Serum amino terminal type III procollagen peptide and serum hyaluronan in rheumatoid arthritis: relation to clinical and serological parameters of inflammation during 8 and 24 months'' treatment with levamisole, penicillamine, or azathioprine.

Increased serum levels of the amino terminal type III procollagen peptide and serum hyaluronan were demonstrated in patients with rheumatoid arthritis. In patients with active disease a significant correlation was shown between serum levels of the propeptide and hyaluronan and the clinical signs of synovitis reflecting the extent of synovial inflammation. During recovery the serum propeptide and serum hyaluronan showed a delayed decline as compared with the clinical signs of synovitis and the acute phase protein response. This probably reflects the presence of persistent subclinical chronic inflammation. Normal serum propeptide levels in rheumatoid arthritis were associated with a good prognosis without progression of erosive joint lesions. Azathioprine reduced the number of patients with progression of erosive joint lesions and caused a more marked suppression of the serum propeptide than levamisole and penicillamine.     

Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients.

The aim of the current study was to evaluate bone metabolism and mass before and after 2 years of GH replacement therapy in adults with childhood or adulthood onset GH deficiency. Thirty-six adults with GH deficiency, 18 with childhood onset, 18 with adulthood onset GH deficiency and 28 sex-, age-, height- and weight-matched healthy subjects entered the study. Biochemical indexes of bone turnover such as serum osteocalcin, serum carboxyterminal telopeptide of type-I procollagen, urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine, of soft tissue formation such as aminoterminal propeptide of type-III and bone mineral density were evaluated. Childhood onset GH deficient patients had significantly decreased bone (osteocalcin: 2.5+/-1.3 vs 6.6+/-4.8 mcg/l, p<0.001) and soft tissue formation (aminoterminal propeptide of type III: 273+/-49 vs 454+/-23 U/I, p<0.001) indexes and normal bone resorption indexes (serum carboxyterminal telopeptide of type-I procollagen: 105+/-48 vs 128+/-28 mcg/l p=NS; urinary hydroxyproline/creatinine: 0.19+/-0.16 vs 0.28+/-0.16 mmol/mol, p=NS; urinary deoxypyridinoline/creatinine: 21 +/-10 vs 25+/-8 mcmol/mol, p=NS) compared to healthy subjects. On the contrary, no significant difference in bone turnover indexes between adulthood onset GH deficient patients and healthy subjects was found. Moreover, significantly decreased bone mineral density at any skeletal site and at whole skeleton was found in GH deficient patients compared to healthy subjects (e.g. femoral neck: 0.74+/-0.13 vs 0.97+/-0.11 g/cm2, p<0.001). In addition, a significant reduction of bone mineral density was found in childhood compared to adulthood onset GH deficient patients at any skeletal site, except at femoral neck. After 3-6 months of treatment, both groups of patients had a significant increase in bone turnover and in soft tissue formation. In particular, in childhood onset GH deficient patients after 3 months osteocalcin increased from 2.5+/-1.3 to 7.9+/-2.1 mcg/l, p<0.001 aminoterminal propeptide of type-III from 273+/-49 to 359+/-15 U/I p<0.001; serum carboxyterminal telopeptide of type-I procollagen from 105+/-48 to 201+/-45 mcg/l, p<0.001; urinary hydroxyproline/creatinine from 0.19+/-0.16 to 0.81+/-0.17 mmol/mol, p<0.001; urinary deoxypyridinoline/creatinine from 21 +/-10 to 54+/-20 mcmol/mol, p<0.001; while in adulthood onset GH deficient patients after 6 months osteocalcin increased from 4.2+/-3.6 to 6.5+/-1.9 mcg/l, p<0.05; aminoterminal propeptide of type- III from 440+/-41 to 484+/-37 U/I, p<0.05; serum carboxyterminal telopeptide of type-I procollagen from 125+/-40 to 152+/-22 mcg/l, p<0.05; urinary hydroxyproline/creatinine from 0.24+/-0.12 to 0.54+/-0.06 mmol/mol, p<0.001; urinary deoxypyridinoline/creatinine from 23+/-8 to 42+/-5 mcmol/mol, p<0.001. No significant difference in bone turnover between pre- and post-treatment period was found after 18-24 months of GH therapy. Conversely, bone mineral density was slightly reduced after 3-6 months of GH therapy, while it was significantly increased after 18-24 months. In fact, femoral neck bone mineral density values significantly rose from 0.74+/-0.13 g/cm2 to 0.87+/-0.11 g/cm2 (pre-treatment vs 2 years of GH treatment values). In conclusion, patients with childhood or adulthood onset GH deficiency have osteopenia that can be improved by long-term treatment with GH.     

Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism

BACKGROUND In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an aminoacid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery. METHODS Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit. RESULTS Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (?55 and ?31% respectively). Twenty-five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH. CONCLUSION Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.     

Bone alkaline phosphatase isoenzyme and urinary hydroxyproline in healthy subjects, patients with osteolytic metastases, and patients with primary hyperparathyroidism

The values of urinary hydroxyproline excretion reflecting the bone remodelling by osteoclasts, and the bone isoenzyme of serum alkaline phosphatase reflecting the osteoblastic function, in 100 randomly selected healthy subjects, 100 patients with primary hyperparathyroidism, and 100 patients with osteolytic secondary tumorous deposits in the skeleton showed a bivariate lognormal distribution. Hotelling's test revealed highly significant differences in the biochemical values among these three conditions, even when Bonferroni's modification of the test was used. The individual biochemical values, however, displayed many mutual overlaps. Despite this, the discriminatory analysis based on bivariate biochemical data resulted in a correct diagnosis in all healthy subjects, in 82 patients with primary hyperparathyroidism, and in 93 patients with osteolytic metastases. The simultaneous determinations of urinary hydroxyproline excretion and the bone alkaline phosphatase insoenzyme improve the differential diagnosis between these conditions. The predominance of urinary hydroxyproline excretion relative to bone alkaline phosphatase isoenzyme suggests an osteolytic metastasis. Proportionately elevated both hydroxyproline and bone alkaline phosphatase isoenzyme indicate the presence of primary hyperparathyroidism. This shows the importance of a correct biometrical processing of data. Nevertheless, a complex clinical evaluation is always mandatory.     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse. Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.     

Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males*

OBJECTIVE In view of the fact that GH-deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH-deficient adult males. DESIGN We performed a 6-month randomized, double-blind, placebo-controlled study, followed by 12–24 months of GH treatment in all patients. PATIENTS Twenty adult males with GH deficiency of childhood onset were studied. MEASUREMENTS We measured serum IGF-I, serum phosphate, biochemical indices of bone turnover (serum alkaline phosphatase activity, serum osteocalcin, serum carboxyterminal propeptide of type-I procollagen, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios) and bone mineral content, measured at the forearm and the lumbar spine by single and dual-photon absorptiometry respectively. RESULTS After 3 and 6 months of GH administration, the serum levels of alkaline phosphatase, osteocalcin and carboxyterminal propeptide of type-I procollagen, and the fasting urinary hydroxyproline/creatinine ratio were significantly increased compared to placebo-treated patients (P<0.01 to P<0.001). During the open study phase, the values for these indices of bone turnover remained elevated above pretreatment levels (P<0 01 to P<0 001 at 12 months), a downward trend becoming apparent after about one year of GH treatment. BMC values showed an initial decline after 3 months of GH treatment (most likely due to an expansion of the remodelling space), followed by a significant and progressive increase above pretreatment values, reaching 7–8% for total BMC at the lumbar spine (L2-L4) and 9–9% for total BMC at the forearm, after 30 months of GH administration. CONCLUSIONS The data of our study show that administration of substitutive doses of growth hormone to GH-deficient adult males activates bone turnover for a period of at least one year and suggests that this may have a beneficial effect on bone mass in these patients.     

