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S J Gallacher

Publications and source records attributed to S J Gallacher.

At least 19 recordsLinked to original sources
PubMed1992

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy.

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)

Absorption↗
PubMed1992

Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study.

BACKGROUND: Bisphosphonates have been shown to be effective agents in the treatment of postmenopausal osteoporosis. Because corticosteroid associated osteoporosis is often associated with increased bone turnover, the effect of intermittent intravenous infusions of pamidronate on this condition has been investigated. METHODS: Seventeen patients (five male) with chronic corticosteroid dependent lung disease (15 asthma, two sarcoidosis) were treated with infusions of 30 mg pamidronate once every three months for one year. These patients had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary hydroxyproline: creatinine ratio at the same time as densitometry and radiography were performed. RESULTS: Pretreatment density of L2-4 and the neck of the femur was significantly lower in these patients compared with a cohort of 100 age and sex matched controls (L2-4 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary hydroxyproline:creatinine ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in L2-4 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur. CONCLUSIONS: Intermittent infusions of intravenous pamidronate would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced osteoporosis associated with chronic lung disease. Longer term controlled studies are indicated.

Adult↗
PubMed1991

Failure to detect paramyxovirus sequences in Paget's disease of bone using the polymerase chain reaction.

It is widely believed that Paget's disease of bone is due to a "slow virus" infection of osteoclasts with one of the paramyxovirus group. Controversy continues to surround the identity of the virus involved, however, since at different times evidence has been presented implicating measles virus (MV), respiratory syncytial virus (RSV), and canine distemper virus (CDV) as putative infective agents. In this study we used the technique of reverse transcription and polymerase chain reaction (PCR) to screen for paramyxovirus sequences in ribonucleic acid (RNA) extracted from pagetic bone. We were able to detect viral amplification products of the appropriate size in RNA extracted from as few as 50 cells experimentally infected with a wide range of paramyxoviruses, including measles, canine distemper, parainfluenza 3, and respiratory syncytial virus, but we found no evidence of viral products in RNA extracts of affected bone from 10 consecutive patients with Paget's disease. This study fails to support the hypothesis that active infection with one of these or a related paramyxovirus is involved in the pathogenesis of Paget's disease.

Aged↗
PubMed1991

Direct and indirect assessment of the parathyroid hormone response to pamidronate therapy in Paget's disease of bone and hypercalcaemia of malignancy.

In patients with either Paget's disease or hypercalcaemia associated with malignancy (HCM) we have assessed the parathyroid response to pamidronate therapy, both by immunoassay of serum intact parathyroid hormone PTH (1-84) and by measurement of indirect parameters of PTH bioactivity, tubular maximum reabsorption of phosphate (TmPO4/GFR) and nephrogenous cyclic AMP (NcAMP). In 12 patients with Paget's disease, therapy with pamidronate produced a small but significant decrease in adjusted serum calcium within the reference interval which was accompanied by a progressive increase in PTH (1-84) secretion and a corresponding fall in TmPO4/GFR and increase in NcAMP. In 12 patients with HCM pretreatment, PTH (1-84) concentrations were suppressed, whilst mean TmPO4/GFR was reduced and NcAMP was increased, compatible in most patients, with parathyroid hormone-related peptide (PTHrP) driven hypercalcaemia. Therapy with pamidronate produced the expected fall in serum calcium but caused an increase in PTH (1-84) secretion in the presence of absolute hypercalcaemia. The initial subnormal TmPO4/GFR decreased further to a nadir on day 5, and there was a corresponding further increase in NcAMP. By day 7, however, when PTH (1-84) concentrations were maximal, there was a significant paradoxical rise in TmPO4/GFR and a corresponding decrease in NcAMP. These data are consistent with a variable trigger point for PTH (1-84) secretion, one consequence of which is a reduction in the risk of hypocalcaemia following pamidronate. The results have major clinical implications for the interpretation of PTH (1-84) measurements in patients who are being treated or about to be treated for bone disease or for hypercalcaemia of malignancy (HCM).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia.

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)

Calcium↗
PubMed1991

Augmentation of parathyroid 201Tl/99Tcm scanning by infusion of trisodium edetate.

A significant number of patients with primary hyperparathyroidism have negative preoperative 201Tl/99Tcm subtraction localization scans. In this study an attempt was made to improve scan localization by creating a period of relative hypocalcaemia and increased parathyroid hormone (PTH) secretion before scanning. Six patients with primary hyperparathyroidism were studied (mean serum calcium 2.80 mmol l-1; range 2.70-2.95). All had had a negative standard 201Tl/99Tcm scan carried out within the 6 months prior to this study. Patients were commenced on an intravenous infusion of the calcium chelating agent trisodium edetate at a dose of 24 mg kg-1 h-1 given in 500 ml 0.9% saline over 90 min. Immediately thereafter a 201Tl/99Tcm scan was carried out in the usual way. Three patients showed areas of discordant thallium uptake consistent with the presence of a parathyroid adenoma. Two of these patients had surgery and an adenoma was found at the site corresponding to the scan appearances. It would appear that creating relative hypocalcaemia and increasing PTH secretion may allow increased thallium uptake, possibly secondary to the increased cellular metabolic activity, and thus creating a positive scan.

Adenoma↗
PubMed1991

Clinical experience with pamidronate in the treatment of Paget's disease of bone.

