geryl, Hilde; Peter, Mirjam E; Steppan, Sonja; Gundlach, Kristina; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Neven, Ellen

    2013-01-01

    Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification. PMID:23486515

  8. A phase I and pharmacokinetics study of intravenous calcitriol in combination with oral dexamethasone and gefitinib in patients with advanced solid tumors

    PubMed Central

    Muindi, Josephia R.; Johnson, Candace S.; Trump, Donald L.; Christy, Renee; Engler, Kristie L.

    2009-01-01

    Purpose The primary objective of this study was to determine the maximum tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in combination with a fixed oral dose of dexamethasone and gefitinib in patients with refractory solid tumors. Methods A fixed oral dose of dexamethasone of 4 mg/day was given every 12 h × 3 doses starting 12 h prior to i.v. calcitriol administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and weekly thereafter. The starting calcitriol dose level was 57 μg and escalation occurred in cohorts of three patients until the MTD was defined. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Serum calcitriol PK studies were performed on day 1 (calcitriol + dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). Results A total of 20 patients were treated. Dose-limiting hypercalcemia was observed in two out of the four patients receiving 163 mcg/week of calcitriol. Mean (±SE) peak serum calcitriol concentration (Cmax) at the MTD (125 μg/week calcitriol) was 11.17 ± 2.62 ng/ml and the systemic exposure (AUC0–72 h) of 53.30 ± 10.49 ng h/ml. The relationship between calcitriol dose and either Cmax or AUC was linear over the 57–163 μg dose range. Conclusions The addition of a low dose of dexamethasone allowed the safe escalation of calcitriol to the MTD of 125 μg/week. This dose level resulted in serum calcitriol concentrations that are associated with pre-clinical antitumor activity. However, no antitumor activity was noted clinically in patients with solid tumors. PMID:19396601

  9. CYP24A1 Inhibition Enhances the Antitumor Activity of Calcitriol

    PubMed Central

    Muindi, Josephia R.; Yu, Wei-Dong; Ma, Yingyu; Engler, Kristie L.; Kong, Rui-Xian; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    High systemic exposures to calcitriol are necessary for optimal antitumor effects. Human prostate cancer PC3 cells are insensitive to calcitriol treatment. Therefore, we investigated whether the inhibition of 24-hydroxylase (CYP24A1), the major calcitriol inactivating enzyme, by ketoconazole (KTZ) or RC2204 modulates calcitriol serum pharmacokinetics and biologic effects. Dexamethasone (Dex) was added to minimize calcitriol-induced hypercalcemia and as a steroid replacement for the KTZ inhibition of steroid biosynthesis cytochrome P450 enzymes. KTZ effectively inhibited time-dependent calcitriol-inducible CYP24A1 protein expression and enzyme activity in PC3 cells and C3H/HeJ mouse kidney tissues. Systemic calcitriol exposure area under the curve was higher in mice treated with a combination of calcitriol and KTZ than with calcitriol alone. KTZ and Dex synergistically potentiated calcitriol-mediated antiproliferative effects in PC3 cells in vitro; this effect was associated with enhanced apoptosis. After treatment with calcitriol and KTZ/Dex, although caspase-9 and caspase-3 were not activated and cytochrome c was not released by mitochondria, caspase-8 was activated and the truncated Bid protein level was increased. Translocation of apoptosis-inducing factor to the nucleus was observed, indicating a role of the apoptosis-inducing factor-mediated and caspase-independent apoptotic pathways. Calcitriol and KTZ/Dex combination suppressed the clonogenic survival and enhanced the growth inhibition observed with calcitriol alone in PC3 human prostate cancer xenograft mouse model. Our results show that the administration of calcitriol in combination with CYP24A1 inhibitor enhances antiproliferative effects, increases systemic calcitriol exposure, and promotes the activation of caspase-independent apoptosis pathway. PMID:20591973

  10. Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

    PubMed

    Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2004-05-01

    1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent. PMID:15225831

  11. Rescue of the temperature-sensitive, autosomal-recessive mutation R298S in the sodium-bicarbonate cotransporter NBCe1-A characterized by a weakened dimer and abnormal aggregation

    PubMed Central

    Gill, Harindarpal S.; Choi, Kun-Young; Kammili, Lakshmi; Popratiloff, Anastas

    2015-01-01

    Background Band keratopathy, an ocular disease that is characterized by hypercalcemia and opaque bands across the cornea, has been associated with kidney disease. Type-II renal tubular acidosis (RTA), a condition in which the kidneys fail to recover bicarbonate (HCO3−) in the proximal tubule of the nephron, results in HCO3− wastage in the urine and low blood pH. The development of these diseases is associated with autosomal-recessive mutations in the Na+-coupled HCO3− cotransporter NBCe1-A located at the basolateral membranes of either cell type. Methods We provide insight into the devastating R298S mutation found in type-II RTA-afflicted individuals using confocal-microscopy imaging of fluorescently-tagged NBCe1-A and NBCe1-A-R298S molecules expressed in human corneal endothelial and proximal tubule cells and from in-depth biophysical studies of their cytoplasmic N-terminal domains (Nt and Nt-R298S), including Nt crystal structure, melting-temperature, and homodimer dissociation constant (KD) analyses. Results We illuminate and rescue trafficking defects of the R298S mutation of NBCe1-A. The KD for Nt monomer-dimer equilibrium is established. The KD for Nt-R298S is significantly higher, but immeasurable due to environmental factors (pH, temperature, concentration) that result in dimer instability leading to precipitation. The crystal structure of Nt-dimer shows that R298 is part of a putative substrate conduit and resides near the dimer interface held together by hydrogen-bond networks. Conclusions The R298S is a temperature-sensitive mutation in Nt that results in instability of the colloidal system leading to abnormal aggregation. General significance Our findings provide new perspectives to the aberrant mechanism of certain ocular pathologies and type-II RTA associated with the R298S mutation. PMID:25743102

  12. Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

    2010-02-01

    Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

  13. Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis.

    PubMed

    Capolongo, Giovanna; Xu, Li Hao Richie; Accardo, Mariasofia; Sanduzzi, Alessandro; Stanziola, Anna Agnese; Colao, Annamaria; Agostini, Carlo; Zacchia, Miriam; Capasso, Giovambattista; Adams-Huet, Beverley; Moe, Orson W; Maalouf, Naim M; Sakhaee, Khashayar; Hsia, Connie C W

    2016-06-01

    Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia, and vitamin-D repletion is often avoided. However, the anti-inflammatory properties of vitamin-D may also be beneficial. We prospectively examined serum vitamin-D levels, calcium balance, and the effects of vitamin-D repletion in 86 AA and Caucasian patients with biopsy-proven active sarcoidosis from the USA (US) and Italy (IT) in university-affiliated outpatient clinics. Clinical features, pulmonary function, and calciotropic hormones were measured. 16 patients with vitamin-D deficiency and normal serum ionized calcium (Ca(2+)) were treated with oral ergocalciferol (50,000 IU/week) for 12 weeks. Baseline mineral parameters were similar in US (93% AA) and IT (95% Caucasian) patients irrespective of glucocorticoid treatment. Pulmonary dysfunction was less pronounced in IT patients. Nephrolithiasis (in 11% US, 17% IT patients) was associated with higher urinary calcium excretion. Vitamin-D deficiency was not more prevalent in patients compared to the respective general populations. As serum 25-hydroxyvitamin-D (25-OHD) rose postrepletion, serum 1,25-(OH)2D, γ-globulins, and the previously elevated angiotensin converting enzyme (ACE) levels declined. Asymptomatic reversible increases in Ca(2+) or urinary calcium/creatinine (Ca/Cr) developed in three patients during repletion. In conclusion, Caucasian and AA patients show similar calcium and vitamin D profiles. The higher prevalence of hypercalciuria and nephrolithiasis in sarcoidosis is unrelated to endogenous vitamin-D levels. Vitamin-D repletion in sarcoidosis is generally safe, although calcium balance should be monitored. A hypothesis that 25-OHD repletion suppresses granulomatous immune activity is provided. PMID:27053725

  14. Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

    USGS Publications Warehouse

    Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

    2014-01-01

    Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

  15. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes.

    PubMed

    Cheng, Chloe Y S; Slominski, Andrzej T; Tuckey, Robert C

    2014-10-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  16. Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes

    PubMed Central

    Cheng, Chloe Y.S.; Slominski, Andrzej T.; Tuckey, Robert C.

