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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hypercalcemia is caused by both increased bone resorption and enhanced tubular reabsorption of calcium. First, the response to an infusion of APD was compared in two groups of patients: 23 with breast cancer versus 20 with squamous cell cancer. The decrease in plasma calcium was smaller in the latter group (p less than 0.05 at day 14), due to increased tubular reabsorption of calcium (TmCa/GFR 2.20 +/- 0.05 versus 2.58 +/- 0.06 mmol/liter; p less than 0.001), whereas the degree of bone resorption reflected by urinary hydroxyproline was identical. Therefore, at a given initial plasma calcium level, the type of tumor (on which TmCA/GFR depends) seems to be a determinant for the effectiveness of the treatment. Second, the response to the initial treatment was compared with that to a second treatment with the same dose in 12 patients whose malignant hypercalcemia relapsed. Within 9 days, plasma calcium decreased from 3.46 +/- 0.10 to 2.50 +/- 0.10 mmol/liter after the first course, but only from 3.37 +/- 0.08 to 2.79 +/- 0.09 mmol/liter after the second course (p less than 0.01). TmCa/GFR was similar before the first and the second treatment and did not vary during the days following the infusion of APD. Initial urinary hydroxyproline was slightly but not significantly higher before the second treatment. It dropped following both APD courses, but to a lesser extent after the second treatment, reflecting higher bone resorption or possible resistance to bisphosphonate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response to retreatment of malignant hypercalcemia with the bisphosphonate AHPrBP (APD): respective role of kidney and bone. 233 80

Severe acute hypercalcemia (4.03 mmol/l) developed in a 50 years old woman after head and intraabdominal trauma (and splenectomy). After failure to correct the calcium levels by intravenous saline, furosemide, steroids and calcitonin, two hemodialyses were performed; definitive control of hypercalcemia was obtained by intravenous (3-amino-1-hydroxypropylidene)-1.1-bisphosphonic acid (APD). APD is a new drug analog of pyrophosphate; its main property is to block bone resorption, irrespective of its stimulus. As suspected by clinical and laboratory data and confirmed by arteriographic findings, surgery and pathologic examination, the underlying pathology was a mild primary hyperparathyroidism which was acutely worsened (parathyroid crisis) in the course of the trauma. Definitive treatment consisted of the removal of the adenoma responsible of the hyperparathyroidism.
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PMID:Posttraumatic parathyroid crisis and severe hypercalcemia treated with intravenous bisphosphonate (APD). Case report. 236 Mar 92

The effect of long-term bisphosphonate (APD) treatment on the morbidity from bone metastases in breast cancer patients was studied in a controlled clinical trial. 131 patients were randomized between treatment with APD (300 mg/day orally) or control. Systemic treatment for breast cancer was left to the discretion of the physician. The distribution of cases according to age, receptor status and previous treatment was similar in both groups. Patients were examined at 3-month intervals, while bone scans and radiography of relevant lesions in the skeleton were performed every 6 months. After a median follow-up of 13 months, the morbidity in the treated group was significantly less than in the controls. This concerned the occurrence of hypercalcemia, bone pain and fractures, and the need for radiotherapy of osteolytic lesions. In this interim analysis, APD treatment more than halved the requirement for specific treatment of bone lesions. The treatment is simple and well tolerated at a relatively low dosage. A higher oral dose was precluded due to gastrointestinal toxicity. Because the effect of APD on skeletal morbidity was not complete, efforts should be made to develop more effective and less toxic bisphosphonates.
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PMID:Effect of long-term bisphosphonate treatment on morbidity due to bone metastases in breast cancer patients. 266 67

Bisphosphonates, associated with rehydration, became the treatment of choice of malignant hypercalcemia when it became apparent that these compounds normalized plasma calcium in most cases within a few days and with almost no side effects, and that their effect was prolonged. Dichloromethylene bisphosphonate and aminobisphosphonate, especially APD, were shown to inhibit bone resorption with no noticeable inhibition of bone formation, and were highly effective in the long-term treatment of Paget's disease. APD was used in almost 300 patients with malignant hypercalcemia published in the literature and has been used in the medical clinic at Lausanne for several years. When given to 14 patients with malignant hypercalcemia at the dose of 25 mg/day until plasma calcium became normal for two consecutive days, APD had to be given for 4-11 days, severe hypercalcemia needing longer treatment than mild hypercalcemia (Adami et al. 1982). When given for a fixed period of 6 days, again plasma calcium normalized in all patients, whether APD was given i.v. (30 mg/day, ten patients) or orally (1200 mg/day, ten patients) (Adami et al. 1985). Further shortening of the treatment to one single infusion given over 24 h did not decrease the efficacy, as long as high enough doses were given (Blomqvist 1986). For severe hypercalcemia of above 3.5 mmol/liter 60-90 mg had to be given, while 30-45 mg was sufficient in milder cases (Body 1984). Otherwise, mild, transient, and asymptomatic hypocalcemia could occur. Normalization of plasma calcium went along with clinical improvement, sometimes even with correction of coma. Renal function was improved, even when the initial plasma creatinine levels were up to twice normal. Hypercalcemia could reoccur, but the duration of the effect of APD (1 week to several months) depended among other things on the dose administered. The decrease in plasma calcium was accompanied by a decrease in urinary calcium and hydroxyproline, both showing inhibition of bone resorption. In the case of recurrency, the treatment could be repeated with almost unaltered efficacy, except in end-stage cancer disease. When given to 13 normocalcemic patients with bone metastases from breast cancer, hydroxyproline and urinary calcium again decreased. Bone pains and radiologic signs of metastatic bone resorption also showed significant improvement, although these latter effects could also be explained by the antitumoral treatment, in this uncontrolled open trial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Treatment of tumor-induced osteolysis by APD. 276 65