Increased serum concentrations of type I procollagen C-terminal propeptide and osteocalcin during a short course of calcitriol administration to adult male volunteers.

To investigate bone collagen metabolism during vitamin D treatment, 15 healthy males (aged 28-45 years, median 34) were treated orally with calcitriol, 2 micrograms daily for 7 days and followed for a total of 2 weeks. The serum concentration of calcitriol rose markedly (median difference and 95% confidence limits: 49% (5-82), p less than 0.005) during treatment, whereas serum levels of calcidiol, and calcium remained unchanged. The serum level of procollagen type I C-terminal propeptide rose 15% (7-33, p less than 0.003), whereas no alterations were observed concerning serum procollagen type III N-terminal propeptide, and serum hyaluronan. The serum concentration of osteocalcin rose concomitantly (26% (12-45), p less than 0.003). All values returned to baseline levels within seven days after the treatment week. The serum levels of osteocalcin and procollagen type I C-terminal propeptide were positively correlated (rs = 0.71, p less than 0.004) during the study. Serum procollagen type I C-terminal propeptide and serum osteocalcin did not correlate with serum procollagen type III N-terminal propeptide or serum hyaluronan either at baseline or after treatment. It is concluded that a short course of calcitriol administration to healthy males stimulates the biosynthesis of bone-related matrix proteins. By contrast, connective tissue components of predominantly extraosseous origin are not affected.     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.     

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity

Objective. To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. Methods. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. Results. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. Conclusion. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.     

Serum and synovial fluid hydroxyproline fractions in microcrystalline arthritis and osteoarthritis

Synovial fluid and serum hydroxyproline fractions were investigated in patients with osteoarthritis and microcrystalline arthritis. Synovial fluid dialysable hydroxyproline levels are higher than serum levels in both conditions. Synovial fluid total and dialysable hydroxyproline are higher in microcrystalline arthritis than in osteoarthritis, while non-dialysable hydroxyproline values are similar in both conditions. In microcrystalline arthritis, synovial fluid dialysable hydroxyproline and polymorphonuclear leukocyte counts closely parallel each other. Irrespective of the type of arthropathy, synovial fluid dialysable hydroxyproline levels correlate with urinary hydroxyproline excretion. While the data suggest overproduction of dialysable hydroxyproline by joints in both conditions, the overproduction appears to be mediated by polymorphonuclear leukocytes in microcrystalline arthritis only. The ratio of serum to synovial total hydroxyproline are further suggestive of a possible differentiation between osteoarthritis and microcrystalline arthritis. In the conditions governing the present study, urinary hydroxyproline may be used as an index of joint tissue collagen resorption. Finally the significance of synovial fluid and serum non-dialysable hydroxyproline is discussed.     

Hyaluronic acid and N-terminal procollagen-III-peptide in the urine in inflammatory and degenerative joint diseases

In a cross-sectional study of 130 patients (main diagnosis: rheumatoid arthritis, n = 41, osteoarthritis, n = 39; ankylosing spondylitis, n = 28) we measured the concentrations of hyaluronan (HA) and the N-terminal propeptide of type-III collagen (NP III P) in urine and evaluated the relationship with their serum levels. Increased HA levels in serum correlated with increased urinary excretion (r = 0.69 for patients with active rheumatoid arthritis). Only patients with rheumatoid arthritis showed significantly elevated HA concentrations in urine (mean = 1,493 micrograms/mmol creatinine). Because of relatively wide fluctuations in urinary HA in normals (mean = 944, standard deviation 818 micrograms/mmol creatinine) and only modest differences between groups, the diagnostic accuracy of urinary HA measurements is inferior to serum determinations. NP III P showed no significant differences between patients and controls (means 10.5 to 15 micrograms/mmol creatinine). Obviously, renal excretion is of minor importance in the metabolism of HA and NP III P. The possible diagnostic usefulness of determinations of these parameters in serum is not enhanced by measurements in urine.     

