BACKGROUND & AIMS: :Hypercalcemia occurring in a patient with an islet cell carcinoma of the pancreas suggests the diagnosis of Multiple Endocrine Neoplasia Type I and associated hyperparathyroidism. We describe a patient with an islet cell carcinoma and hypercalcemia in whom low concentrations of PTH, the absence of skeletal metastases, hypophosphatemia, and elevated nephrogenous cAMP alternatively suggested the syndrome of humoral hypercalcemia of malignancy. The peptide PTHrP was measured in the patient's serum during the course of therapy by an immunoradiometric assay directed toward the midportion of the molecule. Hypercalcemia was treated with an investigational aminobisphosphonate. The concentration of PTHrP[56-86] increased over time and fell after the patient received chemotherapy directed toward the islet cell tumor.

背景与目标： 胰岛细胞癌患者中发生的高钙血症提示诊断为I型多发性内分泌肿瘤和相关的甲状旁腺功能亢进。我们描述了患有胰岛细胞癌和高钙血症的患者，其中低浓度的PTH，不存在骨骼转移，低血磷症和肾源性cAMP升高提示恶性体液高钙血症综合征。在治疗过程中，通过针对分子中部的免疫放射分析法测定了患者血清中的PTHrP肽。高血钙症是通过研究用氨基双膦酸盐治疗的。患者接受针对胰岛细胞瘤的化疗后，PTHrP [56-86]的浓度随时间增加而下降。

BACKGROUND & AIMS: :Humoral hypercalcemia of malignancy is a common metabolic disturbance associated with solid tumors, but it also occurs in lymphoma patients. Among these, low grade B-cell lymphoma accounts for only few cases, in which secretion of parathyroid hormone-related protein (PTHrP) remains even exceptional. We report the very rare case of a patient with a CLL type low grade leukemic B-cell lymphoma showing PTHrP-related hypercalcemia without evidence of bone lesions. Using immunohistochemistry, we demonstrate the cytoplasmic expression of PTHrP by the lymphoma cells in the bone marrow obtained at the onset of hypercalcemia. We postulate a pathogenetic role of leukemic cell production and secretion of PTHrP in hypercalcemia in low grade leukemic B-cell lymphoma.

背景与目标： ：恶性肿瘤的体液高钙血症是与实体瘤相关的常见代谢紊乱，但它也发生在淋巴瘤患者中。其中，低度B细胞淋巴瘤仅占少数病例，其中甲状旁腺激素相关蛋白（PTHrP）的分泌甚至异常。我们报道了CLL型低级白血病B细胞淋巴瘤患者的罕见病例，显示PTHrP相关的高钙血症而没有骨病变的证据。使用免疫组织化学，我们证明高钙血症发作时获得的骨髓中的淋巴瘤细胞的PTHrP的细胞质表达。我们推测白血病细胞的产生和PTHrP分泌在低度白血病B细胞淋巴瘤高钙血症中的致病作用。

BACKGROUND & AIMS: :A number of factors have been proposed as potential mediators of the syndrome of humoral hypercalcemia of malignancy (HHM), but to date no firm cause-and-effect relationship has been established. We attempted to establish such a relationship by determining whether the presence or absence of adenylate cyclase-stimulating activity (ACSA) in the media of cultured tumor cells predicted the occurrence of the syndrome of HHM when these cell lines were grown in nude mice in vivo. Conditioned media from 35 human renal carcinoma cell lines were surveyed for ACSA in the PTH-sensitive rat osteosarcoma 17/2.8 cell assay. 12 lines were positive (mean, 13.7-fold stimulation, range, 3.0 to 44.0), and 23 lines were negative (mean, 1.2-fold stimulation, range, 0.9 to 1.5). We were successful in establishing five of the positive and six of the negative lines in three to five nude mice per line. Mice implanted with the positive lines uniformly became hypercalcemic (mean serum calcium, 15.8 mg/dl), whereas mice implanted with the negative lines uniformly remained normocalcemic (mean serum calcium, 9.5 mg/dl), in spite of comparable mean tumor size. Acid-urea tumor extracts from each of four hypercalcemic animals contained potent in vitro ACSA (mean, 15.9-fold stimulation), while 5/5 extracts from normocalcemic animals did not (mean, 1.4-fold stimulation). Our study demonstrates that in this model system in vitro ACSA is a reliable predictive marker for HHM in vivo. Whether the protein responsible for this activity is also the mediator of the bone resorption seen in HHM remains to be demonstrated.

