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Biomedical subjects

O Tørring

Publications and source records attributed to O Tørring.

35 records · Page 2Linked to original sources

Salmon calcitonin treatment by nasal spray in primary hyperparathyroidism.

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)

Administration, Intranasal↗

Parathyroid hormone and parathyroid hormone-related peptide stimulate insulin-like growth factor-binding protein secretion by rat osteoblast-like cells through a adenosine 3',5'-monophosphate-dependent mechanism.

Specific insulin-like growth factor-binding proteins (IGFBPs) that may enhance or inhibit insulin-like growth factor (IGF) action are produced in various tissues. In the present study we demonstrated that IGFBPs are synthesized and secreted by rat osteoblast-like cells (UMR 106-01). PTH and PTH-related peptide (PTHrP) were potent stimuli for IGFBP production by UMR cells, whereas GH, IGF-I, insulin, epidermal growth factor, and T3 had little or no effect. A maximal 8- to 30-fold increase in IGFBP production was attained at 10(-7)-10(-6) M PTH and PTHrP, with a half-maximal effect at approximately 10(-9) M. By Western blot analysis, PTH and PTHrP markedly and selectively increased the production of 29,000 mol wt (Mr) and, to a lesser extent, 24,000 Mr IGFBPs. Agents that elevate intracellular cAMP by different mechanisms [(Bu)2cAMP, forskolin, and isobutylmethylxanthine] mimicked the effect of PTH and PTHrP on IGFBP synthesis. In comparison, PTH did not stimulate IGFBP production in fibroblasts and ROS 17/2.8 cells, which secrete IGFBPs of 42,000, 38,000, 34,000, 28,000, and 24,000 Mr, but not of 29,000 Mr. The PTH-responsive IGFBPs from UMR cells were nonglycosylated proteins with preferential affinity for IGF-I over IGF-II. These IGFBPs were not immunoprecipitated with antisera against rat IGFBP-2 or human IGFBP-1. Thus, PTH and PTHrP increase the production in UMR 106-01 cells of discrete IGFBP forms with Mr of 29,000 and 24,000 through a cAMP-mediated mechanism, independent of IGF-I synthesis. Taken with the known effects of PTH on IGF production in bone cells, the data suggest that PTH and PTHrP may modulate local IGF action in bone through the regulation of specific IGFBP availability.

Animals↗

The anabolic effects of human parathyroid hormone (hPTH) on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing: a comparison study between hPTH-(1-34) and hPTH-(1-84).

PTH has a proven anabolic effect on bone mass, as has been shown in several animal models and treatment regimens. The aim of this study was to ascertain whether the positive effect on bone mass is also reflected in the quality of bone formed. The study was performed in a rat model using human PTH (hPTH). One hundred and twenty male Wistar rats, divided into 10 groups, were given either hPTH-(1-34) or hPTH-(1-84) in daily sc doses. Dose levels ranged from 0.11-3.00 nmol/100 g BW.day for a period of 30 days. At death all six lumbar vertebrae were obtained from each rat. A combination of methods was applied to these vertebral bodies in order to ascertain the effect of hPTH on vertebral bone volume, density, trabecular structure, and biomechanical competence. The results revealed a dose-dependent increase in total volume, dry weight, ash weight, and trabecular bone volume. Also, a dose-dependent increase in load values could be demonstrated. The increase in bone strength remained significant after normalization for both cross-sectional area and bone mass. This indicates that the increase in bone size and bone mass was not achieved at the expense of the quality of the bone present. When the two treatments were administered at the same molar dose level, no difference between hPTH-(1-34) and hPTH-(1-84) was revealed. On the basis of this study, it is concluded that PTH could prove to be a promising treatment in the management of osteopenic states.

Animals↗

["Emergency: is there a doctor on board the flight?" Of course we can help you!].

Many Scandinavian physicians are hesitant to render emergency care on board an international flight due to the fear of a malpractice lawsuit, especially in the US. However, the risk for a lawsuit under these circumstances a negligible provided the doctor, called for by the cabin crew, does not act in a willfull and wanton or reckless manner. Good Samaritan laws in all states of USA provide a doctor or other person who renders emergency care outside a medical center with general immunity from liability.

