Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide.

OBJECTIVE: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). MATERIAL AND METHOD: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. RESULTS: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). CONCLUSION: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

Analysis of the reg1alpha and reg1beta gene transcripts in patients with fibrocalculous pancreatopathy.

Fibrocalculous pancreatopathy is a form of diabetes, associated with tropical chronic calcific pancreatitis, in which islet beta-cell loss and pancreatic stone formation are found. It is likely to be a multifactorial disease with both genetic and environmental components. Regenerating (reg) gene encodes protein that has been involved in pancreatic lithogenesis and the regeneration of islet cells and therefore the abnormality of reg genes could be associated with fibrocalculous pancreatopathy. In this study, regla and reg1beta mRNAs were isolated from peripheral blood lymphocytes obtained from 16 patients with fibrocalculous pancreatopathy, 42 patients with type 1 diabetes, 37 patients with type 2 diabetes, and 22 normal controls. mRNAs were amplified by reverse-transcription polymerase chain reaction (RT-PCR) and analysed by a single strand conformation polymorphism (SSCP) technique. The reg1alpha and reg1beta mRNAs were isolated, indicating the ectopic expression of these genes in peripheral blood lymphocytes; however, variation among mobility patterns was not observed in the SSCP analysis of the RT-PCR products. The results indicated that there was no abnormality of the regla and reg1beta mRNAs obtained from the study groups.

Flow cytometry for the analysis of T cells expressing CD69 after stimulation with glutamic acid decarboxylase.

Type 1 diabetes mellitus is a T-cell mediated autoimmune disease in which the insulin-producing pancreatic beta cells are selectively destroyed. We recently found that the detection of cell-mediated immune response to glutamic acid decarboxylase (GAD) was more useful than the detection of specific autoantibodies for the diagnosis of type 1 diabetes mellitus. In this study, we established a flow cytometric analysis for the detection of activated T cells in whole venous blood, obtained from diabetic patients and normal controls after stimulation by GAD. Two millitiers of peripheral venous blood and 6 hours incubation time were used for performing the test. It was found that 33% (3/9) type 1 diabetic patients, 7.7% (1/13) type 2 diabetic patients and neither patients with fibrocalculous pancreatopathy nor normal controls had > or = 20% CD8+ T cells expressing CD69. The results suggest that flow cytometry may be a useful tool for the detection of surrogate markers of type 1 diabetes mellitus.

Association between estrogen receptor concentration in breast cancer tissue and bone mineral density.

Both bone and the breast are major target tissues of estrogen actions. The biological actions of estrogen depend on the interaction between estrogen and estrogen receptors (ER) in the target tissues. Therefore, ER concentration in tissues such as breast cancer might be associated with the amount of bone mass. The present study was aimed to examine whether there is a relationship between ER concentration in breast cancer tissue (ER-BCA) and bone mineral density (BMD). Forty-seven pre-menopausal and 34 post-menopausal women with newly diagnosed breast cancer were studied. The ER-BCA ranged from 0 to 339 fmol/mg cytosol protein (mean +/- SD = 68.6 +/- 97.0). Pearson's correlation analyses showed that ER-BCA negatively correlated to BMD of the spine (r = -0.251, p = 0.024), forearm (r = -0.341, p = 0.002), hip (r = -0.373, p = 0.001) and total body (r = -0.317, p = 0.004) in all 81 women. In 47 pre-menopausal women, the ER-BCA negatively correlated to the hip (r = -0.455, p = 0.001) and total body (r = -0.395, p = 0.006) but not to the spine and forearm BMD. Whereas, in 34 post-menopausal women, the ER-BCA negatively correlated to forearm BMD (r = -0.399, p = 0.019). Stepwise multiple regression analyses showed that the ER-BCA independently correlated to hip BMD in all 81 women (r = -0.373, p < 0.01) and in pre-menopausal women (r = -0.486, p < 0.001) and independently correlated to forearm BMD in post-menopausal women (r = -0.399, p < 0.05). The results of this study suggest that the presence of high estrogen receptor concentration in breast cancer tissue might induce a deleterious effect on bone mass particularly in pre-menopausal women.