Cystatin C levels in sera of patients with acute infectious diseases with high C-reactive protein levels.
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Acute Disease↗
Biomedical subjects
C Hasling
Publications and source records attributed to C Hasling.
Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function.
BACKGROUND: Cystatin C is a proteinase inhibitor with a low molecular weight. The serum levels of cystatin C are mainly dependent on glomerular filtration rate (GFR) making cystatin C an endogenous parameter of GFR. The aim of the study was to elucidate the applicability of serum cystatin C as a parameter of GFR in patients with normal to moderately impaired kidney function and to estimate a reference interval for serum cystatin C. PATIENTS AND METHODS: Forty-six patients (25 males and 21 females) aged 22 to 83 years with various kidney diseases and 250 blood donors (164 males and 86 females) aged 19 to 64 years were included. Cystatin C was measured by an automated particle-enhanced nephelometric immunoassay, serum creatinine by an enzymatic and by Jaffé method, urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA clearance. RESULTS: Serum levels ofcystatin C and creatinine showed increments with decreasing values of 99mTc-DTPA clearance and a linear relationship was found between 99mTc-DTPA clearance and l/serum cystatin C, l/serum creatinine (enzymatic method), and creatinine clearance. Comparison of the non-parametric receiver-operating characteristic (ROC) plots for serum cystatin C (area under the curve (AUC) = 0.996; SE = 0.005), serum creatinine (enzymatic method) (AUC = 0.899; SE = 0.044), serum creatinine (Jaffé method) (AUC = 0.870; SE = 0.051), measured creatinine clearance (AUC = 0.959; SE = 0.025), and estimated creatinine clearance (0.950; SE = 0.029) revealed significant differences for serum cystatin C and serum creatinine (enzymatic and Jaffé method) (p values: 0.03 and 0.01). No significant differences were demonstrated between serum cystatin C and measured and estimated creatinine clearance (p value: 0.14 and 0.12). The non-parametric reference interval for serum cystatin C was calculated to be 0.51-1.02 mg/l (median: 0.79 mg/l; range: 0.33 - 1.07 mg/l). CONCLUSION: Serum cystatin C seems to be a better parameter of GFR than serum creatinine in adults with various types of kidney disease with normal to moderately impaired kidney function.
Adult↗
Metabolic acidosis: an emerging problem in patients with intestinal segments as part of urinary diversion. A report of two cases.
Two cases of severe metabolic acidosis are reported, one of which led to severe disablement of the patient due to osteomalacia. Both patients had a urinary diversion performed years beforehand, one consisting of a continent ileal Kock reservoir and the other of a urethral Kock pouch. The mechanisms of these complications and their treatment are discussed.
Acidosis↗
A comparison of the effects of oestrogen/progestogen, high-dose oral calcium, intermittent cyclic etidronate and an ADFR regime on calcium kinetics and bone mass in postmenopausal women with spinal osteoporosis.
The effects of four different treatments for osteoporosis were compared in a prospective, randomized, 3-year study in 74 postmenopausal women with spinal crush fracture osteoporosis. Patients were randomly assigned to cyclic oestrogen/progestogen therapy (group 1, n = 20), a daily oral calcium dose of 2 g (group 2, n = 17), intermittent cyclic etidronate therapy (group 3, n = 19), or an ADFR treatment with triiodothyronine as activator and etidronate as depressor (group 4, n = 18). Spine and forearm bone mineral content was measured before entry and every 30 weeks. Combined calcium balance and 47Ca kinetic studies were performed before and after 1 and 3 years of treatment. Bone turnover, estimated by serum alkaline phosphatase and renal hydroxyproline excretion, decreased in all four groups during the first half of the treatment period but remained reduced during the second half in groups 1 and 3 only. Group 1 had a significantly positive calcium balance after 60 weeks of treatment. After 150 weeks, the positive effect on calcium balance was significant and greater in groups 1 and 3 than in the other groups. This was achieved by a greater reduction in resorption rate in group 1 at week 60 and in groups 1 and 3 at week 150 as compared with the other groups. Only group 1 had a significant increase in spinal bone mass while a decrease in bone mass at the distal forearm was observed in the etidronate-treated group. We conclude that treatment of postmenopausal osteoporosis with oestrogen/progestogen for 3 years results in net spinal bone gain and a positive effect on calcium balance slightly better than that of intermittent etidronate. These effects were inferior in the groups receiving a large calcium supplementation or the ADFR group where no change in calcium balance or bone mass was found.
