PTH(1-84) in hypercalcaemia of malignancy.
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Humans↗
Biomedical subjects
W D Fraser
Publications and source records attributed to W D Fraser.
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↗
Amniotomy and maternal position in labor.
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Amnion↗
Thyroid function tests are rarely abnormal in patients with severe hyperemesis gravidarum.
OBJECTIVES: There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls. MEASUREMENTS: Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured. RESULTS: While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients. DISCUSSION: None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.
Antibodies↗
Differences between obstetricians in caesarean section rates and the management of labour.
OBJECTIVE: To determine if interobstetrician variation in caesarean section rates was associated with different approaches to the management of labour. DESIGN: A retrospective cohort study. SETTING: A tertiary care teaching hospital in Quebec, Canada. SUBJECTS: 546 nulliparae in spontaneous labour at term were grouped according to the rate of caesarean sections for dystocia of their obstetrician (high: women of two obstetricians with rates of 13.2% and 15.0%; and low: women of three obstetricians with rates of 6.0%, 6.2% and 6.5%). MAIN OUTCOME MEASURES: Frequency and timing of oxytocin, epidural, amniotomy, forceps. SECONDARY OUTCOME MEASURES: Indicators of neonatal asphyxia and trauma. RESULTS: No difference between groups was observed in the frequency or timing of use of oxytocin or epidural analgesia. Amniotomy was practised earlier by the obstetricians in the high group. Differences in section rates for dystocia were greatest in the second stage (low-2.4%, high-7.9%). Obstetricians in the low group intervened earlier with forceps or vacuum extractor. Nine babies (all in the low group), 8 of whom had had an instrumental vaginal delivery, suffered trauma (5 clavicular fractures, 4 facial palsies) (Fisher's exact test, P = 0.0139). CONCLUSION: The practice patterns of the two groups are distinguished by differences in management of the second stage. Although lower section rates were associated with an increase in mild neonatal trauma, this appears to have been mediated by the earlier use of forceps in this group.
Adult↗
Sleep shift dissociates the nocturnal peaks of parathyroid hormone (1-84), nephrogenous cyclic adenosine monophosphate, and prolactin in normal men.
The secretion of PTH(1-84) and PRL over a 24-h period in normal subjects has been shown to be highly correlated, with changes in PRL occurring approximately 2 h after those in PTH(1-84). It has been postulated that there may be neuroendocrine control common to PTH(1-84) and PRL. As the secretion of PRL is known to be strongly influenced by sleep we investigated the effect of a 7-h acute sleep shift on the nocturnal secretion of PTH(1-84), PRL, and nephrogenous cAMP, a marker of PTH(1-84) bioactivity. Six normal male subjects were studied on two occasions (study A sleep, 0100-0800 h; study B, 0800-1400 h) with samples withdrawn at 30-min intervals. Sleep shift produced the expected shift in PRL secretion to new time of sleep. The overall timing of the PTH(1-84) nocturnal peak (0200-0600 h) was not altered by sleep shift. However, the start of the rise in PTH(1-84) (0200-0300 h) was blunted (P less than 0.05), and the peak of nephrogenous cAMP, coincident with the nocturnal rise in PTH(1-84) in study A, was markedly attenuated (P less than 0.01). Thus whereas the results of this study argue against a direct neuroendocrine link between PTH(1-84) and PRL, it is postulated that sleep shift disrupts a high degree of temporal organization which, under normal conditions, may allow concerted metabolic effects between PTH(1-84) and other hormones over a 24-h period.
Adult↗
[Prediction of pre-eclampsia: ambulatory arterial hypertension].
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Circadian Rhythm↗
Cardiovascular responses to positive pressure breathing using the tactical life support system.
The improved protection afforded by the Tactical Life Support System (TLSS) vs. other partial pressure ensembles has not been reported with respect to the cardiovascular effects of positive pressure breathing (PPB). Nine seated subjects wearing TLSS were exposed to 30, 50, and 70 mm Hg PPB (breathing air) with four times this pressure in the G-suit. Experiments were conducted at ground-level in order, separated by 4 min rest and preceded by a 1-min control period. Stroke volume and cardiac output (SV, CO) and indexes (SI, CI) were determined by impedance cardiography. Mean arterial pressure (MAP) was directly related to PPB level, increasing by 23%, 32%, and 47% for each PPB level, respectively (p less than 0.01). HR, SV, and CO were unaffected after 4 min of 30, 50, and 70 mm Hg PPB. The results indicate that cardiovascular function decay is less severe than that reported using other PPB ensembles at similar PPB levels. Improved protection is most likely due to the greater pressurization of the G-suit and the 45% greater bladder volume in the leg bladders, leading to restored venous return and SV.
Adult↗
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↗
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↗
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↗
Inhibition of human gastric cyclic AMP production by Helicobacter pylori protein--possible involvement of mucosal prostaglandin E2.
