Search

Objective: The purpose was to determine whether changes in the phosphate balance have an influence on the distribution of bone-seeking radiopharmaceuticals., Material and Methods: The biodistribution of 99mTc-HDP in mice, intravenously administered under varying conditions, was assessed by removing different organs and estimating their activity in a scintillation counter. Some experiments were also performed with 99mTc-MDP and 99mTc-DPD., Results: After 1 h and 18 h on phosphate-enriched drinking water, the mice showed a strongly increased uptake in all organs/tissues representing background activity and a decrease in the bone uptake. This pattern changed with time. After 6-8 days of phosphate load, we saw a more favourable distribution with a reduction of the background and whole-body activity. Administration of hPTH 1-34 gave rise to an activity distribution similar to that after 6-8 days on phosphate-enriched water. Changing the phosphate balance had less obvious effects on the distribution of 99mTc-MDP and 99mTc-DPD., Conclusion: The activity distribution of bone-seeking radiopharmaceuticals in the mouse is affected by the phosphate balance. The mechanism behind this finding is unknown but it may be partially mediated by PTH. It is possible that changes in the phosphate balance, induced by pharmaceuticals or by dietary changes, may affect the image quality at bone scintigraphy.

Objective: We studied the effect of long-term heparin treatment on bone mass during pregnancy., Study Design: Thromboprophylaxis with heparin was given to 39 women during pregnancy for a mean of 28 weeks and for an average of 6 weeks post partum. Bone mineral density measured with single-photon absorptiometry of the distal and ultradistal parts of the forearm was determined at the time of the start of heparin treatment (mean, twelfth week of gestation), immediately post partum, and on average 7 weeks post partum. The mean dosage of heparin was 17,300 IU/day. A control group of 34 normal pregnant women was studied for comparison., Results: In women treated with heparin, there was almost a 5% reduction in trabecular bone during pregnancy (p < 0.01) and an insignificant recovery post partum. There were no significant changes in bone mass during pregnancy or in the puerperium in the control group., Conclusion: Long-term treatment with heparin during pregnancy is associated with bone loss, but indications of reversible changes are observed.

Calcium homeostasis was longitudinally followed in serum and urine throughout normal pregnancy and the puerperium in 23 healthy women. From the 14th week of gestation, samples were obtained every fourth week until the 38th week. Post partum samples were obtained on the fifth day and after eight weeks. In the serum the total calcium decreased continuously during pregnancy. The ionized calcium and phosphate levels remained unchanged and within the reference interval for non-pregnant women. The alkaline phosphatase level progressively increased and high levels were found at term. The magnesium and hematocrit values remained below, whereas the calcitonin level remained just above the reference interval throughout pregnancy. The parathyroid hormone was low initially and increased towards term but within the reference interval. The urine excretion of calcium was constantly high, close to the upper reference limit, and renal function was slightly improved. At the last sampling eight weeks after delivery, all values were within normal limits for non-pregnant women. Calcium homeostasis is considerably changed during pregnancy and non-pregnant reference limits are not often valid.

Hyperprolactinemia is associated with decreased bone mineral density, which may be caused by the hypogonadism and hypoestrogenicity noticed in patients with hyperprolactinemia. Since calcitonin inhibits the bone resorption, and insulin-like growth factor I (IGF-I) has important anabolic effects on the skeleton, lack of one or both peptides may contribute to the development of osteopenia. We therefore measured the plasma calcitonin and IGF-I levels in nine women with hyperprolactinemia caused by a prolactin-producing pituitary tumor. The calcium-stimulated C-cell reactivity was studied by measuring calcitonin in plasma during a calcium clamp before and after normalization of serum prolactin during treatment with bromocriptine. Basal CT levels were measurable but lower than in healthy controls. Basal IGF-I levels and calcium-stimulated plasma calcitonin were normal in the hyperprolactinemic state and similar to the calcitonin and IGF-I levels during bromocriptine treatment. The serum prolactin levels decreased (p < 0.001) and the serum estradiol levels increased (p < 0.001). The bone mineral density of the lumbar spine increased significantly during treatment. Thus, basal plasma CT levels are slightly reduced in hyperprolactinemic women. However, the reversible osteopenia in hyperprolactinemic women is less likely to be caused by inhibited IGF-I secretion or by deficient CT levels since the CT response to calcium is normal. In addition, bromocriptine treatment with normalization of prolactin levels is beneficial for the bone mineral content in this condition.