Aircraft↗

Postmenopausal osteoporosis: response of immunoextracted calcitonin to a calcium clamp.

Fourteen postmenopausal females with osteoporosis (PMO) and 14 healthy postmenopausal females (PMF) were studied by means of the calcium clamp-technique. Plasma was collected before start and during the 1 hour calcium clamp. Calcitonin (CT) was immunoextracted from plasma with antiserum No. 1 directed against the mid- and carboxyterminal portion of CT. Thereafter radioimmunoassay was performed on the extracts with antiserum No. 2 directed against the carboxyterminal of CT. The detection limit of the assay was 0.8 pg/tube. There was no difference between patients and controls in the basal CT values and CT was detectable in all samples after immunoextraction. Plasma CT increased significantly during the calcium clamp in osteoporotic patients as well as in controls and the CT response did not differ between the groups. The results do not support the hypothesis of a diminished CT secretion as a contributing factor to the development of osteoporosis.

Aged↗

The influence of sex steroid hormones on plasma calcitonin response to the calcium clamp in normal subjects.

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)

Adult↗

Saliva and sweat secretion in man during a one-hour calcium clamp.

The effect of a 1-h calcium infusion, directly regulated to obtain and maintain a predetermined blood calcium level ('calcium clamp'), on the composition of parotid saliva, mixed saliva, and sweat was determined in healthy volunteers. An increase in amylase content of the parotid saliva under hypercalcaemic conditions was observed, but the 'calcium clamp' had no effect on flow rate, total and ionized calcium, sodium, potassium, and phosphate levels as well as pH in parotid and mixed saliva. The sweat calcium concentration was negatively correlated with sweat rate, in contrast to sodium and chloride concentrations. Increasing serum calcium levels did not affect ionic composition of the sweat and sweat flow rate.

Adult↗

Plasma calcitonin response to a calcium clamp in endogenous Cushing's syndrome.

Basal and calcium (Ca) stimulated plasma CT concentrations have been studied in 6 premenopausal females with Cushing's disease and 3 premenopausal females with Cushing's syndrome due to an adrenocortical adenoma. Thirteen healthy premenopausal females served as a reference group. A standardized Ca-stimulus was applied to all subjects by means of the 'calcium clamp' technique. Plasma immunoreactive CT (iCT) was determined by RIA using a carboxyl terminal antiserum with 8 pg-eq/ml as detection limit. The patients with Cushing's disease had normal basal plasma iCT levels and their iCT response during the 2 h calcium clamp was within the reference range in 5 out of 6 patients, the remaining patient showed a slightly exaggerated response. The patients with adrenal adenoma had elevated plasma iCT levels in the basal state but a normal response during the calcium clamp. It is therefore less likely that the bone resorption often seen in Cushing's syndrome is due to CT deficiency.

Adenoma↗

Plasma calcitonin response to a calcium clamp. Influence of sex and age.

The influence of sex and age on basal and calcium stimulated immunoreactive plasma calcitonin (iCT) were studied in 36 healthy subjects. An identical calcium stimulus, "calcium clamp", was applied to 10 young males, 13 premenopausal females of similar ages and 13 postmenopausal females. A significantly greater iCT response was found in males compared with both female groups. No age correlation in basal or calcium stimulated iCT levels was observed despite 35 years difference in mean age between the pre- and postmenopausal groups. A positive correlation between the induced change in whole blood ionized calcium (B-Ca++) and the iCT response, recorded after 15 min, was seen in young subjects of both sexes. Basal iCT and B-Ca++ were similar in all three groups. No correlation between basal iCT and basal B-Ca++, or between basal iCT and age was found. The total amounts of infused calcium per kg body weight were equal. The results indicate that male subjects have a greater secretory capacity of the thyroid C-cell than females. No reduction of the secretory capacity was observed with increasing age in females, neither was any difference found between pre- and postmenopausal females of the iCT-response.

Adult↗

Effects of a three-hour calcium clamp on calcium, phosphate, magnesium and zinc concentrations of human parotid saliva.