    2014-01-01

    20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263 nm seen for 20(OH)D3, to 290 nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID:25138634

  17. Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis

    PubMed Central

    Kourelis, Taxiarchis V.; Kumar, Shaji K.; Gertz, Morie A.; Lacy, Martha Q.; Buadi, Francis K.; Hayman, Suzanne R.; Zeldenrust, Steven; Leung, Nelson; Kyle, Robert A.; Russell, Stephen; Dingli, David; Lust, John A.; Lin, Yi; Kapoor, Prashant; Rajkumar, S. Vincent; McCurdy, Arleigh; Dispenzieri, Angela

    2013-01-01

    Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM. PMID:24145344

  18. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)₂D₃.

    PubMed

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)₂D₃ concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)₂D₃ and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  19. Phosphate-binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients.

    PubMed

    How, Priscilla P; Anattiwong, Prathana; Mason, Darius L; Arruda, Jose A; Lau, Alan H

    2011-01-01

    Lanthanum carbonate, a chewable noncalcium-containing phosphorus (P) binder, is useful for treating secondary hyperparathyroidism in patients who have hypercalcemia and cannot swallow whole tablets. However, some patients cannot chew tablets or prefer to crush and mix them with food. This study was conducted to determine the P-binding efficacy of crushed lanthanum and compare it with chewed lanthanum in hemodialysis (HD) patients. After a 1-week washout period, 11 hemodialysis patients (7 men, 4 women) were randomized to receive, in a crossover fashion, lanthanum 1000 mg 3 times daily chewed with meals and lanthanum 1000 mg 3 times daily crushed into a fine powder, mixed with applesauce and taken with meals, for 4 weeks each. Serum P was measured at the end of each washout (baseline) and weekly during treatment. Changes in serum P from baseline for crushed lanthanum were compared with chewed lanthanum using paired sample t test. Administration of crushed lanthanum resulted in a significant reduction in serum P from baseline (P reduction [mg/dL] for crushed lanthanum in week 1: 2.1 ± 0.4, week 2: 1.7 ± 0.5, week 3: 1.7 ± 0.5, week 4: 1.7 ± 0.4, P<0.05). No statistically significant differences were observed in serum P reduction from baseline and serum P attained during treatment with crushed when compared with chewed lanthanum. Crushed lanthanum is effective in reducing serum P and have similar P-binding efficacy to chewed lanthanum. Crushing lanthanum and mixing it with food can thus be an option for patients who are unable to chew or swallow whole tablets. PMID:21138519

  20. [Lanthanum carbonate in clinical practice].

    PubMed

    Torregrosa Prats, V

    2008-01-01

    Lanthanum is an element belonging to the group called rare earths. Due to its low solubility, lanthanum carbonate has been widely studied as an intestinal phosphate binder. The results of different clinical trials show that it is an effective and well-tolerated phosphate binder used in monotherapy. Serum phosphate levels are controlled in approximately 70% of patients at 5 years without causing hypercalcemia. The only significant adverse effects observed are a low percentage of gastrointestinal disturbances (6%). Lanthanum carbonate does not alter serum values of liposoluble vitamins or affect the pharmacokinetics of digoxin, warfarin, furosemide, phenytoin, ACE inhibitors or beta-blockers. However, it does alter the pharmacokinetics of ciprofloxacin (quinolones in general), tetracyclines and doxycycline. Lanthanum carbonate (Fosrenol) is available in Spain as 500 mg, 750 mg, and 1,000 mg chewable tablets, which should not be swallowed without chewing to avoid loss of efficacy. The initial dose recommended by the WHO is 2,250 mg/day, which is equivalent to one 750 mg at each meal. Lanthanum carbonate or lanthanum phosphate can be clearly visualized on a plain x-ray of the abdomen in patients who have recently ingested it. In summary, lanthanum carbonate is a widely studied potent phosphate binder, which offers the possibility of improving control of serum phosphate in patients with chronic kidney disease, without significant side effects. The fact that it is available as chewable tablets and that the number of daily tablets required has been significantly reduced will probably facilitate better patient compliance. PMID:18847414

  1. A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation

    PubMed Central

    Wolf, Myles; Weir, Matthew R.; Kopyt, Nelson; Mannon, Roslyn B.; Von Visger, Jon; Deng, Hongjie; Yue, Susan; Vincenti, Flavio

    2016-01-01

    Background Kidney transplantation corrects or improves many complications of chronic kidney disease, but its impact on disordered mineral metabolism is incompletely understood. Methods We performed a multicenter, prospective, observational cohort study of 246 kidney transplant recipients in the United States to investigate the evolution of mineral metabolism from pretransplant through the first year after transplantation. Participants were enrolled into 2 strata defined by their pretransplant levels of parathyroid hormone (PTH), low PTH (>65 to ≤300 pg/mL; n = 112), and high PTH (>300 pg/mL; n = 134) and underwent repeated, longitudinal testing for mineral metabolites. Results The prevalence of posttransplant, persistent hyperparathyroidism (PTH >65 pg/mL) was 89.5%, 86.8%, 83.1%, and 86.2%, at months 3, 6, 9, and 12, respectively, among participants who remained untreated with cinacalcet, vitamin D sterols, or parathyroidectomy. The results did not differ across the low and high PTH strata, and rates of persistent hyperparathyroidism remained higher than 40% when defined using a higher PTH threshold greater than 130 pg/mL. Rates of hypercalcemia peaked at 48% at week 8 in the high PTH stratum and then steadily decreased through month 12. Rates of hypophosphatemia (<2.5 mg/dL) peaked at week 2 and then progressively decreased through month 12. Levels of intact fibroblast growth factor 23 decreased rapidly during the first 3 months after transplantation in both PTH strata and remained less than 40 pg/mL thereafter. Conclusions Persistent hyperparathyroidism is common after kidney transplantation. Further studies should determine if persistent hyperparathyroidism or its treatment influences long-term posttransplantation clinical outcomes. PMID:26177089

  2. Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

    PubMed Central

    Cernaro, Valeria; Santoro, Domenico; Lacquaniti, Antonio; Costantino, Giuseppe; Visconti, Luca; Buemi, Antoine; Buemi, Michele

    2016-01-01

    Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium-free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro®, PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In

  3. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  4. The Contribution of CLIP2 Haploinsufficiency to the Clinical Manifestations of the Williams-Beuren Syndrome

    PubMed Central

    Vandeweyer, Geert; Van der Aa, Nathalie; Reyniers, Edwin; Kooy, R. Frank

    2012-01-01

    Williams-Beuren syndrome is a rare contiguous gene syndrome, characterized by intellectual disability, facial dysmorphisms, connective-tissue abnormalities, cardiac defects, structural brain abnormalities, and transient infantile hypercalcemia. Genes lying telomeric to RFC2, including CLIP2, GTF2I and GTF2IRD1, are currently thought to be the most likely major contributors to the typical Williams syndrome cognitive profile, characterized by a better-than-expected auditory rote-memory ability, a relative sparing of language capabilities, and a severe visual-spatial constructive impairment. Atypical deletions in the region have helped to establish genotype-phenotype correlations. So far, however, hardly any deletions affecting only a single gene in the disease region have been described. We present here two healthy siblings with a pure, hemizygous deletion of CLIP2. A putative role in the cognitive and behavioral abnormalities seen in Williams-Beuren patients has been suggested for this gene on the basis of observations in a knock-out mouse model. The presented siblings did not show any of the clinical features associated with the syndrome. Cognitive testing showed an average IQ for both and no indication of the Williams syndrome cognitive profile. This shows that CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome, nor does it lead to the Williams syndrome cognitive profile. Although contribution of CLIP2 to the phenotype cannot be excluded when it is deleted in combination with other genes, our results support the hypothesis that GTF2IRD1 and GTF2I are the main genes causing the cognitive defects associated with Williams-Beuren syndrome. PMID:22608712

  5. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure

    PubMed Central

    van Loon, Ellen P.; van de Sluis, Bart; Vervloet, Mark G.; Hoenderop, Joost G.; Bindels, René J.