Bisphosphonates have been shown to be effective in treating the increased bone turnover associated with Paget's disease of bone. In this study two groups of patients were treated with pamidronate by intravenous infusion. In group 1 (n = 15) 30 mg of pamidronate was given once a week for six weeks. A subgroup (group 1A, n = 6) of more severely affected patients (pretreatment serum alkaline phosphatase (ALP) greater than 1000 U/l, normal range 80-280 U/l) received a further 60 mg weekly for three weeks. Group 2 (n = 24) received 45 mg of pamidronate every three months for one year. In both groups the level of ALP in serum samples decreased steadily throughout the year. In group 1 the level decreased to a mean value of 230 U/l (95% confidence interval 188-281) and in group 2 to 297 U/l (227-389). Four of the six patients in group 1A achieved normal ALP, whereas ALP remained at an increased level in all of the 10 patients in group 2 whose pretreatment ALP was greater than 1000 U/l, suggesting that a dose-response effect exists. The lowest hydroxyproline to creatinine ratios (normal ratio less than 0.033) were observed at the end of treatment in group 1, with a mean ratio of 0.022 (range 0.015-0.033) and at three months after the start of treatment in group 2 with a mean ratio of 0.029 (range 0.022-0.037). There was a significant decrease in the turnover of bone, as measured by whole body retention of radiolabelled bisphosphonate, from a mean of 49.3 to 41.0% (p less than 0.01). These data confirm that pamidronate is effective in the management of Paget's disease of bone. For patients with levels of ALP in serum samples of up to four times above the upper limit of the normal reference range, an effective and convenient regimen is 45 mg every three months for one year. For patients with higher levels of ALP higher doses may be more effective.

Adult↗
PubMed1991

Pseudogout associated with the use of cyclical etidronate therapy.

Recently the use of etidronate in a cyclical fashion has been shown to be of value in the treatment of osteoporosis. Like all bisphosphonates etidronate is structurally similar to pyrophosphate, further it is also known to interfere with phosphate handling by the kidney resulting in elevated plasma phosphate levels. This report describes the case of a patient with established osteoporosis who developed pseudogout associated with cyclical etidronate use. The possible mechanism responsible for this is discussed.

Aged↗
PubMed1990

Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patients.

STUDY OBJECTIVE: To review the effects of antihypercalcemic treatment on morbidity and mortality in cancer-associated hypercalcemia. DESIGN: Retrospective study of 126 consecutive patients with cancer-associated hypercalcemia. SETTING: Inpatient referrals from a teaching hospital in the United Kingdom. INTERVENTION: Medical antihypercalcemic therapy supplemented by specific anticancer therapy where possible. MEASUREMENTS AND MAIN RESULTS: Median survival was 30 days. Survival did not differ in patients treated with different antihypercalcemic regimens but was longer (median, 135 days; P less than 0.001) in a subgroup of 26 patients for whom specific anticancer therapy was available. Polyuria and polydipsia improved after therapy in 83% of cases, central nervous system symptoms in 71%, constipation in 70%, nausea and vomiting in 56%, anorexia in 50%, and malaise and fatigue in 47% (all significant, P less than 0.001, pre-treatment compared with post-treatment). Pain control improved in only 23% of cases (not significant). Only 7% of patients with post-treatment serum calcium values above 3.50 mmol/L improved clinically compared with 80% whose calcium values fell below 2.80 mmol/L (P less than 0.001). Corresponding figures for the proportion of patients discharged from the hospital were 0% and 68% (P less than 0.001). CONCLUSIONS: Life expectancy is poor in cancer-associated hypercalcemia even in patients who are actively treated. Antihypercalcemic therapy has an important palliative role, however, because symptoms are usually improved and, in many cases, patients may be made well enough to be discharged from the hospital during the terminal stages of their illness.

Adolescent↗
PubMed1990

The loss of circadian rhythm for intact parathyroid hormone and nephrogenous cyclic AMP in patients with primary hyperparathyroidism.

The measurement of serum intact parathyroid hormone (PTH) (1-84) over a 24-h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N-cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1-84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1-84) secretion.

Adult↗
PubMed1990

Immobilization-related hypercalcaemia--a possible novel mechanism and response to pamidronate.

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.

Adult↗
PubMed1990

Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling.

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.

Biomarkers↗
PubMed1990

Serial bone scans in Paget's disease: development of new lesions, natural variation in lesion intensity and nature of changes seen after treatment.

Serial radionuclide bone scans (n = 96) of 40 patients with Paget's disease were studied and tracer uptake graded using a four-point subjective scale. In nine patients studied without treatment the serial scan appearance improved in some, remained unchanged in others and deteriorated in yet others. Similarly individual lesions demonstrated increased, decreased or unchanged tracer uptake. One lesion disappeared without treatment but no new lesions developed. After treatment with aminohydroxypropylidene bisphosphonate (APD) or ethanehydroxy bisphosphonate (EHDP) the overall scan appearance improved in the majority of patients treated (n = 34), but individual lesions demonstrated increased (n = 20), unchanged (n = 79) or decreased uptake (n = 86). The mean reduction in tracer was 32% and 20 lesions reverted to normal intensity. The site of the lesion or the initial intensity of tracer uptake did not influence response to therapy. New lesions developed in five patients after therapy. There was variable correspondence between scintigraphic changes and biochemical parameters of response. From our study we conclude that serial bone scans must be used with caution when interpreting the response of Paget's disease to therapy.

Aged↗
PubMed1989

Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia.

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.

Administration, Oral↗