Ionized (saliva-Ca2+) and total calcium (saliva-CaT), inorganic phosphate (saliva-P), magnesium (saliva-Mg), and zinc (saliva-Zn) levels in parotid saliva were studied in eight healthy volunteers during a 3-h calcium infusion, directly regulated to obtain a pre-settled standardized blood calcium level. Frequent determinations of whole blood ionized calcium (B-Ca2+) were used for continuous adjustments of the calcium infusion rate ('calcium clamp'). Basal B-Ca2+ (1.26 +/- 0.04 mmol X l-1, mean +/- SD) was thus elevated to and maintained at 1.51 +/- 0.05 mmol X l-1 from +30 to +180 min. Saliva samples were taken prior to the infusion and at regular intervals during the infusion period. Saliva-Ca2+ decreased from 0.38 +/- 0.06 to 0.33 +/- 0.05 mmol X l-1 (P less than 0.01) and saliva-Ca2+ as a percentage of saliva CaT from 63 +/- 7% to 53 +/- 10% (P less than 0.001) during the infusion. No changes could be observed in saliva-CaT, saliva-P, saliva-Mg, saliva-Zn, saliva-Na and saliva-K. Possible mechanisms behind these findings might be decreased parathyroid hormone and increased calcitonin concentrations in serum.

Adult↗

Decreased plasma calcitonin response to a calcium clamp in primary hyperparathyroidism.

In order preoperatively to evaluate the calcium induced plasma calcitonin (CT) response in patients with mild primary hyperparathyroidism (PHPT), 7 postmenopausal (PM) females with PHPT and 14 PM healthy subjects underwent a 2 h calcium infusion. The infusions were performed by means of the 'calcium clamp' technique previously described by us in order to obtain an identical calcium stimulus in all subjects. Immunoreactive calcitonin (iCT) was determined by means of a sensitive RIA utilizing rabbit antibodies directed against the carboxy-terminal amino acid sequence of the CT molecule. All patients with PHPT had normal basal plasma iCT levels: 10 +/- 5 pg-eq/ml (mean +/- SD) as a group and not different from the control group: 13 +/- 5 pg-eq/ml. In the control group significantly increased plasma iCT was seen at 30, 60, 90 and 120 min in contrast to that of the PHPT group where a blunted response was observed. The results indicate a diminished CT reserve in these patients which may imply an impaired defence against the PTH mediated bone resorption seen in patients with PHPT.

Adenoma↗

Gel chromatography of immunoextracted plasma calcitonin in response to the calcium clamp in healthy males.

A radioimmunoassay (RIA) was developed for immunoreactive calcitonin (iCT) in human plasma. Antibodies against synthetic human calcitonin (hCT) coupled to bovine serum albumin (BSA) were raised in rabbits and were directed against the carboxy terminal part of CT. The detection limit of the assay was 8 pg/ml. In 7 males the iCT response to a calcium-clamp was studied. Blood was collected at 0, 30 and 60 min after the start of the calcium infusion. iCT was measured directly in plasma and in extracts obtained after purification of plasma iCT by means of immobilized CT antibodies. There was a good correlation between iCT in plasma samples and extracts, r = 0.993, n = 14 (P less than 0.001). Dilution curves of extracts and plasma were parallel with the hCT standard curves. Gel chromatography of the extracts on Sephadex G-50 and G-75 disclosed heterogeneity of iCT in normal plasma during basal conditions as well as during calcium stimulation. Thirty min after the start of the calcium clamp all molecular forms, most likely constituting monomeric and dimeric CT and larger forms, were increased, while after 60 min iCT seemed to constitute predominantly forms larger than monomeric CT. Basal levels of unextracted iCT in healthy males (n = 44, 37 +/- 10 years) were 15 +/- 9 pg-equivalents/ml (mean +/- SD) which was higher than in females (n = 40, 32 +/- 9 years) 11 +/- 4 pg-equivalents/ml (P less than 0.05).

Adult↗

A calcium clamp technique in man.