A case of chronic osteomyelitis complicated by the development of squamous cell carcinoma in the sinus tract is described. This complication was itself associated with the development of humoral hypercalcemia of malignancy, a phenomenon not previously described in this context. Common misconceptions relating to the interpretation of serum parathyroid hormone levels led to the misdiagnosis of hyperparathyroidism and parathyroid exploration. Forced saline diuresis, mithramycin and oral phosphate supplements were not able to provide long-term control of the hypercalcemia but the patient was subsequently managed successfully with intravenous (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and resection of the causative tumour.
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PMID:Hypercalcemia and squamous cell carcinoma complicating chronic osteomyelitis. 278 87

The search into the way in which skeletal metastases develops has not only shown that there are several mechanisms for the progressive bone destruction and bone formation that occur simultaneously in the majority of skeletal metastases, but also that an understanding of these basic mechanisms has significant therapeutic implications. Our results have shown that there are two main mechanisms for the bone formation: stromal bone formation and reactive bone formation. The former occurs in tumours which tend to be acellular, with a large fibrous stroma, whereas the latter occurs in virtually all metastases. There is no difference in the basic pathological process of sclerotic or lytic metastases, the radiographic appearance purely indicating the net balance between the different types of bone formation and the simultaneous progressive bone destruction. An understanding of the pathophysiological response to skeletal metastases explains why skeletal scintigraphy can be used to diagnose these lesions and the different mechanisms underlying the 'three-phase scintigram'. The first phase indicates the vascularity of the lesion; the second phase or 'blood-pool' image indicates the concentration in the extracellular fluid and the third phase or 'skeletal or delayed image' indicates the uptake in the reactive new bone. The secretion of an osteoblast inhibiting factor by myeloma indicates why there is no reactive bone produced by the majority of lesions in the absence of a fracture, and why scintigraphy is less reliable than plain radiographs for the detection of the lesions. There are two main mechanisms for the bone destruction, the most important being mediated via osteoclasts. An understanding of the humoral mechanisms stimulating the osteoclast proliferation may lead to more effective treatment of malignant hypercalcaemia and lytic metastases. Early results of use of APD are encouraging, and our results also suggest that clinical trials should be established to evaluate the effect of combination therapy with APD or prostaglandin inhibitor combined with the agents normally used in the management of patients with disseminated mammary carcinoma. The development of treatments to inhibit tumour-induced osteolysis will minimise the complications of pathological fracture, spinal instability, etc., and even if these treatments do not affect the primary tumour, its ability to metastasize, or the patient's survival, such treatment will be a major advance in the management of patients with carcinoma, because of the significant morbidity currently associated with the development of skeletal metastases and their complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The development of skeletal metastases. 279 40

The case history of a 26 year old woman describes the occurrence of a primary cholangiocarcinoma in the woman's liver during her 1st pregnancy with no signs of skeletal metastasis. During the previous 8 years, she had taken oral contraceptives (Microgynon 50). The case was successfully treated with chemotherapy (treatment with APD) and surgical removal of the tumor. It was considered highly unusual since malignant tumors of the liver occur seldom in the West, and very seldom among young people. Most patients are over 50; the illness strikes nearly twice as often in men as women. A tumor occurs in a cirrhotic liver in about 75% of cases; and, indications reveal that persistent hepatitis B plays a role in the development of hepatocellular carcinomas. The patient did not fit into any of the those categories. The patient's initial complaints occurred during her pregnancy. Previous medical literature has described patients with a malignant tumor of the liver during pregnany, and since 1970, many articles have shown a relationship between hepatic dysfunctions in women and the use of oral contraceptives. The benign dysfunctions usually involved liver cell edema and focalized nodular hyperplasia. Malignant liver tumors in such patients have been less frequently described in the literature; thus, their relationship with the use of oral contraceptives is less certain. Artlcles have appeared, however, indicating a connection between liver malignancy and the use of sex hormones. There are also indications that humoral hypercalcemia is a frequent finding in primary liver cancer.
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PMID:[A young woman with a liver tumor and hypercalcemia]. 302 Apr 47

40 patients with malignant hypercalcemia were treated with a single dose of APD, a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose response in man, the patients were divided into four groups receiving 30, 45, 60 or 90 mg respectively as 24-hour infusion. Initial plasma calcium was similar in all groups except that receiving 90 mg, some of whose patients had higher initial values. All patients responded to APD with a rapid decrease of plasma calcium concentration from 3.44 +/- 0.10 mmol/l at day 0 to 2.33 +/- 0.06 at day 6, p less than 0.001). Plasma calcium became normal within 4 to 6 days in all patients but 6, all from the group receiving the low doses of APD (30 or 45 mg). Slight and asymptomatic hypocalcemia occurred in only 2 patients of the low dose groups, but in 6 of the high dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 2 months in 6 patients of group 30 mg, in 5 patients of group 45 mg, in 1 patient of group 60 mg and in 2 patients of group 90 mg, whereas mortality was almost identical in the 4 groups. When retreated with a single dose of APD, all patients again showed normalization of calcemia. In all groups plasma phosphate, plasma creatinine and urinary calcium excretion decreased significantly. Clinical improvement was observed in all patients, with minimal side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of neoplastic hypercalcemia using single-infusion diphosphonate]. 334 11

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.
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PMID:Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP. 336 84

Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 +/- 0.14 to 2.24 +/- 0.06 mmol/liter in group A (p less than .001), but only from 3.22 +/- 0.15 to 2.49 +/- 0.10 mmol/liter in group B (p less than .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p less than .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p less than .01) to values slightly below the normal range from days 4 to 6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A single-day treatment of tumor-induced hypercalcemia by intravenous amino-hydroxypropylidene bisphosphonate. 350 61


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