    2015-01-01

    Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD), yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL) expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5), calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b), whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a) and type 3 (PIT2) were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development. PMID:26566277

  6. Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women

    PubMed Central

    2012-01-01

    Background Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age. Methods A single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters. Results Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events. Conclusions The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common. Trial registration ClinicalTrials.gov (NCT00938600) PMID:23268736

  7. Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients

    SciTech Connect

    Osborne, L.R.; Rommens, J.; Tsui, Lap-Chee |

    1996-09-01

    Williams syndrome (WS) is a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Hemizygosity of the elastin (ELN) gene can account for the vascular and connective tissue abnormalities observed in WS patients, but the genes that contribute to features such as infantile hypercalcemia, dysmorphic facies, and mental retardation remain to be identified. In addition, the size of the genomic interval commonly deleted in WS patients has not been established. In this study we report the characterization of a 500-kb region that was determined to be deleted in our collection of WS patients. A detailed physical map consisting of cosmid, P1 artificial chromosomes, and yeast artificial chromosomes was constructed and used for gene isolation experiments. Using the techniques of direct cDNA selection and genomic DNA sequencing, a three known genes (ELN, LIMK1, and RFC2), a novel gene (WSCR1) with homology to RNA-binding proteins, a gene with homology to restin, and four other putative transcription units were identified. LIMK1 is a protein kinase with two repeats of the LIM/double zinc finger motif, and it is highly expressed in brain. RFC2 is the 40-kDa ATP-binding sub-unit of replication factor C, which is known to play a role in the elongation of DNA catalyzed by DNA polymerase {delta} and {epsilon}. LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients. 56 refs., 4 figs., 3 tabs.

  8. Aluminum effects on blood chemistry and long bone development in the chick embryo.

    PubMed

    Firling, C E; Severson, A R; Hill, T A

    1994-01-01

    Body growth, blood chemistry, and long bone development of 10- to 16-day chick embryos (Gallus gallus) treated with aluminum (Al) citrate, sodium (Na) citrate, or sodium chloride (NaCl) were investigated. Two administration protocols were used. Acutely-treated embryos received 6.0 mumol Al citrate or Na citrate on day 8 of incubation. Chronically-treated embryos received a daily dose of 1.5 mumol Al citrate or Na citrate beginning on day 8 of incubation. For both protocols, Al citrate and Na citrate had no significant influence on viability or body weight. Al citrate-treated embryos had: (a) significantly shorter mean tibia lengths by day 16 of incubation, (b) a consistently lower ratio of tibia length: body weight on all days investigated, and (c) a persistent mid-diaphyseal malformation (angulation) of the femur and tibia. Spatially correlated with the malformation was a calcification defect detected by alizarin red S staining of intact tibias and the accumulation of aluminum as demonstrated by acid solochrome azurine staining of histological sections. Aluminum was localized at the mineralization front of the osteogenic collar surrounding the cartilage core of the tibia. Aluminum citrate or Na citrate had no significant effect on serum total calcium, inorganic phosphorus, total alkaline phosphatase activity, or creatinine, except for a transitory hypercalcemia (day 10) and phosphatemia (days 10 and 12) in Al citrate-treated embryos. The concomitant localization of Al and the early calcification defect in the region of tibial malformation implicate aluminum in the pathogenesis of the skeletal abnormality. PMID:7998819

  9. Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis

    PubMed Central

    Lu, J; Lu, J; Chen, W; Huo, Y; Huang, X; Hou, J

    2014-01-01

    The aim of this study was to understand the clinical features and treatment outcome of Chinese patients with multiple myeloma (MM). This retrospective study enrolled 940 newly diagnosed inpatients (median age, 59 years; immunoglobulin (Ig)D isotype, 6.5%) with complete follow-up data at three centers. In all, 85.8% of patients were of Durie-Salmon stage III and 48.3% were of International Staging System (ISS) stage III at diagnosis. Also, 9.6% of patients had extramedullary plasmacytoma. Compared with IgG, IgD-type patients were diagnosed at a younger age, and more patients were of ISS stage III, with hypercalcemia, elevated levels of lactate dehydrogenase, hyperuricemia, renal dysfunction and 1q21 amplification (P=0.03). The overall survival (OS) benefit was more prominent in IgG than in IgD when patients received bortezomib; however, they showed no significant difference when they received older therapies such as melphalan combined with prednisone or vincristine combined with adriamycin and dexamethasone. Fluorescence in situ hybridization (FISH) results showed that 17.6% had 17p13 deletion. Conventional cytogenetics revealed that 13.3% were hypodiploid and those cases had the worst survival, but hyperdiploid cases (9.3%) did not show any survival benefit compared with those with a normal karyotype (77.4%). Median OS and progression-free survival for all patients were 54 and 26 months, respectively. Significant factors for survival by multivariate analysis were gender, ISS stage, number of FISH abnormalities and extramedullary disease. MM in mainland China presents with different features, with patients being of younger age and having higher risk and more survival benefit in IgG patients receiving bortezomib. PMID:25127393

  10. Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

    PubMed Central

    Toledo, Sergio PA; Lourenço, Delmar M; Santos, Marcelo Augusto; Tavares, Marcos R; Toledo, Rodrigo A; de Menezes Correia-Deur, Joya Emilie

    2009-01-01

    Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and

  11. Raman spectroscopy of bone metastasis

    NASA Astrophysics Data System (ADS)

    Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

    2012-02-01

    Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

  12. Clinical potential for vitamin D as a neoadjuvant for photodynamic therapy of nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Rollakanti, Kishore

    2015-03-01

    Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of human cancer worldwide. Effective therapies include surgical excision, cryotherapy, and ionizing radiation, but all of these cause scarring. ALA-based PDT is a non-scarring modality used routinely for NMSC in Europe but not in the USA, primarily due to lingering uncertainties about efficacy. We have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can be used as neoadjuvants, i.e., can be given as a pretreatment prior to ALA-PDT, to improve the efficacy of tumor killing in mouse models of NMSC. Vitamin D (VD3) is the most recent neoadjuvant on this list. In this presentation we make the case that VD3 may be superior to the other agents to improve results of ALA-PDT skin cancer treatment. The active form of VD3 (calcitriol) is available topically as a pharmaceutical grade cream or ointment (FDA-approved for psoriasis), and works well for boosting ALA-PDT tumor treatment in mouse models. For deep tumors not reachable by a topical route, calcitriol can be given systemically and is very effective, but carries a risk of causing hypercalcemia as a side effect. To circumvent this risk, we have conducted experiments with the natural dietary form of VD3 (cholecalciferol), and showed that this improves ALA-PDT efficacy almost to the same extent as calcitriol. Because cholecalciferol does not increase serum calcium levels, this represents a potentially extremely safe approach. Data in mouse models of BCC and SCC will be presented.

  13. Effect of Transdermal Teriparatide Administration on Bone Mineral Density in Postmenopausal Women

    PubMed Central

    Cosman, Felicia; Lane, Nancy E.; Bolognese, Michael A.; Zanchetta, Jose R.; Garcia-Hernandez, Pedro A.; Sees, Karen; Matriano, James A.; Gaumer, Kim; Daddona, Peter E.

    2010-01-01

    Context: Treatment of osteoporosis with an anabolic agent, teriparatide [human PTH 1-34 (TPTD)], is effective in reducing incident fractures, but patient resistance to daily sc injections has limited its use. A novel transdermal patch, providing a rapid, pulse delivery of TPTD, may provide a desirable alternative. Objective: The aim of the study was to determine the safety and efficacy of a novel transdermal TPTD patch compared to placebo patch and sc TPTD 20-μg injection in postmenopausal women with osteoporosis. Design: Our study consisted of 6-month, randomized, placebo-controlled, positive control, multidose daily administration. Patients: We enrolled 165 postmenopausal women (mean age, 64 yr) with osteoporosis. Interventions: A TPTD patch with a 20-, 30-, or 40-μg dose or a placebo patch was self-administered daily for 30-min wear time, or 20 μg of TPTD was injected daily. Outcomes: The primary efficacy measure was mean percentage change in lumbar spine bone mineral density (BMD) from baseline at 6 months. Results: TPTD delivered by transdermal patch significantly increased lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P < 0.001). TPTD 40-μg patch increased total hip BMD compared to both placebo patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type I N-terminal propeptide and C-terminal cross-linked telopeptide of type I collagen) increased from baseline in a dose-dependent manner in all treatment groups and were all significantly different from placebo patch (P < 0.001). All treatments were well tolerated, and no prolonged hypercalcemia was observed. Conclusion: Transdermal patch delivery of TPTD in postmenopausal women with osteoporosis for 6 months is safe and effective in increasing lumbar spine and total hip BMD. PMID:19858319