背景与目标： ：已提出许多因素作为恶性体液性高钙血症综合征（HHM）的潜在介体，但迄今为止，尚未建立牢固的因果关系。我们试图通过确定培养的肿瘤细胞培养基中腺苷酸环化酶刺激活性（ACSA）的存在与否来预测当这些细胞系在裸鼠体内生长时HHM综合征的发生，从而建立这种关系。在PTH敏感的大鼠骨肉瘤17 / 2.8细胞分析中，对来自35种人肾癌细胞系的条件培养基的ACSA进行了调查。 12线阳性（平均13.7倍刺激，范围3.0至44.0），23线阴性（平均1.2倍刺激，范围0.9至1.5）。我们成功地在每行三到五只裸鼠中建立了五个阳性线和六个阴性线。植入阳性线的小鼠均匀地变成高钙血症（平均血清钙，15.8 mg / dl），而植入阴性线的小鼠均匀地保持正常血钙性（平均血清钙，9.5 mg / dl），尽管平均肿瘤大小相当。来自四只高钙血症动物中每只的酸性尿素肿瘤提取物均含有有效的体外ACSA（平均刺激15.9倍），而来自正常高钙血症动物的5/5提取物则没有（平均1.4倍刺激）。我们的研究表明，在体外该模型系统中，ACSA是体内HHM的可靠预测标记。在HHM中所见，负责这种活性的蛋白质是否也是骨吸收的介体，尚待证实。

BACKGROUND & AIMS: :Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.

背景与目标： ：在正常受试者的基线状态期间以及在通过盐水和钙输注改变其血清钙浓度的过程中，确定了适合血清钙浓度的尿环AMP（UcAMP）。将其与UcAMP在76例高钙血症患者和5例低钙血症患者中进行了比较。在56例原发性甲状旁腺功能亢进患者中，有54例UcAMP的血钙浓度过高，其中2例有肾功能衰竭。在四名患有维生素D中毒，结节病，乳碱综合征和噻嗪类引起的高钙血症的患者中，以及在五名由于甲状旁腺功能低下引起的低钙血症的患者中，UcAMP的血清钙浓度适当较低。在16例非甲状旁腺肿瘤患者中，有10例的UcAMP水平过高，提示异位甲状旁腺激素（PTH）介导的高钙血症，而6例的UcAMP水平较低，表明其高钙血症是由于除PTH以外的溶骨因子引起的。 UcAMP，血清钙浓度和羧基末端免疫反应性PTH之间的相关性表明，随机UcAMP是循环的生物活性PTH的敏感准确反映。如果有足够的肾功能（血清肌酐浓度低于2.0 mg / dl），则随机表示为mumol / g肌酐并根据血清钙浓度进行分析的UcAMP会完全分离PTH和非PTH介导的高钙血症患者。

BACKGROUND & AIMS: :Hypercalcemia in accelerated phase of chronic myelogenous leukemia (CML) is very rare. Its pathogenesis is considered humoral hypercalcemia of malignancies mediated by parathyroid hormone-related protein (PTHrP). In severe hypercalcemia, calcifications in kidneys, skin, vessels, heart, and stomach may occur. Our two cases were admitted because of severe hypercalcemia in accelerated phase of CML. On Tc-99m methylene diphosphonate (MDP) bone scintigraphies, a marked tracer accumulation was seen in the lung, heart, stomach and kidney. We report increased tracer accumulation of multiple organs on Tc-99m MDP bone scintigraphy in two rare hypercalcemic patients with CML.

