Dose-dependent effect of AHPrBP in malignant hypercalcemia: wishful thinking and facts.
Explore the source record for details and available documents.
Diphosphonates↗
Biomedical subjects
P Burckhardt
Publications and source records attributed to P Burckhardt.
Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.
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.
Adult↗
Study of the 1 alpha-hydroxylation of 25-hydroxyvitamin D in phosphate diabetes.
Explore the source record for details and available documents.
Adult↗
[Therapeutic choices in osteoporosis].
Precise methods of evaluating bone density or bone quality (SPA, DPA, QCT, histomorphometry) have shown that various treatments for osteoporosis are efficient. Some drugs stimulate bone formation (NaF), others inhibit bone resorption (estrogens, calcitonin), while calcium and vitamin D act as additives. The drug is chosen which corrects the prevailing defect, which in turn can be suspected on the basis of a precise diagnosis. The latter is established by classification of the different forms of osteoporosis, based upon pathophysiological mechanisms. Apart from post-menopausal osteoporosis, which responds to estrogens, the other forms of high turnover osteoporosis may respond to calcitonin. Osteoporosis with low turnover, or age-related osteoporosis usually respond to NaF. Cyclic treatments set out to stimulate the maximum number of multicellular units of the bone. In this period of investigation and fruitful development, empiric treatment should give way to controlled cooperative studies.
Aged↗
Paget's disease of bone treated in five days with AHPrBP (APD) per Os.
Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 +/- 26 U/l (means +/- SEM) to 103 +/- 10 U/l after 6 months (nl less than 120 U/l). Urinary excretion of hydroxyproline decreased immediately and became normal (nl less than 2.3 mumol/lGF) as a mean at day 5 (from 4.6 +/- 0.4 mumol/lGF to 2.1 +/- 0.3 mumol/lGF). Thereafter it remained within the normal range (2.0 +/- 0.2 mumol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.
Aged↗
The effect of rectal and nasal administration of salmon calcitonin in normal subjects.
In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmon-calcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.
Administration, Intranasal↗
Effectiveness of salmon calcitonin administered as suppositories in tumor-induced hypercalcemia.
Although calcitonin is a natural, nontoxic, and rapid inhibitor of bone resorption, its use in the treatment of hypercalcemia is limited because of its transient efficacy and the need for repeated parenteral administration. In normal subjects, suppositories of calcitonin have been shown to be biologically active. Peak plasma concentrations of salmon calcitonin after rectal administration in six normal subjects were similar to those measured after parenteral administration. To evaluate the efficacy of calcitonin suppositories in disease states, 10 patients with moderate hypercalcemia due to malignancy were treated with salmon calcitonin, administered as suppositories containing 300 MRC units, three times a day for seven days. The mean plasma calcium level decreased significantly from 2.96 +/- 0.09 mmol/liter to 2.57 +/- 0.09 after one week (p less than 0.005) and rose again after discontinuation of treatment to 2.86 +/- 0.09 mmol/liter one week later. Urinary calcium and hydroxyproline values decreased during treatment and rose after discontinuation of treatment. The plasma calcium level decreased rapidly in six patients, becoming normal in five; three patients showed only a partial response, and one patient had no response at all. No side effects were observed, and clinical improvement was noted in nine of the 10 patients. Little or no response was observed in patients with extremely high urinary calcium or, to a lesser extent, high hydroxyproline excretion. There was a significant negative correlation between the maximal decrease in plasma calcium concentration and initial urinary calcium excretion (r -0.78, p less than 0.01). Thus, salmon calcitonin administered by the rectal route appears to be an easy, safe, and effective treatment of moderate hypercalcemia without apparent side effects.
Administration, Rectal↗
Dietary factors and medullary sponge kidneys as causes of the so-called idiopathic renal leak of calcium.
Out of 89 stone formers with idiopathic hypercalciuria, 51 remained hypercalciuric on a low calcium diet over 5 days: a renal leak of calcium could thus have been suspected in them. Dietary factors such as high sodium or high animal protein intake, and metabolic factors such as obesity with or without hyperinsulinemia, which all might account for the hypercalciuria of these patients, have been evaluated. This evaluation revealed conditions known to be associated with hypercalciuria in 37 of these 51 patients: 15 had hypercalciuria related to a high sodium intake, 7 had severe hyperuricosuria (greater than 1 g/24 h) reflecting a high animal protein intake, 20 were obese (greater than 120% of ideal weight) with (7 cases) or without (13 cases) concomitant high fasting plasma level of insulin (greater than 18 microU/ml). A careful retrospective analysis of the intravenous pyelograms disclosed medullary sponge kidneys in 8 cases which had remained undiagnosed so far. One of them was studied histologically. Only 14 out of 51 patients had an otherwise unexplained hypercalciuria on a low calcium diet. It is concluded that dietary causes appear to play a key role in 'idiopathic' hypercalciuria, that the incidence of a primary renal leak of calcium among idiopathic stone formers is much smaller than initially thought, and that this condition can hide unrecognized medullary sponge kidneys.