The effect of Helicobacter pylori protein on cAMP and prostaglandin (PGE2) production was studied in incubates of human gastric fundic mucosa. At 24 hours, specimens incubated in the control fluid had a median cAMP value of 81 pmol/mg protein, compared to 28 pmol/mg (P less than 0.05) when incubated in H. pylori protein, 155 pmol/kg (P less than 0.006) in histamine, and 23 pmol/kg (P less than 0.05) in histamine plus H. pylori protein. A similar trend was observed at 48 hours. Although H. pylori protein had no direct effect on mucosal PGE2, it intensified the inhibitory effect of indomethacin and prevented the stimulatory effect of histamine on both PGE2 and cAMP production. Given the role of cAMP in various physiological responses, these results suggest that H. pylori protein might alter those functional aspects of the human gastric mucosa which rely on cAMP as a second messenger. Assuming that PGE2 is involved in mediating such effect, its role would appear to be either partial or indirect.
Bacterial Proteins↗
A randomized controlled trial of early amniotomy.
OBJECTIVE-To determine if a policy of early amniotomy resulted in a reduction in mean labour duration when compared to a policy of conservation of the membranes. DESIGN-A single-centre randomized controlled trial. SETTING-A tertiary care teaching hospital in Alberta, Canada. SUBJECTS-Ninety-seven term nulliparae in spontaneous labour, baby in cephalic presentation. INTERVENTION-Early amniotomy versus intent to keep membranes intact. MAIN OUTCOME MEASURES-Interval from randomization to delivery, rate of abnormalities of fetal heart rate tracings, cord artery blood pH, Apgar scores. RESULTS-The mean interval from randomization to delivery was 390.9 (SE 29.1) min in the amniotomy group and 442.9 (SE 34.1) min in the control group (P = 0.251). There were no differences between groups in the occurrence of fetal heart rate tracing abnormalities, nor was there a difference in the proportion of babies with abnormal Apgar scores, or abnormal cord pH (less than 7.20). CONCLUSION-The results of the study fail to support the long held belief that early amniotomy is an effective method for reducing labour duration.
Amnion↗
Parathyroid hormone-related protein of malignancy: immunohistochemical and biochemical studies in normocalcaemic and hypercalcaemic patients with cancer.
Immunohistochemical staining for parathyroid hormone-related protein was performed in 27 tumours from 19 normocalcaemic and eight hypercalcaemic patients with cancer. All the tumours from hypercalcaemic patients stained positively for the protein, as did 17 tumours from normocalcaemic patients. Only hypercalcaemic patients had biochemical evidence of increased bone resorption and abnormalities of renal tubular reabsorption of calcium and phosphate, consistent with the presence of parathyroid hormone-related protein. While tumour mass was higher in hypercalcaemic patients, only one of the initially normocalcaemic patients with positively staining tumours subsequently went on to develop hypercalcaemia and more advanced disease. These data confirm the importance of parathyroid hormone-related protein as a mediator of humoral hypercalcaemia in patients with solid tumours and suggest that low tumour mass may be one reason why serum calcium values are not increased in all patients with tumours containing parathyroid hormone-related protein. None the less normocalcaemia, despite tumour progression in patients whose tumours stained positively for parathyroid hormone-related protein, suggests that other factors may also be important, such as differences in the rate of secretion of the protein by different tumours, or the production of different forms of parathyroid hormone-related protein with varying biological effects.
Humans↗
Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease.
In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).
Adolescent↗
Use of bisphosphonates in hypercalcaemia due to malignancy.
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Clodronic Acid↗
Intact parathyroid hormone assays.
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Circadian Rhythm↗
The effects of intraoperative hypothermia and cardiopulmonary bypass on trace metals and their protein binding ratios.
The ability of intraoperative hypothermia to modify the metabolic response to cardiopulmonary bypass (CPB) was assessed by serial alterations in iron, zinc and copper, and in their molar binding ratios to their respective transport proteins, in 20 male patients under-going elective coronary artery surgery and randomised to an operative blood temperature of 28 degrees C or 20 degrees C. Decreases in serum iron and zinc concentrations, typical of the acute phase response, were preceded by early rises. Significant alterations in the metal: protein molar binding ratios preceded significant changes in the serum concentrations of the metals and occurred earliest in the zinc: albumin binding ratio, which was apparent by the time of skin incision. An intraoperative temperature of 20 degrees C modified iron and zinc concentrations and their protein binding ratios during surgery but not in the post-operative period. These early changes in trace metals and their protein binding ratios are a simple and inexpensive method of quantitating the response to surgical injury and may be useful in assessing new interventions in cardiopulmonary bypass. An awareness of the trace element response to surgical injury is essential to avoid misdiagnoses of iron deficiency anaemia or zinc deficiency.
Adult↗