背景与目标： ：慢性粒细胞性白血病（CML）加速期的高钙血症非常罕见。其发病机理被认为是由甲状旁腺激素相关蛋白（PTHrP）介导的恶性体液性高钙血症。在严重的高钙血症中，可能会在肾脏，皮肤，血管，心脏和胃中发生钙化。我们的两个病例是由于CML加速期严重的高钙血症而入院的。在Tc-99m二磷酸二甲酯（MDP）骨显像仪上，在肺，心脏，胃和肾脏中发现了明显的示踪剂蓄积。我们报告了两名罕见的高钙血症伴CML患者在Tc-99m MDP骨闪烁显像仪上多个器官的示踪剂积累增加。

BACKGROUND & AIMS: :Hypercalcemia with concomitant elevation of serum parathyroid hormone (PTH) and PTH-related protein (PTHrP) levels was found in a patient with advanced gastric carcinoma and multiple liver metastases. The most common features are hypercalcemia associated with hypersecretion of PTHrP and physiological suppression of PTH secretion in the syndrome of humoral hypercalcemia of malignancy (HHM). Although we initially made a diagnosis of primary hyperparathyroidism concomitant with HHM due to gastric cancer, diagnostic imaging studies, such as echography, CT, sestamibi scintigraphy, and autopsy findings, did not reveal evidence of any parathyroid tumors or ectopic parathyroid glands in the mediastinum. Both primary and metastatic tumor cells showed positive staining with PTH-specific antibody as well as PTHrP-specific antibody on immunohistochemical examination. PTH concentration in the cytosolic fraction of the metastatic tumor was elevated compared to that from a control patient with no calcium metabolic disorders in vitro. These findings indicated that PTH secreted ectopically by gastric cancer cells, not by parathyroid glands, caused hypercalcemia in this patient. To our knowledge, this is the first case report of PTH-secreting gastric carcinoma cells. We report the case and a review of the previous reported PTH-secreting non-parathyroid tumors along with the mechanisms of secretion.

背景与目标： ：患有晚期胃癌和多发肝转移的患者发现高钙血症并伴有血清甲状旁腺激素（PTH）和PTH相关蛋白（PTHrP）升高。在恶性体液性高钙血症（HHM）综合征中，最常见的特征是与PTHrP过度分泌相关的高钙血症和PTH分泌的生理抑制。尽管我们最初诊断出因胃癌而伴有HHM的原发性甲状旁腺功能亢进症，但影像学检查（如回波描记术，CT，司他他比闪烁显像和尸检结果）并未显示出纵隔中有任何甲状旁腺肿瘤或异位甲状旁腺的证据。在免疫组织化学检查中，原发性和转移性肿瘤细胞均显示PTH特异性抗体和PTHrP特异性抗体呈阳性染色。与没有钙代谢异常的对照组患者相比，转移性肿瘤的胞质部分中的PTH浓度升高。这些发现表明，胃癌细胞而不是甲状旁腺分泌的异位PTH引起该患者高钙血症。据我们所知，这是分泌PTH的胃癌细胞的首例报道。我们报告该病例，并对先前报道的分泌PTH的非甲状旁腺肿瘤及其分泌机制进行了回顾。

BACKGROUND & AIMS: Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.

背景与目标： 患有肿瘤引起的高钙血症患者的癌症通常会产生一种模仿甲状旁腺激素活性的循环因子，称为甲状旁腺激素相关蛋白。食道鳞状细胞癌患者中肿瘤引起的高钙血症的发生率似乎很高，并且在一些原发性食道癌中已显示甲状旁腺激素相关蛋白的存在。在本研究中，我们调查了食管转移性鳞状细胞癌并发肿瘤引起的高钙血症的患者中甲状旁腺激素相关蛋白的存在。通过免疫组织化学搜索蛋白质，并通过逆转录酶-聚合酶链反应和S1核酸酶分析研究信使RNA。在肝转移中检测到信使RNA和蛋白，而正常食管粘膜和原发性癌症未通过S1核酸酶分析表达可检测的蛋白或信使RNA。在所有这些组织中，包括正常的食管粘膜，逆转录酶-聚合酶链反应均为阳性。总之，本案表明，食管鳞状细胞癌引起的肿瘤引起的高钙血症可能是由大部分由肝转移释放的甲状旁腺激素相关蛋白引起的。