Calcium↗
Tubular dysfunction in nephrolithiasis: a consequence of the stone.
Explore the source record for details and available documents.
Acid-Base Equilibrium↗
[Intestinal absorption of calcium gluconate and oseine-mineral complex: an evaluation by conventional analyses].
Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Hypocalcemia and myelofibrosis: an unrecognized association].
Observation of a case of myelofibrosis with myeloid metaplasia of liver and spleen associated with hypocalcemia led us to investigate whether this association was fortuitous. We retrospectively analyzed the data of 30 patients with myelofibrosis and identified 9 patients with hypocalcemia out of 22 in whom the plasma calcium level corrected for serum protein could be obtained, i.e. a prevalence of hypocalcemia of 41%. The spleen was significantly larger in the patients with hypocalcemia than in those with normal plasma calcium level, suggesting that hypocalcemia was related to the duration of the disease. In 5 patients with hypocalcemia, biological and/or morphological evidence of osteomalacia was found. It is concluded that an association exists between myelofibrosis and hypocalcemia, possibly as a consequence of a disturbed vitamin D metabolism.
Aged↗
[Pyridoxine can normalize oxaluria in idiopathic renal lithiasis].
Pyridoxine (vitamin B6), given to patients with primary hyperoxaluria of type I, generally leads to a decrease in urinary excretion of oxalate owing to stimulation of conversion of glyoxylate to glycine instead of oxalate. It is not known, however, whether pyridoxine would equally influence hyperoxalurias of other origins, e.g. idiopathic or enteric. Two groups of patients were therefore given pyridoxine orally for 2 months (300 mg/d). Group 1 consisted of 10 idiopathic stone formers with mild hyperoxaluria of unknown origin. Group 2 consisted of 4 patients with enteric hyperoxaluria after intestinal bypass surgery. As a mean, enteric hyperoxaluria was not influenced by vitamin B6, which suggests that this disorder is the consequence of intestinal hyperabsorption of oxalate rather than of glyoxylate. In contrast, idiopathic hyperoxaluria was influenced by vitamin B6: urinary excretion of oxalate decreased in 8 patients out of 10 and became normal in 7. However, two patients did not respond to pyridoxine; both had concomitant severe hyperuricosuria (greater than 1 g/24 h), an observation suggesting that in these cases hyperoxaluria was of dietary origin. Four of the patients whose urinary excretion of oxalate became normal while on pyridoxine were followed up for 8 to 36 months after treatment: in all of them oxaluria remained normal. One whose oxaluria had returned to the upper normal limit was retreated after 2 years and again displayed a fall in urinary oxalate. It is concluded that pyridoxine given to idiopathic hyperoxalurics may correct the disorder, as in primary hyperoxaluria of type I; this is not the case in enteric hyperoxaluria. The mechanisms governing this sensitivity to vitamin B6 remain to be clarified.
Adult↗
[Paget's disease of bone treated per os with APD in 5 days].
Amino-hydroxy-propylidene bisphosphonic acid (APD) is a potent inhibitor of bone resorption. Its oral use in Paget's disease of bone has proved effective and safe when the drug is administered on a long-term basis. Since APD was found not to impair bone mineralization, it was assumed that a long remission would be obtained by administering a high dose of the compound over a very short period of time. Therefore, 12 patients with symptomatic Paget's disease received 1200 mg/d APD orally over 5 consecutive days. Follow-up is 2 months for all patients, 6 months for 6 patients and one year for one patient. Clinical improvement and biochemical remission were observed in all patients. Side effects were negligible (transient nausea in 2 patients and +1 degree C temperature increment noted for 2 days in 3 patients). Urinary hydroxyproline started decreasing within 2 days and became normal as a mean (+/- SEM) after 5 days (1.9 +/- 0.3 mumol/lGF, nl less than 2.3) and in all cases after 15 days. Thereafter it remained within the normal range (1.9 +/- 0.2 mumol/lGF) for 6 months. Plasma alkaline phosphatase activity fell progressively and significantly, and became normal after 1-3 months in all patients but one, a man with very active disease in whom the parameter remained slightly above normal and stable. At the end of the sixth month, mean plasma alkaline phosphatase activity was 100 +/- 13 U/l (nl less than 120 U/l). Plasma calcium and phosphate fell transiently between days 4 and 15.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
[Diagnosis, treatment and course of hypophyseal tumors. Retrospective study of 123 cases].
