Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An initial clinical phase I trial of inosine dialdehyde has been carried out in 40 patients at dose levels of 30-4000 mg/m2 for 5 days given intravenously (iv) monthly. At 1.5 g/m2, noncumulative dose-related toxicity occurred in all patients which consisted of nausea and vomiting, local pain, alterations in coagulation mechanism, elevated partial thromboplastin time, and positive Coombs' test. No dose-limiting leukopenia, thrombocytopenia, anemia, or bleeding occurred; however, depression of the leukocyte and platelet counts, and decreased hemoglobin value were observed. The dose-limiting toxic effect was renal tubular damage with reversible acute renal failure in one of four patients who received 3000 mg/m2 iv for 5 days. Refractory hypercalcemia was controlled in three of three patients without tumor effect. Responses occurred in patients with seminoma, oat cell carcinoma, and melanoma. A starting dose of 2 g/m2 for 3 days monthly is recommended for phase II trials and a trial in lung carcinoma is now being conducted.
Cancer Chemother Rep
PMID:Clinical phase I trial of inosine dialdehyde (NSC-118994). 110 41

The presence of hypercalcemia in patients with known cancers may be due to the cancers themselves, or to co-existing primary hyperparathyroidism. The differentiation of primary hyperparathyroidism from the hypercalcemia of malignancy is important since the relief of distressing symptoms and prevention of hypercalcemic crises and renal failure can be accomplished relatively easily by parathyroid surgery in the former condition, and only with difficulty, at times, with fluids and drugs in the latter condition. The histories of three recent patients are presented, which demonstrate the difficulties inherent in the differentiation of these conditions. These patients were ultimately found at operation to have primary hyperparathyroidism in addition to malignancies of the cervix, adrenal gland and kidney. In our experience the following have been helpful in establishing a diagnosis; history of hypercalcemia prior to development of cancer, the type of cancer itself, the effect of cancer therapy on the hypercalcemia, and selective venous sampling with radioimmunoassay for parathyroid hormone.
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PMID:The differentiation of primary hyperparathyroidism from the hypercalcemia of malignancy. 111 56

The fascinating history of the first Memorial Hospital patient who was diagnosed as having hyperparathyroidism is reviewed. The illness presented as a cystic mass in a femur in 1929, which was treated with radiation. When the patient was first seen at Memorial Hospital in 1931, the diagnosis of osteitis fibrosa cystica was made; serum calcium was 14 mg/100 ml. In 1932, 6 years after Mandl performed the first parathyroidectomy ever for osteitis fibrosa cystica, this patient's neck was explored, and a right hemithyroidectomy was done, with removal of two normal parathyroid glands. The parathyroid tumor was finally located and partially removed in 1937 after a second failure at neck exploration in 1936. Correspondence between Dr. Edward D. Churchill at the Massachusetts General Hospital and Dr. Bradley Coley at Memorial Hospital indicated the concern at that time about uncontrollable tetany, which had been fatal in some contemporary cases and which had led to the practice of only partially removing the tumor. Following this, the patient was observed with documented hypercalcemia and chemical evidence of hyperparathyrodism until age 79. The physical and chemical abnormalities over the years up to and including her last exam are presented. The case is important not only from the historical viewpoint, but because it lends a perspective to long-term parathyroid disease, which is becoming less appreciated in this day of the routine serum calcium by SMA-12 screening. The question of partial parathyroidectomy for adenoma or hyperplasia is reviewed, and the question of observation of patients with mild hypercalcemia who probably have parathyroid tumors is discussed.
Cancer 1975 Mar
PMID:Documented hyperparathyroidism of thirty-six years' duration. 111 47

N-nitrosomethylurea (NMU) given intravenously to rats at age 50 days induced mammary carcinomas in 89% of BUF/N, 73% of Sprague-Dawley, and 89% of F344 females. Latent periods were, respectively, 77, 86, and 94 days. Mortality was negligible. Biologic properties of NMU-induced tumors were tested in the BUF/N inbred strain. Before treatment, it reduced the number of tumors per rat but not the incidence; and after the tumor was established, castration arrested tumor growth or caused a temporary regression of the tumor. Metastases to bone marrow and spleen were constant, but they were rare to the liver and lungs. After the primary tumor was removed, metastases continued to grow but at a slower rate than the growth of the primary tumor. Almost all tumors were transplantable intraperitoneally and/or subcutaneously in the inguinal area of intact as well as ovariectomized and adrenalectomized rats. Transplanted tumors were able to metastasize as were primary tumors. Doubling times of NMU-induced primary and transplanted carcinomas were similar to 7 days. Cachexia ensued at the 5th week from the onset of the first tumor. When the tumor was larger than 15 g, hypercalcemia was usually observed. The treatment described appears to be the simplest method for inducing in rats a most nearly complete model for human mammary carcinomas.
J Natl Cancer Inst 1975 Feb
PMID:N-nitrosomethylurea as mammary gland carcinogen in rats. 111 23