BACKGROUND & AIMS: :Parathyroid hormone-like adenylate cyclase-stimulating proteins (hACSPs) have been implicated as one of the calcemic, bone-resorbing agents in patients with humoral hypercalcemia of malignancy. We report the synthesis of an amino-terminal hACSP fragment, Tyr36 hACSP (1-36) amide. The synthetic hACSP is a potent agonist of renal membrane adenylate cyclase (Km, 1.7 X 10(-10)) and of bone cell adenylate cyclase (Km 1 X 10(-9)M). It is a potent bone-resorbing agent in vitro, stimulating 45Ca release from fetal rat long bones at a concentration of 10(-9) M. When infused via osmotic minipumps into rats, it is also a potent calcemic factor in vivo, inducing a rise in serum calcium from (mean +/- SD) 10.6 +/- 0.6 to 19.7 +/- 3.2 mg/dl when infused at 1.4 micrograms/h and from 9.9 +/- 0.7 to 11.4 +/- 1.2 mg/dl when infused at 0.14 micrograms/h. These findings indicate that biologically active hACSP fragments can be synthesized. One such synthetic peptide possesses the in vitro and in vivo bioactivities demonstrated in native, tumor-derived hACSPs. It is also a potent calcemic, bone-resorbing agent.

背景与目标： ：甲状旁腺激素样腺苷酸环化酶刺激蛋白（hACSPs）已被认为是恶性体液性高钙血症患者的钙化，骨吸收剂之一。我们报告了氨基末端hACSP片段，Tyr36 hACSP（1-36）酰胺的合成。合成的hACSP是肾膜腺苷酸环化酶（Km，1.7 X 10（-10））和骨细胞腺苷酸环化酶（Km 1 X 10（-9）M）的有效激动剂。它是一种有效的骨吸收剂，在体外以10（-9）M的浓度刺激胎儿长骨中45Ca的释放。当通过渗透性微型泵注入大鼠体内时，它也是一种有效的钙化因子，可在体内诱导钙的释放。当以1.4微克/小时注入时，血清钙从（平均值/-标准差）从10.6 /-0.6增至19.7 /-3.2 mg / dl，当以0.14微克/小时注入时从9.9 /-0.7至11.4 /-1.2 mg / dl H。这些发现表明可以合成具有生物活性的hACSP片段。一种这样的合成肽具有在天然的，肿瘤来源的hACSP中证明的体外和体内生物活性。它也是强效的钙化，骨吸收剂。

BACKGROUND & AIMS: :Patients on hemodialysis may develop severe and symptomatic hypercalcemia if skeletal buffering is ineffective. We report a case of persistent hypercalcemia with apparent extrarenal vitamin D synthesis. Associated aluminium intoxication was suggested on desferrioxamine challenge and adynamic uremic osteodystrophy confirmed on bone biopsy. Plasma calcitriol did not suppress with corticosteroids but did with ketoconazole. No other evidence for underlying granulomatous disease was found. We discuss our approach to less usual causes of hypercalcemia, and emphasise the pitfalls associated with factitious disorders.

背景与目标： ：如果骨骼缓冲无效，则血液透析患者可能会出现严重的症状性高钙血症。我们报告一例持续的高钙血症，伴有明显的肾外维生素D合成。建议在去铁胺攻击中伴有铝中毒，并在骨活检中证实无动力尿毒症骨营养不良。血浆骨化三醇对皮质类固醇激素无抑制作用，但对酮康唑有抑制作用。没有发现其他潜在肉芽肿疾病的证据。我们讨论了减少高钙血症的常见原因的方法，并强调了与人为疾病相关的陷阱。

BACKGROUND & AIMS: BACKGROUND:Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS:CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS:The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION:Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

背景与目标： 背景：以前，膳食补充富含欧米伽3脂肪酸二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）的亮氨酸和鱼油可降低C26荷瘤小鼠恶病质相关的结局。为了进一步探讨相关的过程和机制，我们研究了血浆Ca2水平的变化，甲状旁腺激素相关蛋白（PTHrP）的参与及其与环氧合酶2（COX-2）的可能相互作用。
方法：对CD2F1小鼠皮下接种C26腺癌细胞或进行假手术，分为：（1）对照组，（2）荷瘤对照组和（3）接受实验饮食的荷瘤小鼠。 20天后，确定身体和器官的质量以及血浆总Ca2水平。此外，在培养的C26细胞中研究了DHA，EPA和亮氨酸对PTHrP产生的影响。
结果：亮氨酸和鱼油的组合减少了肿瘤相关的高钙血症。血浆Ca2水平与car体质量和多个器官质量负相关。在体外，DHA能够减少C26细胞产生的PTHrP。结果表明，该效应独立于COX-2抑制而发生。
结论：我们的结果表明，可通过富含亮氨酸和鱼油的营养干预措施来改善与癌症相关的高钙血症。鱼油的作用可能与DHA诱导的肿瘤引起的PTHrP排泄减少有关。

