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ABSTRACT: Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean +/- SEM) 0.8 +/- 0.2 pmol/l in the first trimester to 2.7 +/- 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 +/- 8 U/l (first trimester) to 347 +/- 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 +/- 0.2 pmol/l (first trimester) to 3.1 +/- 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 +/- 0.05 nmol/l from 0.19 +/- 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 +/- 0.11 (first trimester) to a nadir of 0.19 +/- 0.04 6 weeks postpartum (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
European Journal of Endocrinology 11/1994; 131(4):369-74. · 3.42 Impact Factor
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ABSTRACT: In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n = 13), 45 mg (n = 9), and 90 mg (n = 13) in an attempt to see what factors influenced the response of serum calcium to pamidronate. The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into "good" and "poor" responders depending on whether a normal serum calcium was obtained. Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r = 0.45, P = 0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean +/- SEM): 65.0 +/- 9.4 nmol/liter GF (poor responders) versus 29.6 +/- 6.3 (good responders), P = 0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r = -0.41, P = 0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF +/- 0.09 (poor responders) versus 0.76 mmol/liter GF +/- 0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcified Tissue International 01/1993; 51(6):419-23. · 2.38 Impact Factor
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ABSTRACT: Pamidronate has been demonstrated to be an effective agent in the treatment of cancer-associated hypercalcaemia. The dose regime, however, remains controversial. In this study 16 patients with cancer-associated hypercalcaemia were given 30 mg pamidronate by intravenous infusion and 16 were given 90 mg also by infusion. Groups were well-matched in terms of tumour types, bone metastases, pre-treatment serum calcium and creatinine, fasting urinary calcium/creatinine ratio, nephrogenous cAMP and the renal tubular threshold for phosphate reabsorption (TmPO4). The calcium lowering effect was similar in both treatment groups with nadir at day 6 of mean (+/- SEM) 2.48 mmol/l (+/- 0.06) in the 30 mg group and at day 9 in the 90 mg group of 2.51 mmol/l (+/- 0.03) (P less than 0.01). 10 patients in the 30 mg group and 8 in the 90 mg group were normocalcaemic at this point. Similarly when those patients with more severe hypercalcaemia (greater than 3.30 mmol/l, n = 7 in each group) were analysed separately, no significant difference was evident between the two groups. Urinary calcium/creatinine ratios fell to a nadir at day 6 in both groups of 0.33 (+/- 0.05) (30 mg group) and 0.37 (+/- 0.10) (90 mg group) (P less than 0.01). Follow-up results after the initial 9 days showed the mean time to relapse to be 38 days (range 18-90) in the 30 mg group and 34 days (11-105) in the 90 mg group.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone and Mineral 01/1992; 15(3):249-56.
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ABSTRACT: Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome.
Postgraduate Medical Journal 12/1990; 66(781):918-22. · 1.94 Impact Factor
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The Lancet 04/1990; 335(8691):737. · 38.28 Impact Factor
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ABSTRACT: Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.
The Lancet 12/1989; 2(8673):1180-2. · 38.28 Impact Factor
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The Lancet 08/1988; 2(8605):277. · 38.28 Impact Factor
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The Lancet 07/1987; 1(8547):1428. · 38.28 Impact Factor
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ABSTRACT: The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.
Journal of Clinical Pathology 07/1986; 39(6):641-6. · 2.31 Impact Factor
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ABSTRACT: We have tested the accuracy, acceptability and general performance of three recently-marketed samplers for arterial blood gas measurement (the Corning Arterial Blood Sampler, the Concord 'Pulsator' and the Sarstedt 'Monovette'). All three greatly reduce or eliminate the error of venous sampling, and the Corning and Sarstedt samplers eliminate the risk of dilution of the sample by excess heparin solution. A positive bias in pO2 measurement, more marked at higher levels, was demonstrated with the Concord and Sarstedt samplers, and the latter carry a slightly increased risk of cross-infection. None of the samplers completely overcame potential sampling errors.