  14. Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients

    PubMed Central

    Jeong, Sohyun; Kim, In-Wha; Oh, Kook-Hwan; Han, Nayoung; Joo, Kwon Wook; Kim, Hyo Jin; Oh, Jung Mi

    2016-01-01

    Background Secondary hyperparathyroidism (SHPT) is one of the major risk factors of morbidity and mortality in end-stage renal disease. Cinacalcet effectively controls SHPT without causing hypercalcemia and hyperphosphatemia. However, there is significant inter-individual response variance to cinacalcet treatment. Therefore, we aimed to evaluate the genetic effects related with parathyroid hormone regulation as factors for cinacalcet response variance. Methods Patients with a diagnosis of SHPT based on intact parathyroid hormone (iPTH) >300 pg/mL on dialysis were included in this study. They were over 18 years and have been treated by cinacalcet for more than 3 months. Responders and nonresponders were grouped by the serum iPTH changes. Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis. Results After adjusting for age, sex, and calcium level, CASR rs1042636 (odds ratio [OR]: 0.066, P=0.027) and rs1802757 (OR: 10.532, P=0.042) were associated with cinacalcet response. The association of haplotypes of CASR rs1042636, rs10190, and rs1802757; GCC (OR: 0.355, P=0.015); and ATT (OR: 2.769, P=0.014) with cinacalcet response was also significant. Conclusion We obtained supporting information of the associations between cinacalcet response and CASR polymorphisms. CASR single nucleotide polymorphisms (SNPs) rs1802757, rs1042636, and haplotypes of rs1042636, rs10190, and rs1802757 were significantly associated with cinacalcet response variance. PMID:27468225

  15. How do We Manage Coronary Artery Disease in Patients with CKD and ESRD?

    PubMed

    Choi, Hoon Young; Park, Hyeong Cheon; Ha, Sung Kyu

    2014-12-01

    Chronic kidney disease (CKD) has been shown to be an independent risk factor for cardiovascular events. In addition, patients with pre-dialysis CKD appear to be more likely to die of heart disease than of kidney disease. CKD accelerates coronary artery atherosclerosis by several mechanisms, notably hypertension and dyslipidemia, both of which are known risk factors for coronary artery disease. In addition, CKD alters calcium and phosphorus homeostasis, resulting in hypercalcemia and vascular calcification, including the coronary arteries. Mortality of patients on long-term dialysis therapy is high, with age-adjusted mortality rates of about 25% annually. Because the majority of deaths are caused by cardiovascular disease, routine cardiac catheterization of new dialysis patients was proposed as a means of improving the identification and treatment of high-risk patients. However, clinicians may be uncomfortable exposing asymptomatic patients to such invasive procedures like cardiac catheterization, thus noninvasive cardiac risk stratification was investigated widely as a more palatable alternative to routine diagnostic catheterization. The effective management of coronary artery disease is of paramount importance in uremic patients. The applicability of diagnostic, preventive, and treatment modalities developed in nonuremic populations to patients with kidney failure cannot necessarily be extrapolated from clinical studies in non-kidney failure populations. Noninvasive diagnostic testing in uremic patients is less accurate than in nonuremic populations. Initial data suggest that dobutamine echocardiography may be the preferred diagnostic method. PCI with stenting is a less favorable alternative to CABG, however, it has a faster recovery time, reduced invasiveness, and no overall mortality difference in nondiabetic and non-CKD patients compared with CABG. CABG is associated with reduced repeat revascularizations, greater relief of angina, and increased long term

  16. Statin Use is Associated with Improved Survival in Patients Undergoing Surgery for Renal Cell Carcinoma

    PubMed Central

    Kaffenberger, Samuel D.; Lin-Tsai, Opal; Stratton, Kelly L.; Morgan, Todd M.; Barocas, Daniel A.; Chang, Sam S.; Cookson, Michael S.; Herrell, S. Duke; Smith, Joseph A.; Clark, Peter E.

    2014-01-01

    Purpose To determine whether statin use at time of surgery is associated with survival following nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). Statins are thought to exhibit a protective effect on cancer incidence and possibly cancer survival in a number of malignancies; to date, no studies have shown an independent association between statin use and mortality in RCC. Methods A retrospective cohort study of 916 patients who underwent radical or partial nephrectomy for RCC from 2000–2010 at a single institution was performed. Primary outcomes were overall (OS) and disease-specific survival (DSS). Univariable survival analyses were performed using the Kaplan-Meier and log-rank methods. Multivariable analysis was performed using a Cox proportional hazards model. The predictive discrimination of the models was assessed with Harrell’s c-index. Results Median follow-up of the entire cohort was 42.5 months. The three-year OS estimate was 83.1% (95%CI, 77.6–87.3%) for statin users and 77.3% (95%CI, 73.7–80.6%) for non-statin users (p=0.53). Three-year DSS was 90.9% (95%CI, 86.3–94.0%) for statin users and 83.5% (95%CI, 80.1–86.3%) for non-statin users (p=0.015). After controlling for age, ASA class, pT stage, pN stage, metastatic status, pre-operative anemia and corrected hypercalcemia, and blood type, statin use at time of surgery was independently associated with improved OS (HR 0.62, 95%CI 0.43–0.90; p=0.011) and DSS (HR 0.48, 95%CI 0.28–0.83; p=0.009). The multivariable model for DSS had excellent predictive discrimination with a c-index of 0.91. Conclusions These data suggest that statin usage at time of surgery is independently associated with improved OS and DSS in patients undergoing surgery for RCC. PMID:25456998

  17. PHEX Mimetic (SPR4-Peptide) Corrects and Improves HYP and Wild Type Mice Energy-Metabolism

    PubMed Central

    Zelenchuk, Lesya V.; Hedge, Anne-Marie; Rowe, Peter S. N.

    2014-01-01

    Context PHEX or DMP1 mutations cause hypophosphatemic-rickets and altered energy metabolism. PHEX binds to DMP1-ASARM-motif to form a complex with α5β3 integrin that suppresses FGF23 expression. ASARM-peptides increase FGF23 by disrupting the PHEX-DMP1-Integrin complex. We used a 4.2 kDa peptide (SPR4) that binds to ASARM-peptide/motif to study the DMP1-PHEX interaction and to assess SPR4 for the treatment of energy metabolism defects in HYP and potentially other bone-mineral disorders. Design Subcutaneously transplanted osmotic pumps were used to infuse SPR4-peptide or vehicle (VE) into wild-type mice (WT) and HYP-mice (PHEX mutation) for 4 weeks. Results SPR4 partially corrected HYP mice hypophosphatemia and increased serum 1.25(OH)2D3. Serum FGF23 remained high and PTH was unaffected. WT-SPR4 mice developed hypophosphatemia and hypercalcemia with increased PTH, FGF23 and 1.25(OH)2D3. SPR4 increased GAPDH HYP-bone expression 60× and corrected HYP-mice hyperglycemia and hypoinsulinemia. HYP-VE serum uric-acid (UA) levels were reduced and SPR4 infusion suppressed UA levels in WT-mice but not HYP-mice. SPR4 altered leptin, adiponectin, and sympathetic-tone and increased the fat mass/weight ratio for HYP and WT mice. Expression of perlipin-2 a gene involved in obesity was reduced in HYP-VE and WT-SPR4 mice but increased in HYP-SPR4 mice. Also, increased expression of two genes that inhibit insulin-signaling, ENPP1 and ESP, occurred with HYP-VE mice. In contrast, SPR4 reduced expression of both ENPP1 and ESP in WT mice and suppressed ENPP1 in HYP mice. Increased expression of FAM20C and sclerostin occurred with HYP-VE mice. SPR4 suppressed expression of FAM20C and sclerostin in HYP and WT mice. Conclusions ASARM peptides and motifs are physiological substrates for PHEX and modulate osteocyte PHEX-DMP1-α5β3-integrin interactions and thereby FGF23 expression. These interactions also provide a nexus that regulates bone and energy metabolism. SPR4 suppression of

  18. 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression.