BACKGROUND & AIMS: :Calcimimetic agents increase the sensitivity of calcium sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone. There are still limited data on the treatment of renal transplant patients with severe hypercalcemia and hyperparathyroidism with calcimimetics (cinacalcet). We describe two such renal transplant patients with chronic kidney disease Stage 3 who presented with persistent hypercalcemia (serum calcium 11.5-12 mg/dl) and refractory hyperparathyroidism (iPTH 194-547 pg/ml). Control of hypercalcemia with cinacalcet (serum calcium <10 mg/dl) resulted also in an improvement of hyperparathyroidism, but with a slower rate than that of the lowering of serum calcium. Addition of a vitamin D analog together with the calcimimetic agent resulted in faster control of the resistant hyperparathyroidism in both patients (iPTH <145 pg/ml) with clinical improvement and without any side effect. It seems that this new agent will improve our clinical approach of renal bone disease permitting a more integrated and successful treatment of hyperparathyroidism and its consequences on patients with chronic kidney disease.

背景与目标： ：拟钙剂可提高甲状旁腺钙敏感受体的敏感性，并抑制血清钙水平和甲状旁腺激素。拟钙剂（西那卡塞）治疗严重高钙血症和甲状旁腺功能亢进的肾移植患者的数据仍然有限。我们描述了两名患有慢性肾脏疾病第3期的此类肾脏移植患者，他们持续存在高钙血症（血清钙11.5-12 mg / dl）和难治性甲状旁腺功能亢进症（iPTH 194-547 pg / ml）。西那卡塞控制高钙血症（血清钙<10 mg / dl）也可改善甲状旁腺功能亢进，但其速度要比降低血清钙慢。维生素D类似物与拟钙剂的结合可更快控制两名患者的耐药性甲状旁腺功能亢进（iPTH <145 pg / ml），且临床上有所改善，且无任何副作用。看来这种新药将改善我们的肾骨疾病临床治疗方法，从而可以更全面，更成功地治疗甲状旁腺功能亢进及其对慢性肾脏病患者的后果。

BACKGROUND & AIMS: :Hypercalcemia is often associated with a urinary concentration defect. During antidiuresis, organic osmolytes [sorbitol, myo-inositol, taurine, and glycerophosphorylcholine (GPC)] accumulate in the renal inner medulla and are essential for urinary concentration. To clarify the relationship between organic osmolytes and urinary concentration defect in hypercalcemia, examination was made of the effects of hypercalcemia on renal medullary osmolytes content. Rats were put in a state of hypercalcemia by a calcium-rich diet supplemented with CaCO3 (2.5%/wt) and daily s.c. injection of 1.25(OH)2VitD3 (1.6 micrograms/kg). They were killed on days 7 and 14. Hypercalcemia induced a urinary concentration defect. Myo-inositol, sorbitol, and GPC contents in the renal medulla were significantly reduced. Aldose reductase activity decreased significantly. Hypercalcemia would thus appear to directly affect renal medullary content of organic osmolytes, thereby modifying renal concentration ability.

背景与目标： 高钙血症通常与尿液浓度缺陷有关。在抗利尿过程中，有机渗透物[山梨糖醇，肌醇，牛磺酸和甘油磷酸胆碱（GPC）]积累在肾内髓质中，对尿液浓缩至关重要。为了阐明高渗血症中有机渗透物与尿液浓度缺陷之间的关系，研究了高钙血症对肾髓质渗透物含量的影响。高钙饮食补充CaCO3（2.5％/ wt），每日皮下注射使大鼠处于高钙血症状态。注射1.25（OH）2VitD3（1.6微克/千克）。他们在第7天和第14天被杀死。高钙血症引起尿液浓缩缺陷。肾髓质中的肌醇，山梨糖醇和GPC含量显着降低。醛糖还原酶活性明显降低。因此，高钙血症似乎会直接影响有机渗透液的肾脏髓质含量，从而改变肾脏的浓缩能力。

BACKGROUND & AIMS: :Hypercalcemia of malignancy, usually reported in adults in advanced stages, is rare in children. A 4-year-old boy presented with intermittent episodes of severe hypercalcemia, which improved with intravenous hydration therapy, furosemide and bisphosphonates as the initial manifestation of occult acute lymphoblastic leukemia. Pediatricians should rule out hematological malignancy in patients with severe hypercalcemia.