Hypercalcemia associated with nonmetastatic malignancy has been reported most frequently with lung or kidney tumors, while among gynecologic malignancies, the ovary has been the most common primary site. The pertinent clinicopathologic features of 2 cases of nonmetastatic vulvar carcinoma producing hypercalcemia are described in the present report. Including 3 previously reported cases, the vulva is seen to be the second most common site in the female genital tract for production of this paraendocrine syndrome. The clinician should be aware of the association of hypercalcemia and mental confusion with bulky vulvar tumors, so that surgery will not needlessly be delayed in a futile attempt to correct the hypercalcemia medically,
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PMID:Vulvar carcinoma with hypercalcemia. 111 57

Virtually any malignancy may lead to hypercalcemia, but carcinoma of the breast, myeloma, and carcinoma of the lung are especially frequent offenders. A more difficult diagnostic problem is posed by the "silent" tumor which secretes a substance causing hypercalcemia. Foremost in this category are bronchogenic carcimona and hypernephroma.
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PMID:Hypercalcemia and malignant disease. 111 72

Porcine or salmon calcitonin was given, as emergency treatment for 17 patients with hypercalcaemia, mostly of a severe degree. A lowering of serum calcium was achieved in all of 11 patients with primary hyperparathyroidism and in another 4 with malignancies. In most of the patients, the lowering of serum calcium level was accompanied by a pronounced clinical amelioration. This made possible successful parathyroidectomy without complications in the patients with primary hyperparathyroidism. In all patients except one, a decrease in serum creatinine was observed during treatment. Creatinine clearance was studied during calcitonin treatment in 2 patients and showed an increase. Calcitonin was ineffective in 2 of the patients with hypercalcaemia: one with plasmacell sarcoma of the lungs and another one with sarcoidosis. No serious side-effects were observed. Due to its quick action and lack of toxic effects, calcitonin is recommended when a prompt reduction of serum calcium is of vital importance.
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PMID:Acute treatment with calcitonin in primary hyperparathyroidism and severe hypercalcaemia of other origin. 117 65

The effect of certain disease parameters on remission and survial time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan-prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.
Cancer 1975 Oct
PMID:Prognostic factors in multiple myeloma. 117 23

A young male had an assumed dentigerous cyst marsupialized and later a recurrent ameloblastoma resected. Eleven years later he was admitted with renal stones and hypercalcemia and metastases of the ameloblastoma in the left lung were discovered. Death occurred as a result of spinal and hepatic spread of his tumor and thrombosis of the renal veins. Renal calcification was demonstrated. The possible causes of the hypercalcaemia which was not associated with a raised serum parathormone or affected by parathyroidectomy is discussed.
Cancer 1975 Dec
PMID:A metastasising ameloblastoma associated with renal calculi and hypercalcaemia. 120 77

The gene encoding PTH-related peptide (PTHrP) is expressed in a wide variety of normal and neoplastic tissues. Increased PTHrP gene expression in and secretion of PTHrP by specific tumors directly contributes to the development of malignancy-associated hypercalcemia in vivo. To define the genetic elements important for the control of PTHrP gene transcription, we used the reverse transcription polymerase chain reaction to delineate the control of promoter utilization and the splicing patterns of the exons encoding 5'-untranslated sequences. The majority of normal and neoplastic human tissues contained PTHrP mRNA transcripts initiating from both the up-stream (P1) and down-stream (P2) human PTHrP promoters. Furthermore, the downstream promoter was preferentially used by a factor of more than 30-fold. P1-initiated transcripts contained RNA species both with and without exon 2 (E2) sequences, except in the pancreas, adrenal, and stomach, where E2-containing sequences predominated. The transcriptional activities of P1, P2, and P1 + P2 were assessed by transfection of the corresponding PTHrP-chloramphenicol acetyltransferase (CAT) fusion genes into heterologous cell lines. Fusion genes containing P2 sequences were more transcriptionally active than fusion genes containing P1 sequences. The transcriptional activities of P1 + P2 in their natural tandem orientation were additive in rat keratinocytes and human JEG choriocarcinoma cells. In contrast, the activity of P1 + P2 was less than that of P2 alone in hamster BHK fibroblasts and InR1-G9 cells, and human HeLa cells. Analysis of the transcriptional properties of 5'-deleted human PTHrP-CAT constructs revealed the presence of multiple positive and negative DNA sequences (within both P1 and P2) functionally important for human PTHrP gene transcription. Distinct positive and negative DNA elements were also identified from analysis of 5'-deleted rat PTHrP-CAT fusion genes. The results of these experiments provide evidence for cell- and tissue-specific utilization of 1) distinct human PTHrP transcription start sites and specific patterns of 5'-exon splicing and 2) multiple positive and negative DNA control elements, important for the regulation of human and rat PTHrP gene transcription.
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PMID:Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements. 128 Mar 27


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