    PubMed

    Liu, Eva S; Martins, Janaina S; Raimann, Adalbert; Chae, Byongsoo Timothy; Brooks, Daniel J; Jorgetti, Vanda; Bouxsein, Mary L; Demay, Marie B

    2016-05-01

    X-linked hypophosphatemia (XLH) is characterized by impaired renal tubular reabsorption of phosphate owing to increased circulating FGF23 levels, resulting in rickets in growing children and impaired bone mineralization. Increased FGF23 decreases renal brush border membrane sodium-dependent phosphate transporter IIa (Npt2a) causing renal phosphate wasting, impairs 1-α hydroxylation of 25-hydroxyvitamin D, and induces the vitamin D 24-hydroxylase, leading to inappropriately low circulating levels of 1,25-dihydroxyvitamin D (1,25D). The goal of therapy is prevention of rickets and improvement of growth in children by phosphate and 1,25D supplementation. However, this therapy is often complicated by hypercalcemia and nephrocalcinosis and does not always prevent hyperparathyroidism. To determine if 1,25D or blocking FGF23 action can improve the skeletal phenotype without phosphate supplementation, mice with XLH (Hyp) were treated with daily 1,25D repletion, FGF23 antibodies (FGF23Ab), or biweekly high-dose 1,25D from d2 to d75 without supplemental phosphate. All treatments maintained normocalcemia, increased serum phosphate, and normalized parathyroid hormone levels. They also prevented the loss of Npt2a, α-Klotho, and pERK1/2 immunoreactivity observed in the kidneys of untreated Hyp mice. Daily treatment with 1,25D decreased urine phosphate losses despite a marked increase in bone FGF23 mRNA and in circulating FGF23 levels. Daily 1,25D was more effective than other treatments in normalizing the growth plate and metaphyseal organization. In addition to being the only therapy that normalized lumbar vertebral height and body weight, daily 1,25D therapy normalized bone geometry and was more effective than FGF23Ab in improving trabecular bone structure. Daily 1,25D and FGF23Ab improved cortical microarchitecture and whole-bone biomechanical properties more so than biweekly 1,25D. Thus, monotherapy with 1,25D improves growth, skeletal microarchitecture, and bone strength

  19. [Effect of low doses of oral pamidronate (APD) on the calcemia of osteopenic or osteoporotic patients].

    PubMed

    Roldan, E J; Kerzberg, E M; Castelli, G; Lloret, A P

    1996-01-01

    Oral pamidronate (APD) at high doses (400-900 mg/day) is employed as antiresorptive agent for the treatment of Paget's disease. In some occasions hypocalcemia may occur, and is interpreted as a relative overdosage. To avoid this complication and the consequent PTH release, supplementation with calcium salts is recommended. In osteoporotic syndromes, APD is prescribed at a lower dosage (200 mg/day) and currently calcium or vitamin D are also systematically added. But at this low dose the antiresorptive activity is partial and transient. In order to observe the effects on calcemia of multiple therapy, data from 129 postmenopausal women with the diagnosis of osteopenia or osteoporosis treated with 200 mg/day of APD soft capsules during 6-10 months, were gathered retrospectively. The first group (n: 13) received APD alone; the second group was supplemented with 1 g/day calcium salts (n: 61); the third group received 0.015-0.025 mg/day vitamina D (n: 10); and the fourth received both calcium plus vitamin D (n: 45). In samples of 24 h, urine, calcium, creatinine, hydroxyproline, and serum total calcium were measured before and after therapy. No hypocalcemia was detected. All groups, except the one treated with APD alone, showed a significant trend to increase their calcemia values between normal ranges (Table 1, 2). Only in one patient treated with APD + Ca + vitamin D, hypercalcemia was detected. Measuring HOP/Cr and Ca/Cr in urine as resorption markers, showed that 27% of the APD + Ca group and 33% of the APD + Ca + vitamin D group showed scant or any repercussion on mentioned resorption indexes, meaning that the response to APD could be hindered in those cases. In conclusion, while using low doses of oral APD, calcium salts should not be systematically recommended. There is no trend to hypocalcemia. Furthermore, calcium salts may favor drug interactions and so induce digestive side effects or poor responses. Calcium supplementation should be prescribed only on the

  20. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia

    PubMed Central

    Carpenter, Thomas O.; Imel, Erik A.; Ruppe, Mary D.; Weber, Thomas J.; Klausner, Mark A.; Wooddell, Margaret M.; Kawakami, Tetsuyoshi; Ito, Takahiro; Zhang, Xiaoping; Humphrey, Jeffrey; Insogna, Karl L.; Peacock, Munro

    2014-01-01

    Background. X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate reabsorption, and low serum concentrations of phosphate (inorganic phosphorus, Pi) and 1,25-dihydroxyvitamin D [1,25(OH)2D]. KRN23 is a human anti-FGF23 antibody developed as a potential treatment for XLH. Here, we have assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of KRN23 following a single i.v. or s.c. dose of KRN23 in adults with XLH. Methods. Thirty-eight XLH patients were randomized to receive a single dose of KRN23 (0.003–0.3 mg/kg i.v. or 0.1–1 mg/kg s.c.) or placebo. PK, PD, immunogenicity, safety, and tolerability were assessed for up to 50 days. Results. KRN23 significantly increased the maximum renal tubular threshold for phosphate reabsorption (TmP/GFR), serum Pi, and 1,25(OH)2D compared with that of placebo (P < 0.01). The maximum serum Pi concentration occurred later following s.c. dosing (8–15 days) compared with that seen with i.v. dosing (0.5–4 days). The effect duration was dose related and persisted longer in patients who received s.c. administration. Changes from baseline in TmP/GFR, serum Pi, and serum 1,25(OH)2D correlated with serum KRN23 concentrations. The mean t1/2 of KRN23 was 8–12 days after i.v. administration and 13–19 days after s.c. administration. Patients did not exhibit increased nephrocalcinosis or develop hypercalciuria, hypercalcemia, anti-KRN23 antibodies, or elevated serum parathyroid hormone (PTH) or creatinine. Conclusion. KRN23 increased TmP/GFR, serum Pi, and serum 1,25(OH)2D. The positive effect of KR23 on serum Pi and its favorable safety profile suggest utility for KRN23 in XLH patients. Trial registration. Clinicaltrials.gov NCT00830674. Funding. Kyowa Hakko Kirin Pharma, Inc. PMID:24569459

  1. Influence of the use of phosphate binders on serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis: A retrospective and prospective study

    PubMed Central

    Setiani Agus, Lusi; Effendi, Imam; Abdillah, Syamsudin

    2013-01-01

    Hypercalcemia–hyperphosphatemia is an unavoidable consequence of end-stage chronic kidney disease and common in hemodialytic patients. Calcium carbonate (CaCO3) is one type of phosphate binder used widely and prescribed in patients undergoing hemodialysis, aiming to control the levels of calcium and phosphate. These drugs are most effective if taken with meals. This study aimed to evaluate the use of phosphate binders in hemodialysis patients and the factors that influence the success of phosphate binder therapy by experimental studies with retrospective data collection through the medical records and prospectively through the questionnaire and interviews with patients. The research was conducted in the Unit Hemodialysis building floor 8 of Cipto Mangunkusumo Hospital, Jakarta. The data were collected in a retrospective way for two months (January–February 2013) and a prospective study in March–April 2013. Patients included were stage 5 chronic kidney disease patients who underwent hemodialysis in hemodialysis ward of Cipto Mangunkusumo Hospital. Patients who had data of serum levels at the beginning of the use of calcium phosphate and the final data in 2013 got the phosphate binder therapy. Results Ninety six patients with stage 5 chronic kidney disease who underwent hemodialysis had been using phosphate binder for 3 years in average. Patient evaluation showed that hypocalcemia was obtained in 23%; normokalemia in 42.7% and hypercalcemia in 34.3%. While the percentage of patients with hipofosfatemia14, 6%, normofosfatemia 32.3% and 53.1% hyperphosphatemia. Results obtained by the prospective analysis of factors that affect the success of the use of phosphate binder therapy are related to how the routine use of phosphate binders is made by the patient. Chi square test showed a significance of 0.000 (p < 0.05), the effect of 54%. Conclusion We can conclude there are many events happening such as hyperphosphatemia in hemodialysis patients that use phosphate

  2. Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis.