To assess the diagnostic and therapeutic problems associated with pituitary tumors, the clinical records of 123 consecutive patients presenting with radiological changes consistent with pituitary tumors were analyzed retrospectively. This diagnosis was established in 109 cases while the remaining 14 had other intrasellar pathologies. Prolactinoma in women was diagnosed at a significantly younger age (34.3 years) than in men (54.2 years) or than non-secreting adenoma in both sexes (52.1 years). In the two latter instances there was, on diagnosis, a larger proportion of visual field impairment due to tumor impingement on the visual pathway. Acromegaly was also recognized late, when skeletal changes were marked. The presence of certain symptoms could have suggested the diagnosis of pituitary tumor earlier in most cases. Surgical treatment was somewhat less effective in correcting hormone hypersecretion than in other series but, on the other hand, it caused less pituitary insufficiency and, thus, less additional discomfort to the patients. Hypopituitarism was frequent after transcranial surgery and radiotherapy (more than 50%) but was very rare after transsphenoidal tumorectomy. It appears that earlier diagnosis would result in less frequent visual impairment and hypopituitarism secondary to tumor extension and the necessary treatment.
Adrenocorticotropic Hormone↗
[Indication of the urinary citrate levels in idiopathic renal calculosis].
The reported incidence of hypocitraturia among stone formers (SF) varies between 15 and 50%. It is not known whether this incidence depends on the subtype of SF. The recent simplification of the method of measurement of U-citrate (Boehringer-Mannheim kit) led us to address this issue in 118 male idiopathic (I) SF, with either idiopathic hypercalciuria of the renal (n = 6), absorptive (n = 19) or dietary (n = 41) type, or with normocalciuria (n = 52). Results were compared with those of 42 normal male volunteers. 9 patients had hypocitraturia (less than 215 mg/24 h), all of whom belonged to the group of normocalciuric ISF; only this group of patients had mean U-citrate X V significantly lower than controls (p = 0.025). The cause of hypocitraturia in these patients remains unknown: there were no significant correlations between U-citrate X V and U-pH or blood HCO3 or Cl. Moreover, the patients with hypocitraturia had neither urinary infection nor signs of distal tubular acidification dysfunction as assessed by fasting morning urinary pH. Extended to our whole population of ISF (250 patients) 75% of whom have idiopathic stone disease, it appears that measurement of U-citrate decreased the number of ISF without detectable disorder from 34 to 26, i.e. to 10% of the whole population of stone formers. Since hypocitraturia can easily be corrected by oral administration of citrate, routine measurement of U-citrate in normocalciuric ISF appears a promising method.
Calcium↗
[Optimal dosage of chlorthalidone in the prevention of the recurrence of nephrolithiasis is 25 mg per day].
Thiazides are considered to be effective in preventing recurrence of various types of nephrolithiasis, but the optimum dosage has not been established. To address this issue, 5 idiopathic stone formers with hypercalciuria on low Ca diet received chlorthalidone (CT) in 3 different oral doses and were randomly assigned either to the sequence 25-50-100 mg/day or the reverse (2 months per dose, monthly blood and urine measurements). The anticalciuric effect of CT was significant only at 50 and 100 mg/day, at the expense of a dose-dependent decrease in U-citrate excretion. We also observed a dose-dependent decrease in blood levels of K, increases in those of HCO3 and urate, as well as in U-pH, a tendency for blood levels of Mg and U-oxalate excretion to fall, and no change in U-urate excretion. Therefore, to derive the optimal CT dose the Tiselius' risk index was applied, which is based on the values of urinary [Ca], [oxalate], [Mg], [citrate] and volume. CT produced a decrement in risk index which was similar at each of the doses tested. Thus, raising CT doses beyond 25 mg/day does not hold out the prospect of improved prophylaxis. This agrees with Ettinger's preliminary data (Urol. Res., 1984) showing a similar protective effect of CT at 25 and 50 mg/day despite the absence of a significant anticalciuric effect at 25 mg/day.
Calcium↗
[Diagnostic tests in parathyroid diseases].
The diagnosis of primary hyperparathyroidism (PHP) depends increasingly on laboratory tests, since the majority of patients are elderly people without typical symptoms. A mean plasma calcium level close to the upper normal limit serves to diagnose hypercalcemia. To rule out malignant disease, the most common cause of hypercalcemia, measurement of plasma PTH is the most appropriate test. Determination of blood phosphorus, chloride, and alkaline phosphatase, and of urinary calcium and phosphorus, contribute to the investigation of the metabolic effects of the given disease but are not very useful for causal diagnosis. Urinary and nephrogenous cyclic AMP reflect PTH secretion but can be elevated in paraneoplastic hypercalcemia. Diagnosis of subtle forms of PHP by dynamic tests is largely of scientific interest, since they do not necessarily need treatment. The diagnosis of hypoparathyroidism is primarily clinical. PTH measurements rarely distinguish normal from low values. In severe hypocalcemia of non-parathyroid origin, plasma PTH is elevated (except in hypomagnesemia). In borderline cases, measurement of urinary cyclic AMP or of plasma PTH after attempted stimulation by EDTA infusion is helpful, especially in distinguishing between subtle hypoparathyroidism and tetany induced by hyperventilation.
Adenoma↗
A single-day treatment of tumor-induced hypercalcemia by intravenous amino-hydroxypropylidene bisphosphonate.
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)
Adult↗