Objective: To investigate the effect of subcutaneous heparin treatment on calcium homeostasis in pregnancy., Design: A longitudinal case-control observational study., Setting: Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden., Subjects: 36 pregnant women with previously verified thromboembolic complications and 23 healthy pregnant control women similar in age, parity, weight, and smoking habit., Interventions: Thromboprophylaxis during pregnancy and 6 weeks post partum was given with subcutaneous heparin twice daily to the 36 women with a history of thromboembolic complications, 16 received an average dose of 24,500 IU/day and 20 a mean dose of 17,300 IU/day. Venous blood and urine samples were obtained every 4 weeks., Main Outcome Measures: Serum concentrations of total calcium, ionized calcium, calcitonin and urinary calcium., Results: Women on high-dose heparin treatment showed significantly higher concentrations of total and ionized calcium and of calcitonin in serum and significantly lower concentrations of calcium in urine than did 23 normal pregnant controls. The differences were most pronounced in the third trimester. The results obtained in the low-dose heparin group were between those in the high-dose and the control groups. At 8 weeks postpartum there were no significant differences between the heparin-treated women and the controls. No significant differences were found during pregnancy in haematocrit, liver or renal function, serum levels of albumin, phosphate, magnesium, alkaline phosphatase, parathyroid hormone or urinary cyclic AMP., Conclusions: Heparin treatment during pregnancy results in changes in calcium homeostasis and a dose-dependent response is suggested.

Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day-1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.

The bone mineral content of the radius and ulna was analyzed in 31 postmenopausal women with displaced Colles' fractures. Sixteen fractures were treated with a below-the-elbow plaster case and 15 with primary external fixation. The bone mineral content of the forearm bones was measured with a photon absorptiometer 9 (6-24) months later. There was a mean 15 percent mineral decrease in the radius, but no difference between the two treatment groups. The decrease did not correlate with the age of the patient, nor was there any correlation with grip strength or range of wrist motion. The more severe fractures, according to the Frykman classification, had a more pronounced mineral loss than the simpler fractures.

The hypocalcemic and hypophosphatemic effect of salmon calcitonin (sCT) given by intranasal (i.n.) spray to 12 patients with histological confirmed primary hyperparathyroidism (1 degree HPT) was studied. The concentration of ionized calcium in whole blood (B-Ca++), serum phosphate (S-P), magnesium (S-Mg), plasma sCT (Pl-sCT), and endogenous CT (hCT) was followed during five 24-hour periods with at least three days between. After period I (control day), 100 IU sCT was given intramuscularly (i.m.) in period II. In periods III-V, either 110, 200, or 400 IU of sCT were given intranasally (i.n.) in randomized order. Although B-Ca++ decreased from the baseline value with all four sCT treatments and at 4.5 hour on the control day (p less than 0.05-0.001), the i.n. sCT treatments had no significant hypocalcemic effect, as the change of the area under the B-Ca++ curve (delta AUC B-Ca++) for the three i.n. treatments was not significantly different from the control period (p less than 0.001, ANOVA). Only the i.m. injection of calcitonin had a calcium-lowering effect (p less than 0.001, ANOVA). Three subjects were considered nonresponders with a decrease in B-Ca++ less than 0.06 mmol/L. S-P decreased within three hours after 200 IU sCT i.n. and 100 IU i.m., but the S-Mg levels showed no consistent changes. The area under the curve for the Pl-sCT levels did not correlate with delta AUC B-Ca++ except for i.m. given sCT.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentration of ionized calcium [Ca++] was reproducibly determined in human seminal plasma with a calcium sensitive electrode (Orion Space Stat 20). Dilution of the seminal plasma gave a linear decrease in free calcium concentration. Freezing and thawning or storage of the seminal plasma under anaerobic conditions did not influence the level of ionized calcium. Storage under aerobic conditions gave a temperature dependent decrease in CA++ which parallelled a spontaneous increase in pH. The mean concentration of ionized calcium (measured after a standardized air exposition) was 0.17 mM +/- 0.05 (SD) (range 0.09-0.29 mM). The Ca++ level was not correlated to the total calcium concentration or to markers for prostatic (zinc) or seminal vesicular (fructose) secretions. There were, however, more motile spermatozoa in semen samples with an ionized calcium level less than the average (0.17 mM) than in semen samples with a higher Ca++ level (53.8% +/- 8.4, N = 17 vs 45.0% +/- 12.8, N = 15, respectively, p less than 0.05). The percentage live spermatozoa was also higher (62.4% +/- 10.4, N = 17 vs 50.7% +/- 14.2, N = 15, p less than 0.01) in the semen samples with a low [Ca++]. Spermatozoa in the low [Ca++] group did also exhibit a better progressive motility than spermatozoa in the high [Ca++] group (p less than 0.05). It is suggested that the low level of ionized calcium in seminal plasma is of importance for motility of human spermatozoa and that the transfere of spermatozoa from a high Ca++ in the epididymis to the low levels in accessory sex glands secretion might be of significans for activation of spermatozoa upon ejaculation.

The concentration of immunoreactive calcitonin (iCT) in human milk was 10-40 times the serum level. Thus in milk samples collected from 29 mothers within one week and from 46 mothers three months post partum the levels of iCT were respectively 2.46 +/- 0.99 ng/ml (mean +/- SD) and 0.58 +/- 0.08 ng/ml. Eight of the 29 mothers delivered milk at two occasions, 1-2 and 4-6 days after delivery. There was a significant decline of iCT with about 20% during this period. One mother delivered milk for two months. During the first week after delivery the iCT decreased from 1.4 to 0.5 ng/ml and after that the iCT content remained rather constant. The level of ionized calcium (Ca++) was correlated to iCT the first week post partum (r = 0.72 p less than 0.01) but not in milk samples obtained after three months. The concentration of magnesium was weakly correlated to iCT during the first week post partum (r = 0.37 p less than 0.05). There was no correlation between iCT and the total calcium level nor to the concentration of zinc. The high concentration of iCT in milk compared to serum suggests a local production of iCT within the mammary gland or a specific transport and concentration mechanism.