    PubMed

    Bro, S; Rasmussen, R A; Handberg, J; Olgaard, K; Feldt-Rasmussen, B

    1998-02-01

    carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients. PMID:9469496

  3. Considerations about the effectiveness and cost effectiveness of therapies in the treatment of hyperphosphataemia.

    PubMed

    Plagemann, Thomas; Prenzler, Anne; Mittendorf, Thomas

    2011-01-01

    Because of an elevated serum phosphate level, patients who suffer from chronic kidney failure frequently tend to have cardiovascular calcification and are therefore exposed to a higher probability of a fatal event. Phosphate binders are able to reduce these negative effects. Currently, there are primarily two groups of phosphate binders (calcium-containing and calcium-free phosphate binders) which are considered to be almost equally effective in terms of binding of free phosphate. There are, however, a few disadvantages of the two groups. While the calcium-containing binders are associated with an increased risk of hypercalcemia, which is dose dependent, calcium-free binders have been criticized as being too expensive. As the expenditure for patients suffering from chronic kidney failure increases from year to year, as a result of increasing prevalence, there is a growing need for an alternative to existing phosphate binders. The study presented here therefore summarizes available information for the novel combination preparation OsvaRen® (calcium acetate/magnesium carbonate) as an alternative therapy to the calcium-free phosphate binder Renagel® (sevelamer-hydrochloride) and to calcium-containing preparations.The results of this systematic review showed that OsvaRen® is at least equally effective in the regulation of serum phosphate level as Renagel®. In particular, OsvaRen® shows no clinically relevant difference in terms of the control of the serum calcium levels compared to Renagel® and thereby does not increase the risk of a hypercalcaemia, in contrast to pure calcium-based phosphate binders. On the other hand, Renagel® therapy is much more frequently associated with gastrointestinal side-effects, a tendency to result in higher tablet burden for patients and high medication costs. The CALMAG study showed that OsvaRen® was at least as effective and safe in terms of controlling serum phosphate and serum calcium levels as Renagel® while, at the same time

  4. 25-Hydroxyvitamin D Can Interfere With a Common Assay for 1,25-Dihydroxyvitamin D in Vitamin D Intoxication

    PubMed Central

    Hawkes, Colin P.; Schnellbacher, Sarah; Singh, Ravinder J.

    2015-01-01

    Context: Vitamin D intoxication is characterized by elevated serum 25-hydroxyvitamin D (25(OH)D) and suppressed serum 1,25-dihydroxvitamin D (1,25(OH)2D). We evaluated two adolescents with hypercalcemia due to vitamin D intoxication; both had elevated serum 1,25(OH)2D by Diasorin RIA, but normal serum 1,25(OH)2D concentrations by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Objective: This study aimed to determine the effect of 25(OH)D2 and 25(OH)D3 on 1,25(OH)2D concentration determined using RIA and LC-MS/MS. Methods: Pools of normal serum and an artificial serum matrix were prepared and aliquots were spiked with >99% pure 25(OH)D2 or 25(OH)D3 (50–700 ng/mL). Samples were maintained at 4°C or heated to 56°C, and the concentrations of vitamin D metabolites were measured by LC-MS/MS and Diasorin RIA. Results: Median 1,25(OH)2D increased by 114% with RIA and 21% with LC-MS/MS with addition of 100 ng/mL 25(OH)D3, and 349% (RIA) and 117% (LC-MS/MS) with 700 ng/mL of 25(OH)D3. Each 1-ng/mL increase in 25(OH)D3 increased 1,25(OH)2D by 0.231 pg/mL (RIA) and 0.121 pg/mL (LC-MS/MS). Spiking with 25(OH)D2 led to similar changes. Heat inactivation of serum, and using an artificial serum matrix, were associated with similar effects of 25(OH)D on 1,25(OH)2D assays. Conclusions: Vitamin D intoxication with high serum levels of 25(OH)D2 or 25(OH)D3 can be associated with elevated levels of 1,25(OH)2D due to interference in a commonly used RIA. A similar but attenuated effect also occurs when 1,25(OH)2D is measured using LC-MS/MS but does not seem to be clinically significant. The basis for this effect on the LC-MS/MS assay is presently uncertain. PMID:26120794

  5. Efficacy and safety of lanthanum carbonate on chronic kidney disease–mineral and bone disorder in dialysis patients: a systematic review

    PubMed Central

    2013-01-01

    Background Chronic kidney disease–mineral and bone disorder (CKD–MBD) is a common complication in CKD patients, particularly in those with end-stage renal disease that requires dialysis. Lanthanum carbonate (LC) is a potent, non-aluminum, non-calcium phosphate binder. This systematic review evaluates the efficacy and safety of LC in CKD-MBD treatment for maintenance-dialysis patients. Methods A systematic review and meta-analysis on randomized controlled trials (RCTs) and quasi-RCTs was performed to assess the efficacy and safety of LC in maintenance hemodialysis or peritoneal dialysis patients. Analysis was performed using the statistical software Review Manager 5.1. Results Sixteen RCTs involving 3789 patients were identified and retained for this review. No statistical difference was found in all-cause mortality. The limited number of trials was insufficient to show the superiority of LC over other treatments in lowering vascular calcification or cardiovascular events and in improving bone morphology, bone metabolism, or bone turn-over parameters. LC decreased the serum phosphorus level and calcium × phosphate product (Ca × P) as compared to placebo. LC, calcium carbonate (CC), and sevelamer hydrochloride (SH) were comparable in terms of controlling the serum phosphorus, Ca × P product, and intact parathyroid hormone (iPTH) levels. However, LC resulted in a lower serum calcium level and a higher bone-specific alkaline phosphatase level compared with CC. LC had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with SH. LC-treated patients appeared to have a higher rate of vomiting and lower risk of hypercalcemia, diarrhea, intradialytic hypotension, cramps or myalgia, and abdominal pain. Meta-analysis showed no significant difference in the incidence of other side effects. Accumulation of LC in blood and bone was below toxic levels. Conclusions LC has high efficacy in lowering serum phosphorus and iPTH levels without

  6. Resorbing bone stimulates tumor cell growth. A role for the host microenvironment in bone metastasis.

    PubMed

    Manishen, W J; Sivananthan, K; Orr, F W

    1986-04-01

    Demineralized extracts of bone matrix and conditioned media from cultured fetal rat calvaria have been reported to contain growth stimulatory activity for bone cells. To investigate the potential role of these local bone growth factors in the development of bone metastases, we chose the Walker 256 carcinosarcoma, a rat mammary tumor which causes osteolytic bone metastases and hypercalcemia. 45Ca-labeled, 19-day fetal Sprague-Dawley rat calvaria were cultured for 96 hours in BGJb medium. Walker cells from ascites tumors or cultures were grown in unconditioned media or in conditioned media harvested from the bone cultures, in the presence of 10% fetal calf serum. Media were changed every 2 days, cells were counted daily for 5 days, and 3H-thymidine uptake into acid insoluble residues was measured. The growth of tumor cells was 5-6-fold greater in conditioned media than in unconditioned media and the effect was dose dependent. Cells cultured in conditioned media demonstrated a approximately 3-fold enhancement of 3H-thymidine incorporation. Generation of growth stimulatory activity correlated with the extent of bone resorption, measured by release of 45Ca from the fetal parietal bones (r = 0.85; P less than 0.001). Conditioned media from bones cultured with 10(-7) M prostaglandin E2 (PGE2) contained greater amounts of growth stimulatory activity than untreated conditioned media, but PGE2 itself did not stimulate tumor cell growth. Addition of 3.5 mM PO4 to bone cultures blocked bone resorption and the generation of growth factors. Growth stimulatory activity was stable to heat (56 C for 30 minutes) and trypsin digestion, with an apparent molecular weight of less than 17,000 daltons by high-performance liquid chromatography. Conditioned medium also stimulated the growth of 13762 rat mammary adenocarcinoma cells, MB-MDA-231 human breast carcinoma cells, TE-85 osteosarcoma cells, a murine fibrosarcoma and rat embryonic fibroblasts, with the most potent effects noted for

  7. The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial

    PubMed Central

    Van Buren, Peter N.; Lewis, Julia B.; Dwyer, Jamie P.; Greene, Tom; Middleton, John; Sika, Mohammed; Umanath, Kausik; Abraham, Josephine D.; Arfeen, Shahabul S.; Bowline, Isai G.; Chernin, Gil; Fadem, Stephen Z.; Goral, Simin; Koury, Mark; Sinsakul, Marvin V.; Weiner, Daniel E.