Annals of Clinical Biochemistry 06/1986; 23 ( Pt 3):329-33. · 2.17 Impact Factor
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Archives of Internal Medicine 04/1986; 146(3):607-8. · 11.46 Impact Factor
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ABSTRACT: Several aspects of calcium metabolism were studied in five patients during the surgical exploration of malignant tumours associated with humorally-mediated hypercalcaemia. Before operation in all patients the renal tubular threshold for calcium reabsorption was raised and the threshold for renal tubular phosphate reabsorption depressed. On removal of the primary tumour in three cases, serum calcium returned to normal, renal calcium threshold fell, renal phosphate threshold rose, but urinary hydroxyproline excretion did not change. In two patients where the tumour proved inoperable, serum calcium remained elevated and no changes in renal calcium threshold or phosphate threshold occurred. Histomorphometry carried out on biopsy specimens from four patients showed normal bone resorption in three, and slightly increased resorption in one, without depression of osteoblastic bone formation. It is suggested that hypercalcaemia in these patients resulted mainly from an alteration in renal calcium threshold caused by a humoral substance released by tumour cells. Correction of hypercalcaemia on removal of the primary tumour was achieved rapidly and could be explained principally by a reduction in renal calcium threshold with increased loss of calcium into the urine. These data contrast with those of many previous studies which have emphasised the predominant role of accelerated osteoclastic bone resorption as the principal cause of hypercalcaemia in malignancy and suggest that a renal effect of the putative humoral agent may predominate in some cases.
The Quarterly journal of medicine 04/1986; 58(227):325-35.
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British medical journal (Clinical research ed.) 03/1986; 292(6517):410.
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ABSTRACT: Thirty-nine patients with cancer-associated hypercalcaemia were randomly allocated to receive aminohydroxypropylidene diphosphonate (APD), mithramycin, or corticosteroids and salmon calcitonin. Corticosteroids/calcitonin had the fastest calcium-lowering effect, owing mainly to an acute reduction in renal tubular calcium reabsorption; continued therapy over 9 days failed to suppress accelerated bone resorption, however, and most patients remained hypercalcaemic. Mithramycin also substantially reduced serum calcium within 24 h. A further dose on day 2 generally controlled hypercalcaemia until day 6 by reducing both bone resorption and renal tubular calcium reabsorption. By day 9, however, about 50% of the mithramycin-treated patients had started to relapse as bone resorption increased again. With APD serum calcium levels fell more slowly but progressively owing to effective suppression of bone resorption; by day 9 the control of hypercalcaemia was significantly better than in the other treatment groups. Symptoms of hypercalcaemia were greatly relieved, especially by APD.
The Lancet 11/1985; 2(8461):907-10. · 38.28 Impact Factor
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The Lancet 05/1985; 1(8433):878. · 38.28 Impact Factor
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ABSTRACT: The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.
Clinical Science 03/1984; 66(2):187-91. · 4.61 Impact Factor
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British medical journal (Clinical research ed.) 11/1983; 287(6399):1131-2.
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ABSTRACT: The algorithms used in this hospital to assess calcium status are calculated ionised serum calcium and the serum calcium concentration adjusted for albumin. In order to establish their clinical usefulness, they were compared with the ionised calcium concentration measured on the Nova 2 instrument in patients with various calcium and protein abnormalities. Good correlation was found between the measured and calculated values. The predictive values for the calculated results and for total serum calcium concentrations are presented. In this series, the derived values were useful in predicting the serum ionised calcium concentration of the patients studied.
Annals of Clinical Biochemistry 04/1981; 18 (Pt 2):106-9. · 2.17 Impact Factor
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ABSTRACT: A simple procedure is described for the preparation of a stable precision quality control material for use in the measurement of level of ionised calcium in serum at or near the reference range. Repeat analyses on a Nova 2 ionised calcium analyser of serum pools stored at different temperatures over a period of three months showed coefficients of variation less of less than 4%.
Annals of Clinical Biochemistry 04/1981; 18 (Pt 2):110-1. · 2.17 Impact Factor
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The Lancet 03/1981; 1(8216):385. · 38.28 Impact Factor