The influence of sex steroid hormones on plasma calcitonin levels in healthy subjects was studied in 15 males and 10 premenopausal (PREMF) and 12 postmenopausal females (PMF). A standardized ionized calcium stimulus was achieved by means of the calcium clamp technique, and a sensitive RIA was used to determine immunoreactive CT (iCT) in plasma. Plasma iCT levels increased in response to the calcium clamp with an initial peak at 15 or 30 min. The iCT levels then declined but remained at an elevated level for the rest of the 180-min infusion period in all three groups. In males a positive correlation was found between the serum testosterone levels at 0 min and the estimates for initial iCT response, i.e., the change between 0 and 15 min (r = 0.80, n = 11, p less than 0.01), between 0 and 30 min (r = 0.56, n = 15, p less than 0.05) and between 0 and the maximum value (r = 0.68, n = 15, p less than 0.01). In the two female groups no such correlation was found. Serum 17 beta-estradiol or dehydroepiandrosterone sulfate concentrations were not correlated either to basal iCT levels or to the iCT response to the calcium clamp. PMF had lower levels of 17 beta-estradiol than PREMF (p less than 0.001), while the testosterone levels were similar. The iCT levels and response to the calcium clamp showed no significant difference in the two groups. The results indicate that sex difference in the plasma CT levels may be related to different testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypophosphataemia in connection with surgical trauma is most commonly ascribed to parenteral nutrition, glucose infusion, or haemodilution. We have earlier shown that patients with severe burns develop hypophosphataemia irrespective of such causes, and have introduced the theory that hypophosphataemia can result from the humoral response to trauma. In the present work, 10 otherwise healthy patients undergoing elective surgical treatment of old knee-ligament injuries were examined pre-, per-, and postoperatively with regard to phosphate, calcium, and magnesium homeostasis and hormones regulating this (parathyroid hormone, calcitonin, catecholamines). During operation we noted a significant and rapid fall in serum phosphate concentration, accompanied by increased secretion of calcitonin and catecholamines and a significant fall in serum magnesium. Unchanged fractional and total urinary phosphate excretion indicated that the fall in serum phosphate concentration was mainly due to prerenal causes.

The bone mineral content across the calcaneus was measured by gamma absorptiometry in 82 patients with operated on ankle fractures. A mean deviation in bone mineral content between the injured and the uninjured leg of 6 percent was found. Early weight bearing in a walking cast or brace did not influence the process of postfractural osteopenia. Compared with the patients with isolated lateral malleolar fractures, the patients with bimalleolar and trimalleolar fractures were older and had a lower bone mineral content in the calcaneus of their uninjured leg. The percentage of deviation in bone mineral content between the injured and uninjured leg was also greater in patients with more severe fractures.

Thirty-nine patients with disseminated carcinoma but without metastases to the adrenal glands underwent a complete physical examination and laboratory work-up regarding signs and symptoms suggestive of adrenal insufficiency. Thereafter, they were categorized into two groups. In group A, 24 patients were in relatively good condition and had no symptoms suggestive of adrenal insufficiency. All 15 patients in group B had clinical signs and symptoms similar to those usually associated with adrenal insufficiency. The adrenal activity of each patient was evaluated through determination of cortisol in plasma at 8 am, 2 pm and 8 pm; dexamethasone suppression-adrenocorticotropic hormone stimulating test; analysis of 24 hour urinary excretion of cortisol, and analyses of 24 hour urinary excretion of epinephrine and norepinephrine. After completion of the evaluation of adrenal function, the patients included in group B were treated with cortisone acetate. Patients in group B, when compared with those of group A, generally had an increase in cortisol secretion as well as in epinephrine and norepinephrine excretion. Both groups responded to dexamethasone suppression and adrenocorticotropic hormone stimulation. Of the 13 patients treated with cortisone, only one patient objectively responded to the treatment, while two of the patients were clinically improved. All three of these patients had normal or increased adrenal activity. It was concluded that the symptoms frequently seen in patients with disseminated carcinoma and which are similar to those associated with adrenal insufficiency, do not indicate impaired cortisol secretion. Patients with these symptoms usually had an increase in adrenal activity, probably as a response to stress.

A retrospective study was made of 17 severely burned patients with special reference to serum and urinary phosphate. A lowering of the serum phosphate level was regularly recorded between the 3rd and 9th day. The lowest mean value of serum phosphate of the group was 0.57 +/- 0.2 (S.D.) mmol/l (normal range 0.8-1.5 mmol/l) occurring on the 5th day after the accident. Serum phosphate then returned to normal levels in all the patients except three, who died. These three were among the four patients who showed the lowest serum phosphate values, less than 0.32 mmol/l, and their deaths coincided with the recording of these low values. The phosphate depletion seemed to be of prerenal origin. Hypophosphataemia may be of significance in the fatal outcome in some of the patients with severe burns.