    2016-01-01

    Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (−2.04 ± 1.99 [SD] vs −2.18 ± 2.25 mg/dL, respectively; P = 0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22 ± 0.90 vs 0.31 ± 0.95 mg/dL; P = 0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (−167.1 ± 399.8 vs −152.7 ± 392.1 pg/mL; P = 0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open

  8. An open-label phase 2 trial of dabrafenib plus trametinib in patients with previously treated BRAF V600E–mutant metastatic non-small cell lung cancer

    PubMed Central

    Planchard, David; Besse, Benjamin; Groen, Harry J M; Souquet, Pierre-Jean; Quoix, Elisabeth; Baik, Christina S; Barlesi, Fabrice; Kim, Tae Min; Mazieres, Julien; Novello, Silvia; Rigas, James R; Upalawanna, Allison; D’Amelio, Anthony M; Zhang, Pingkuan; Mookerjee, Bijoyesh; Johnson, Bruce E

    2016-01-01

    Background BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated antitumor activity in patients with BRAF V600E (Val600Glu)–mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF V600E–mutant NSCLC may improve efficacy over BRAF-inhibitor monotherapy based on observations in BRAF V600–mutant melanoma. Methods In this phase 2, multicenter, nonrandomized, open-label study of patients with pretreated metastatic BRAF V600E–mutant NSCLC, antitumor activity and safety of oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) were evaluated. Adult patients (≥ 18 years) with documented progression following at least one prior platinum-based chemotherapy and no more than three prior systemic anticancer therapies were enrolled. Patients with prior BRAF or MEK inhibitor treatment were ineligible. Patients with brain metastases were permitted to enroll only if the lesions were asymptomatic, untreated (or stable > 3 weeks after local therapy if treated), and measured < 1 cm. The primary endpoint was investigator-assessed overall response, which was assessed by intention-to-treat in the protocol-defined population (≥ second-line); safety was also assessed in this population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Fifty-seven patients previously treated with systemic chemotherapy for metastatic BRAF V600E–mutant NSCLC were enrolled. The investigator-assessed overall response was 63·2% (36 of 57; 95% CI 49·3–75·6). Serious adverse events were reported in 32 (56%) of 57 patients and included pyrexia (16%; 9 of 57), anemia (5%; 3 of 57), confusional state (4%; 2 of 57), decreased appetite (4%; 2 of 57), hemoptysis (4%; 2 of 57), hypercalcemia (4%; 2 of 57), nausea (4%; 2 of 57), and cutaneous squamous cell

  9. Cooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemia.

    PubMed

    Sharabani, Hagar; Izumchenko, Eugene; Wang, Qing; Kreinin, Rita; Steiner, Michael; Barvish, Zeev; Kafka, Michael; Sharoni, Yoav; Levy, Joseph; Uskokovic, Milan; Studzinski, George P; Danilenko, Michael

    2006-06-15

    1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D(3) in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D(-) murine myelomonocytic leukemia cells induced by 1 nM 1,25D(3) or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 microM) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0 + G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 microg Ro25-4020 in Balb/c mice bearing WEHI-3B D(-) tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 microg Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia. PMID:16395705

  10. Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics

    PubMed Central

    2013-01-01

    Background The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. Method The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. Results BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by >75% after infection with oncolytic viruses. Conclusions These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53

  11. 1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression

    PubMed Central

    Dai, Zhang-han; Tan, Bei; Yang, Hong; Wang, Ou; Qian, Jia-ming; Lv, Hong

    2015-01-01

    Aim To investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats. Methods Experimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Results Rats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P < 0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P = 0.049, P = 0.040, respectively), histological colonic damage score (P = 0.010, P = 0.005, respectively), and MPO activity (P = 0.0003, P = 0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P = 0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P < 0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P < 0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r = 0.654, P < 0.001). Conclusion TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression. PMID:26718757

  12. Androgen Receptor Regulation of Vitamin D Receptor in Response of Castration-Resistant Prostate Cancer Cells to 1α-Hydroxyvitamin D5

    PubMed Central

    Mooso, Benjamin; Madhav, Anisha; Johnson, Sherra; Roy, Mohana; Moore, Mary E.; Moy, Christabel; Loredo, Grace A.; Mehta, Rajendra G.; Vaughan, Andrew T.M.; Ghosh, Paramita M.

    2010-01-01

    Calcitriol (1,25(OH)2D3) is cytostatic for prostate cancer (CaP) but had limited therapeutic utility due to hypercalcemia-related toxicities, leading to the development of low-calcemic calcitriol analogs. We show that one analog, 1α-hydroxyvitamin D5 (1α(OH)D5), induced apoptosis in castration-sensitive LNCaP prostate cancer cells but, unlike calcitriol, did not increase androgen receptor (AR) transcriptional activity. LNCaP-AI, a castrate-resistant (CRCaP) LNCaP subline, was resistant to 1α(OH)D5 in the presence of androgens; however, androgen withdrawal (AWD), although ineffective by itself, sensitized LNCaP-AI cells to 1α(OH)D5. Investigation of the mechanism revealed that the vitamin D receptor (VDR), which mediates the effects of 1α(OH)D5, is downregulated in LNCaP-AI cells compared to LNCaP in the presence of androgens, whereas AWD restored VDR expression. Since LNCaP-AI cells expressed higher AR compared to LNCaP and AWD decreased AR, this indicated an inverse relationship between VDR and AR. Further, AR stimulation (by increased androgen) suppressed VDR, while AR downregulation (by ARsiRNA) stimulated VDR levels and sensitized LNCaP-AI cells to 1α(OH)D5 similar to AWD. Another cell line, pRNS-1-1, although isolated from a normal prostate, had lost AR expression in culture and adapted to androgen-independent growth. These cells expressed the VDR and were sensitive to 1α(OH)D5, but restoration of AR expression suppressed VDR levels and induced resistance to 1α(OH)D5 treatment. Taken together, these results demonstrate negative regulation of VDR by AR in CRCaP cells. This effect is likely mediated by prohibitin (PHB), which was inhibited by AR transcriptional activity and stimulated VDR in CRCaP but not castrate-sensitive cells. Therefore, in castration-sensitive cells, although the AR negatively regulates PHB, this does not affect VDR expression, whereas in CRCaP cells, negative regulation of PHB by the AR results in concomitant negative regulation of

  13. Prevalence and severity of disordered mineral metabolism in patients with chronic kidney disease: A study from a tertiary care hospital in India

    PubMed Central

    Vikrant, Sanjay; Parashar, Anupam

    2016-01-01

    Background: Disordered mineral metabolism is common complications of chronic kidney disease (CKD). However, there are limited data on the pattern of these disturbances in Indian CKD population. Materials and Methods: This was a prospective observational study of CKD-mineral and bone disorder (CKD-MBD) over a period of 3 years. The biochemical markers of CKD-MBD, namely, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), and 25-hydoxyvitamin Vitamin D3 (25OHD), were measured in newly diagnosed CKD Stage 3–5 and prevalent CKD Stage 5D adult patients. Results: A total of 462 patients of CKD Stage 3–5D were studied. The frequency of various biochemical abnormalities was hypocalcemia (23.8%), hypercalcemia (5.4%), hypophosphatemia (2.8%), hyperphosphatemia (55.4%), raised alkaline phosphatase (56.9%), secondary hyperparathyroidism (82.7%), and hypoparathyroidism (1.5%). 25OHD was done in 335 (72.5%) patients and 90.4% were found to have Vitamin D deficiency. About 70.6% of the patients had iPTH levels were above kidney disease outcomes quality initiative (KDOQI) target range. Nondiabetic CKD as compared to diabetic CKD had a higher alkaline phosphatase (P = 0.016), a higher iPTH (P = 0.001) a higher proportion of patients with iPTH above KDOQI target range (P = 0.09), and an elevated alkaline phosphatase (P = 0.004). The 25OHD levels were suggestive of severe Vitamin D deficiency in 33.7%, Vitamin D deficiency in 45.4%, and Vitamin D insufficiency in 11.3% patients. There was a significant positive correlation between iPTH with alkaline phosphatase (r = 0.572, P = 0.001), creatinine (r = 0.424, P = 0.001), and phosphorus (r = 0.241, P = 0.001) and a significant negative correlation with hemoglobin (r = −0.325, 0.001), age (r = −0.169, P = 0.002), and 25OHD (r = −0.126, P = 0.021). On multivariate logistic regression analysis, an elevated alkaline phosphatase was a significant predictor of hyperparathyroidism (odds ratio 9.7, 95