Administration, Oral↗
Spine deformity index in osteoporotic women: relations to forearm and vertebral bone mineral measurements and to iliac crest ash density.
Bone densitometric measurements are widely used for monitoring therapeutic regimens for osteoporosis. However, it is a matter of debate which measurement site is most appropriate for prediction of individual fracture risk. The aim of this cross-sectional study was to investigate the relationship between bone mineral measurements at various sites and spine deformity index (SDI) in osteoporotic women. The SDI was determined in 37 osteoporotic women aged 56-87 years (mean 70.9 years). Peripheral (single-photon absorptiometry of the distal forearm, and iliac crest ash content) and axial (dual-photon absorptiometry of the lumbar spine) bone mass measurements were obtained. SDI increased with age (r = 0.34, p < 0.05), whereas forearm BMC (r = -0.52, p < 0.002) and forearm BMD (r = -0.62, p < 0.0001) decreased. No significant age-related changes were observed in lumbar BMC or iliac crest ash content in these osteoporotic women. A highly significant correlation was found between SDI and lumbar BMC (r = -0.60, p < 0.01). A significant, but less pronounced correlation was found between SDI and forearm BMC (r = -0.37, p < 0.05), whereas no relation was revealed between SDI and forearm BMD or iliac crest ash content. In a multiple regression model, the relationship between lumbar BMC and SDI remained significant after adjusting for the influence of age, whereas the relationship to forearm BMC disappeared. Furthermore, a multiple regression analysis was performed in order to evaluate the ability of all four bone mass measurements and age to predict variations in SDI.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Assessment of bone formation by biochemical markers in metabolic bone disease: separation between osteoblastic activity at the cell and tissue level.
In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Calcium metabolism in postmenopausal osteoporotic women is determined by dietary calcium and coffee intake.
Eighty-five patients, age 48 to 77 y with postmenopausal crush fracture osteoporosis, were investigated using a 7-d combined calcium balance and 47Ca tracer-kinetic turnover method taking the dermal calcium loss into account. Individual dietary records were obtained based on a 4-d registration at home before hospital admission and on questioning by a dietitian. The following dietary constituents were estimated: energy content, protein, methionine, cysteine, calcium, phosphate, magnesium, coffee, fiber and vitamin C. All patients were served individual diets based on the dietary records during study. Dietary calcium was measured in duplicates of all the meals served. All urine and feces were collected and analyzed for calcium content. The 47Ca kinetic data were analyzed according to a modification of the expanding calcium pool model. The overall calcium balance correlated significantly to energy content (r = 0.31, P less than 0.005), protein (r = 0.22, P less than 0.05), calcium (r = 0.28, P less than 0.01), phosphate (r = 0.27, P less than 0.02) and coffee (r = -0.21, P less than 0.05). However, a multiple backward linear regression analysis disclosed that only calcium (rp = 0.38, P less than 0.0005) and coffee intake (rp = -0.25, P less than 0.05) significantly influenced calcium balance. The equation was: calcium balance (mmol/d) = 0.14 x (dietary calcium, mmol/d) - 0.0016 x (coffee intake, mL/d) - 3.62. A coffee intake in excess of 1000 mL could induce an extra calcium loss of 1.6 mmol calcium/d, whereas intakes of 1-2 cups of coffee per day would have little impact on calcium balance.
Aged↗
Effects of a combined estrogen-gestagen regimen on serum levels of the carboxy-terminal propeptide of human type I procollagen in osteoporosis.
Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen-gestagen regimen in vivo we monitored serum levels of the carboxy-terminal propeptide of human type I procollagen (S-PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S-AP) and serum bone gla protein (S-BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p less than 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S-PICP also fell from 117 to 68 micrograms/liter at week 60 and 70 micrograms/ml at week 150 (P less than 0.01). This is equal to a reduction to 32 +/- 10% pretreatment levels. The reduction in S-PICP was not significantly different from that of the other two markers of bone formation (S-AP and S-BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen-gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen-mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.
Aged↗
Skeletal size and bone mineral content in Turner's syndrome: relation to karyotype, estrogen treatment, physical fitness, and bone turnover.
Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21-45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45.X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome.
Adult↗
The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.
Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Dermal, intestinal, and renal obligatory losses of calcium: relation to skeletal calcium loss.
Calcium balance is the difference between dietary calcium intake on the one hand and dermal, fecal, and urinary losses on the other. Bone is lost throughout adult life by at least three different mechanisms. Whether all these processes are affected by dietary calcium is at present unknown. In case they are not, dietary calcium intake should balance an adjusted value estimated as obligatory skeletal calcium loss minus obligatory external (dermal + intestinal + urinary) calcium loss. Such a correction would reduce estimated calcium allowances. To solve this question it is important, however, to ascertain whether obligatory bone loss is affected by dietary intake of calcium, ie, Can a high dietary calcium or calcium supplementation influence bone metabolism and reduce bone loss at all ages?
Bone Development↗
Calcium metabolism in postmenopausal osteoporosis: the influence of dietary calcium and net absorbed calcium.
A group of 85 females aged 48-77 years with postmenopausal crush fracture osteoporosis were investigated using a 7 day combined calcium balance and calcium tracer kinetic turnover study to assess the influence of dietary calcium and net absorbed calcium on bone metabolism. During the study, patients were on their habitual diet, as determined by a prestudy registration. Dietary calcium was measured after double serving of all the meals. All urine and feces were collected and analyzed for calcium content. Bone mineralization rate and bone resorption rate were determined by applying the continuously expanding calcium pool model to the tracer kinetic data. Urine calcium excretion and net absorbed calcium were correlated (r = 0.64, p less than 0.0001) with the following equation: urinary excreted calcium (mmol/day) = 2.4 + 0.4 X net absorbed calcium (mmol/day). Dermal calcium loss was not correlated with net absorbed calcium or urinary calcium. The net amount of absorbed calcium necessary to balance urinary and dermal losses was calculated to be 4.2 mmol calcium per day. The daily calcium intake necessary for obtaining a net absorbed calcium in excess of the urinary and dermal calcium losses and thereby ensure skeletal integrity was estimated to be 34.2 mmol calcium per day compared to an average intake of 27.9 +/- 7.6 (mean +/- SD) mmol/day. Net absorbed calcium correlated negatively to bone resorption rate (r = -0.31, p less than 0.005) and positively to bone mineralization rate (r = 0.29, p less than 0.01) and to calcium balance (r = 0.66, p less than 0.0001). Dietary calcium intake and calcium balance correlated positively (r = 0.38, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.
Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
[Serum parathyroid hormone (1-84) assessed by immunoradiometric methods can differentiate malignant hypercalcemia and primary hyperparathyroidism].
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Adult↗
Etidronate disodium in the management of malignancy-related hypercalcemia.
To evaluate the efficacy of intravenous etidronate disodium (etidronate) in controlling hypercalcemia of malignancy, 20 patients with known malignant disease and hypercalcemia were randomly assigned on a two-to-one basis to receive etidronate, 7.5 mg/kg of body weight, or placebo for three to five days. All patients received 3,000 ml of saline and 40 mg of furosemide per day. Eighteen patients completed the study. Eleven of 12 patients (92 percent) in the etidronate group attained normocalcemia, compared with two of six (33 percent) in the placebo group (p = 0.05). The etidronate group showed a greater decrease in the serum calcium level than did the placebo group (p less than 0.02). Renal calcium excretion decreased significantly in the etidronate group but not in the placebo group. Intravenous etidronate in combination with rehydration and furosemide constitutes a safe and effective alternative in the treatment of hypercalcemia of malignancy.