背景与目标： 恶性高钙血症通常在成人中晚期报道，在儿童中很少见。一个4岁男孩表现出间歇性严重高钙血症发作，并通过静脉水合作用，速尿和双膦酸盐治疗作为隐匿性急性淋巴细胞白血病的初始表现而得到改善。儿科医生应排除严重高钙血症患者的血液系统恶性肿瘤。

BACKGROUND & AIMS: Squamous cell lung carcinoma cells obtained from a patient who presented with leukocytosis and hypercalcemia were transplanted into nude mice and a serially transplantable cell line, OKa-N-1, was established. The nude mice transplanted with OKa-N-1 cells displayed leukocytosis and hypercalcemia. Serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) were both elevated in these mice. In vitro cultivation of this tumor cell line gave rise to a clonal cell line, OKa-C-1. Nude mice transplanted with the OKa-C-1 cell line also showed leukocytosis and hypercalcemia with high serum G-CSF and PTHrP levels. The culture supernatant of OKa-C-1 contained high levels of G-CSF and PTHrP. Immunohistochemical studies showed the expression of PTHrP in OKa-C-1 cells. Reverse transcription polymerase chain reaction revealed the presence of G-CSF and PTHrP mRNA in this cell line. Dexamethasone treatment inhibited the transcription of G-CSF and PTHrP genes. This new human squamous carcinoma cell line, OKa-C-1, would be useful for studying the mechanism of simultaneous production of G-CSF and PTHrP and their control in cancer patients with leukocytosis and hypercalcemia.

背景与目标： 从患有白细胞增多和高钙血症的患者获得的鳞状细胞肺癌细胞移植到裸鼠中，并建立了可移植的细胞系OKa-N-1。移植有OKa-N-1细胞的裸鼠表现出白细胞增多和高钙血症。这些小鼠的粒细胞集落刺激因子（G-CSF）和甲状旁腺激素相关蛋白（PTHrP）的血清水平均升高。该肿瘤细胞系的体外培养产生了克隆细胞系OKa-C-1。移植有OKa-C-1细胞系的裸鼠还表现出白细胞增多和高钙血症，血清G-CSF和PTHrP水平较高。 OKa-C-1的培养上清液含有高水平的G-CSF和PTHrP。免疫组织化学研究显示PTHrP在OKa-C-1细胞中表达。逆转录聚合酶链反应显示该细胞系中存在G-CSF和PTHrP mRNA。地塞米松治疗抑制了G-CSF和PTHrP基因的转录。这种新的人类鳞状细胞癌细胞系OKa-C-1，对于研究白细胞增多和高钙血症的癌症患者同时产生G-CSF和PTHrP的机制及其控制很有用。

BACKGROUND & AIMS: BACKGROUND/AIMS:Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. MATERIALS:This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. RESULTS:The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). CONCLUSION:The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

背景与目标： 背景/目的：血管钙化在包括肾脏移植受者（KTRs）在内的慢性肾脏疾病中是常见且进展的。但是，尚未完全阐明与KTR的主动脉钙化（AoC）进展相关的危险因素。在本研究中，我们评估了AoC并检查了其在KTR中的进展相关的因素。
材料：这是一项前瞻性纵向研究，包括98个KTR。我们使用Agatston评分定量研究了肾下腹AoC，这是通过多层计算机断层扫描测量的。在进行基线调查后，三年后进行了一次随访扫描，并再次获得了Agatston评分。在对多个混杂因素进行调整后，使用非线性回归通过多变量分析检查了影响第二Agatston得分的实验室数据的变化。
结果：第二Agagston得分显着高于基线Agatston得分（p <0.001）。调整混杂因素后，校正后的血清钙的变化与第二Agatston得分表现出显着的非线性相关性（非线性度p = 0.022 /校正后血清钙的作用p = 0.031）。此外，基线AoC与校正后血清钙对AoC进展的影响存在相互作用，基线Agatston评分较高的患者高钙血症的影响更大（p = 0.049）。
结论：本研究显示高钙血症是KTRs发生肾下腹AoC的危险因素。此外，高钙血症对血管钙化程度更高的患者的影响更大。