  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. Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial1234

    PubMed Central

    Ng, Kimmie; Scott, Jamil B; Drake, Bettina F; Chan, Andrew T; Hollis, Bruce W; Chandler, Paulette D; Bennett, Gary G; Giovannucci, Edward L; Gonzalez-Suarez, Elizabeth; Meyerhardt, Jeffrey A; Emmons, Karen M; Fuchs, Charles S

    2014-01-01

    Background: Association studies have suggested that lower circulating 25-hydroxyvitamin D [25(OH)D] in African Americans may partially underlie higher rates of cardiovascular disease and cancer in this population. Nonetheless, the relation between vitamin D supplementation and 25(OH)D concentrations in African Americans remains undefined. Objective: Our primary objective was to determine the dose-response relation between vitamin D and plasma 25(OH)D. Design: A total of 328 African Americans in Boston, MA, were enrolled over 3 winters from 2007 to 2010 and randomly assigned to receive a placebo or 1000, 2000, or 4000 IU vitamin D3/d for 3 mo. Subjects completed sociodemographic and dietary questionnaires, and plasma samples were drawn at baseline and 3 and 6 mo. Results: Median plasma 25(OH)D concentrations at baseline were 15.1, 16.2, 13.9, and 15.7 ng/mL for subjects randomly assigned to receive the placebo or 1000, 2000, or 4000 IU/d, respectively (P = 0.63). The median plasma 25(OH)D concentration at 3 mo differed significantly between supplementation arms at 13.7, 29.7, 34.8, and 45.9 ng/mL, respectively (P < 0.001). An estimated 1640 IU vitamin D3/d was needed to raise the plasma 25(OH)D concentration to ≥20 ng/mL in ≥97.5% of participants, whereas a dose of 4000 IU/d was needed to achieve concentrations ≥33 ng/mL in ≥80% of subjects. No significant hypercalcemia was seen in a subset of participants. Conclusions: Within African Americans, an estimated 1640 IU vitamin D3/d was required to achieve concentrations of plasma 25(OH)D recommended by the Institute of Medicine, whereas 4000 IU/d was needed to reach concentrations predicted to reduce cancer and cardiovascular disease risk in prospective observational studies. These results may be helpful for informing future trials of disease prevention. This trial was registered at clinicaltrials.gov as NCT00585637. PMID:24368437

  16. The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers

    PubMed Central

    Ekwaru, John Paul; Zwicker, Jennifer D.; Holick, Michael F.; Giovannucci, Edward; Veugelers, Paul J.

    2014-01-01

    Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets. PMID:25372709

  17. [Preclinical toxicology of bisphosphonates].

    PubMed

    Mondelo, N; Peluffo, V A; Parma, M D; Cointry, G R; Capozza, R F; Ferretti, J L; Piccinni, E; Montuori, E

    1997-01-01

    Bisphosphonates regulate bone turnover by inhibiting osteoclastic bone resorption. Due to their pharmacodynamic and pharmacokinetic characteristics, bisphosphonates have a special pharmacotoxicological profile related to their high degree of specificity: low or non-existent distribution in soft tissues and strong affinity for calcified tissues. Some general conclusions may be drawn from the pre-clinical toxicological studies, whose main aim is to identify the toxicity target organ/s and estimate the safety margins of a "prospective therapeutic agent" in laboratory animals. They are based on our own results and on data from the available literature as regards various bisphosphonates: Alendronate, Clodronate, Etidronate, Olpadronate and Pamidronate. Generally, very high doses of bisphosphonates are required to produce in different levels and incidence various extra-skeletical toxic side effects: local reaction, hypocalcemia (and its consequences on the cardiovascular system and the possibility of tetany), affection of the dental structures and renal dysfunction. Most of side effects may be related to the low solubility in biological fluids, the formation of calcium complexes, the potent inhibitory effect of endogenous or induced bone resorption as well as to its main excretion pathway. Some other side effects (on the eye, lungs and liver), may be related to repeated excessive high doses. A safety margin of 200 to 300 : 1 between the "toxic" and "pharmacological" doses may be estimated if the total quantity of Olpadronate given to various animal species in toxicological studies and in pharmacodynamic experimental models (osteopenias due to estrogen deprivation or immobilization and retinoid-induced hypercalcemia) is considered. If the toxic doses in animals are related to the highest doses suggested for human beings, then the ratio increases from 300 to 1000 : 1 depending on the pathology and the route of administration. As regards their effect on the bone

  18. Calcium Input Potentiates the Transforming Growth Factor (TGF)-β1-dependent Signaling to Promote the Export of Inorganic Pyrophosphate by Articular Chondrocyte*

    PubMed Central

    Cailotto, Frederic; Reboul, Pascal; Sebillaud, Sylvie; Netter, Patrick; Jouzeau, Jean-Yves; Bianchi, Arnaud

    2011-01-01

    Transforming growth factor (TGF)-β1 stimulates extracellular PPi (ePPi) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was up-regulated by TGF-β1 activation of ERK1/2 and Ca2+-dependent protein kinase C (PKCα). Thus, we investigated mechanisms by which calcium could affect ePPi metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-β1 under extracellular (eCa2+) or cytosolic Ca2+ (cCa2+) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePPi levels (radiometric assay), and cCa2+ input (fluorescent probe). Voltage-operated Ca2+-channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-β1 elevated cCa2+ and ePPi levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa2+ dose-dependent manner. TGF-β1 effects were suppressed by cCa2+ chelation or L- and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKCα, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca2+. SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-β1. TGF-β1 promotes input of eCa2+ through opening of L- and T-VOCs, to potentiate ERK1/2 and PKCα signaling cascades, resulting in an enhanced activation of Ank promoter and ePPi production in chondrocyte. PMID:21471198

  19. A Novel Humanized GLP-1 Receptor Model Enables Both Affinity Purification and Cre-LoxP Deletion of the Receptor

    PubMed Central

    Jun, Lucy S.; Showalter, Aaron D.; Ali, Nosher; Dai, Feihan; Ma, Wenzhen; Coskun, Tamer; Ficorilli, James V.; Wheeler, Michael B.; Michael, M. Dodson; Sloop, Kyle W.

    2014-01-01

    Class B G protein-coupled receptors (GPCRs) are important regulators of endocrine physiology, and peptide-based therapeutics targeting some of these receptors have proven effective at treating disorders such as hypercalcemia, osteoporosis, and type 2 diabetes mellitus (T2DM). As next generation efforts attempt to develop novel non-peptide, orally available molecules for these GPCRs, new animal models expressing human receptor orthologs may be required because small molecule ligands make fewer receptor contacts, and thus, the impact of amino acid differences across species may be substantially greater. The objective of this report was to generate and characterize a new mouse model of the human glucagon-like peptide-1 receptor (hGLP-1R), a class B GPCR for which established peptide therapeutics exist for the treatment of T2DM. hGLP-1R knock-in mice express the receptor from the murine Glp-1r locus. Glucose tolerance tests and gastric emptying studies show hGLP-1R mice and their wild-type littermates display similar physiological responses for glucose metabolism, insulin secretion, and gastric transit, and treatment with the GLP-1R agonist, exendin-4, elicits similar responses in both groups. Further, ex vivo assays show insulin secretion from humanized islets is glucose-dependent and enhanced by GLP-1R agonists. To enable additional utility, the targeting construct of the knock-in line was engineered to contain both flanking LoxP sites and a C-terminal FLAG epitope. Anti-FLAG affinity purification shows strong expression of hGLP-1R in islets, lung, and stomach. We crossed the hGLP-1R line with Rosa26Cre mice and generated global Glp-1r−/− animals. Immunohistochemistry of pancreas from humanized and knock-out mice identified a human GLP-1R-specific antibody that detects the GLP-1R in human pancreas as well as in the pancreas of hGLP-1r knock-in mice. This new hGLP-1R model will allow tissue-specific deletion of the GLP-1R, purification of potential GLP-1R partner

  20. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.

    PubMed

    Abramovitch, Shirley; Sharvit, Efrat; Weisman, Yosef; Bentov, Amir; Brazowski, Eli; Cohen, Gili; Volovelsky, Oded; Reif, Shimon

    2015-01-15

    1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis. PMID:25214398