Adult↗
Dual-photon absorptiometry of the proximal tibia.
Dual-photon absorptiometric bone-mineral assay, penetration tests, and axial compression tests of the proximal tibial epiphyses were carried out in 18 human cadaver knees. The reproducibility of bone mineral assay was within +/- 12% (95% tolerance limits). Linear regression analysis with bone-mineral content as the independent variable showed a good correlation to the ultimate force obtained from the compression tests on the medial (r = 0.81) and the lateral (r = 0.90) condyles. The correlation between bone mineral content and an average of three condylar penetration tests was somewhat weaker (medical condyle: r = 0.65, lateral condyle: r = 0.62). It is concluded that dual-photon absorptiometric bone-mineral assay may be a suitable noninvasive alternative to bone-strength measurement and thus suitable for monitoring the changes in tibial condylar bone during follow-up studies.
Humans↗
Exogenous triiodothyronine activates bone remodeling.
The effect of exogenous triiodothyronine (T3) as an activator of bone remodeling was investigated by measuring biochemical marker levels. Fourteen people received 100-160 micrograms of T3 for 1 week and were followed for a total of 10 weeks. Serum T3 increased markedly during the first week, whereas serum TSH and serum thyroxine (T4) decreased. Bone resorption was stimulated during the first week as evaluated from serum calcium and renal excretion of calcium, phosphate, and hydroxyproline. Serum osteocalcin showed an increase in the first week, probably caused by stimulation of existing osteoblasts. Serum alkaline phosphatase increased from week 6 to week 8, and serum osteocalcin increased at week 8 to a level higher than the initial level. The results indicate that T3 acts as an activator of bone remodeling and initiates bone resorption followed by bone formation. The observed timetable for the remodeling sequence is in accordance with that obtained by bone histomorphometry. Osteopenic states may be treated by synchronizing the skeletal remodeling processes and then selectively depressing bone resorption with calcitonin or diphosphonates (ADFR treatment). Synchronization may be achieved by short-term treatment with a drug that stimulates the formation rate of new remodeling cycles (an activator). The results from this study indicate that exogenous T3 may be used as an activator.
Adult↗
Bisphosphonate whole body retention test: relations to bone mineralization rate, renal function and bone mineral content in osteoporosis and metabolic bone disorders.
The bisphosphonate whole body retention test (WBR) has been used to estimate bone mineralization rate (bone turnover). Bisphosphonates given i.v. are taken up by bone or excreted in urine. The aim of the present investigation was to test the efficacy of WBR in estimating bone mineralization rate (m) and to evaluate the influence of renal function (Clcr) and bone mass (forearm bone mineral content; BMC) on WBR. The 24-h retention of 3.7 MBq 99mTc-HMBP (1-hydroxymethylene-1,1-bisphosphonate) (Osteoscan) given i.v. was measured by a medium sensitive whole body counter in thirty-one patients with hyperparathyroidism (n = 14), hyperthyroidism (n = 8) or hypothyroidism (n = 9) (group 1) and in seventy-six females with postmenopausal spinal crush fracture osteoporosis (group 2). In the same individuals m was calculated from a 7-day 47Ca-kinetic study using the expanding calcium pool model. Multiple regression analysis of WBR vs. m and Clcr in group 1 disclosed that WBR correlated positively to m [rp = 0.49, P less than 0.01 (rp = partial correlation coefficient)] and inversely to Clcr (rp = -0.44, P less than 0.02). Inclusion of BMC in the analysis did not reveal any significant partial correlation between WBR and BMC (rp = -0.33, 0.05 less than P less than 0.10). In group 2 WBR correlated inversely to Clcr (rp = -0.48, P less than 0.001) but showed no significant relation to m (rp = 0.10, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