Calcium infusion imply a risk for cardiovascular complications. To avoid the risk, we have developed a new method for calcium infusion in man which can keep ionized calcium concentration in whole blood (WB-Ca++) in a steady state at a predetermined level. A solution of calcium chloride (Calcii chlor. Nord.), containing 0.117 mmol Ca++/ml water, is infused intravenously by means of an IMED 922H infusion pump. WB-Ca++ is determined every 5-10 min with a calcium ion-selective electrode, NOVA 2. The infusion rate is continuously adjusted. With the same initial infusion rate, 0.31 mmol Ca++/kg b.w./hour, hypercalcemia that is WB-Ca++ above 1.27 mmol/l was reached within 10 min in healthy volunteers, 8 females with a mean age of 26 years (range 19-36) and 7 males with a mean age of 29 years (range 25-34). The presettled WB-Ca++ level, 1.45 mmol/l, was obtained within 25 min and maintained in a steady state for 155 min at 1.45 +/- 0.01 mmol/l (mean +/- SE) in the female and at 1.46 +/- 0.01 mmol/l in the males. The range of the individual steady state mean WB-Ca++ was 1.42 +/- 0.02 mmol/l. No side-effects of the infusion were noted except for a slight increase in systolic and diastolic blood pressure 60 min after start of the infusion. In conclusion, the calcium clamp technique is safe and suitable for such situations where a presettled easily controlled WB-Ca++ level is required.

Adult↗

An ionized calcium regulated calcium clamp technique in man.

A new method for calcium infusion in man is described. It is possible with this method to select, obtain and maintain a whole blood ionized calcium (WB-Ca++) level in a steady state by means of frequent ionized calcium determinations. Using the same initial calcium chloride infusion rate 17.55 mmol Ca++ per hour) in three groups of normocalcemic patients (n = 23), hypercalcemia (i.e. WB-Ca++ greater than 1.32 mmol/l) was reached within 7-15 minutes; the desired level of WB-Ca++ (1.45 mmol/l) was obtained within 15-35 minutes. This level could then be maintained throughout the infusion period, 120 minutes. Thus, postmenopausal females with osteoporosis (n = 10) showed steady state WB-Ca++ levels of 1.46 +/- 0.09 mmol/l (mean +/- s.d.), premenopausal females (n = 5) 1.45 +/- 0.05 mmol/l and males (n = 8) 1.43 +/- 0.05 mmol/l. The difference between the mean WB-Ca++ for the steady state period and the desired level was less than or equal to 0.04 mmol/l in each individual. With a coefficient of variation of less than or equal to 0.04 in each individual for WB-Ca++ during the steady state the physiologically active calcium fraction could be kept remarkably constant. No complications were noted during the infusion. The calcium clamp technique described is safe and suitable for purposes where a presettled, easily controlled WB-Ca++ level is needed in man.

Calcium↗

Urinary cyclic AMP corrected for glomerular filtration rate in the differential diagnosis of hypercalcemia.

To evaluate the usefulness of urinary cyclic AMP (U-cAMP) expressed as nmol/100 ml glomerulus filtrate (GF) when discriminating various hypercalcemic states, we studied 99 patients. Patients with primary hyperparathyroidism (PHPT) showed a positive correlation between individual S-calcium levels and U-cAMP, nmol/100 ml GF (females r=0.49, n=40, p less than 0.01 and males r=0.91, n=7 p less than 0.001). There was also a correlation between U-cAMP, nmol/100 ml GF, and the weight of the adenomas (females r=0.36, n=32, p less than 0.05) and males r=0.79, n=6, p less than 0.05). Patients with PHPT and normal renal function excreted more U-cAMP than controls, 6.0 +/- 1.6 versus 4.3 +/- 1.0 nmol/100 ml GF (mean +/- SD). Of 47 patients with PHPT and normal renal function, 29 showed values below the upper normal limit, 6.3 nmol/100 ml GF (mean +/-2 SD), of the control group; the overlap was 62%. When U-cAMP was expressed as mumol/24 hours, the overlap was 40/47 (85%) and, when expressed as mumol/g creatinine, 31/47 (66%). Three patients with sarcoidosis and two with malignancies and hypercalcemia showed excretory values of U-cAMP, nmol/100 ml GF, above the upper normal limit. Patients with acromegaly or prolactinoma showed normal values of U-cAMP, nmol/100 ml GF. The present data indicate that all three types of determinations of urinary cAMP based on 24 hour urine collections are of little value in the differential diagnosis of hypercalcemic states.

Acromegaly↗