Hepatic and renal extraction of circulating type III procollagen amino-terminal propeptide and hyaluronan in pig

Hepatic and renal clearance of the amino-terminal propeptide of type III procollagen (PIIINP) and of the glycosaminoglycan, hyaluronan (HA) were investigated in a catheterization study of seven healthy anesthetized pigs. Two assays were used, in order to distinguish between the metabolism of different PIIINP-related antigens. One was the PIIINP RIA Kit, which measures the intact propeptide. The other was the PIIINP Fab assay, in which the antibody has an equal affinity to the intact propeptide and to smaller fragments, of which the latter constitutes most of the antigenic activity in serum. Hepatic and gastrointestinal extraction were evaluated from measurements of serum concentrations in the artery, the portal vein and the hepatic vein. We found a significant hepatic extraction of the intact propeptide (extraction ratio 0.14) and of HA (extraction ratio 0.23), but not of smaller PIIINP fragments. No gastrointestinal extraction of any of the tested substances could be demonstrated. Only smaller PIIINP fragments (such as the col 1 fragment) were extracted by the kidneys (the extraction ratio in the PIIINP Fab assay was 0.19). The renal extraction ratio of HA was 0.14. The amounts of PIIINP fragments and of HA extracted by the kidneys were 50- and 3-times the amounts found in urine, respectively, indicating that the col 1 fragment and HA are degraded in the kidneys in addition to urinary excretion. Our results suggest a dynamic turnover of connective tissue-related components with a fast catabolism of circulating components in liver and kidneys.     

Schistosoma mansoni infection in a recently exposed community in Senegal: lack of correlation between liver morphology in ultrasound and connective tissue metabolites in serum

Summary Four hundred and seventy villagers of Ndombo, a village with recently established intensive transmission of Schistosoma mansoni in the Senegal River Basin, were enrolled in a study with the intention to assess hepatosplenic morbidity. All patients were examined parasitologically and by ultrasound. Hepatic fibrosis serum markers were determined in 153 adult patients (aminoterminal propeptide of procollagen type III, hyaluronan and laminin). By ultrasound, about 60% of the patients showed early stages of hepatic involvement, 3% of the patients unequivocally showed severe hepatosplenic pathology (grade 3 according to the Managil classification), whereas in another study performed in the same village 3 years earlier, no patients with severe hepatosplenic pathology had been found. No correlation between the aminoterminal propeptide of procollagen type III, hyaluronan or laminin and the ultrasound findings could be established. These hepatic fibrosis serum markers do not seem to be a sensitive method to detect early hepatic fibrosis in schistosomiasis.     

Assessment of relationship between secretion of melatonin, activity of thyroid, adrenal cortex as well as testes and chosen markers of collagen metabolism in starved rats

In starved rats the mutual interrelations were studied between the secretion of melatonin (MEL), thyroid hormones (TT[_4], FT[_4], TT[_3], FT[_3], rT[_3]), corticosterone (B), testosterone (T) and some markers of collagen metabolism: serum concentrations of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) (determined by RIA method) as well as urine concentration of hydroxyproline (OH-Pr) (determined by colorimetric method). Starved rats were found to have significantly increased serum MEL, B, and rT[_3] concentrations while serum values of TT[_4], FT[_4], TT[_3], FT[_3], T and PICP as well as urinary OH-Pr were significantly decreased. The concentrations of PICP, PIIINP and OH-Pr correlated negatively with MEL and B values, but positively with TT[_4] and FT[_4]. It was concluded that starving may change the collagen metabolism in rats indirectly via a modulating effect of changes in MEL, thyroxine and corticosterone.     

Effect of fluoride therapy on nondialyzable urinary hydroxyproline,serum alkaline phosphatase,parathyroid hormone,and 25-hydroxyvitamin D

The effect of sodium fluoride therapy was studied in 40 osteoporotic male subjects, aged 50–80 yr. Twenty patients were treated with sodium fluoride (20–40 mg/day) and 20 received placebo for 107 wk. A marked increase (53%; p < 0.001) in the nondialyzable fraction of urinary hydroxyproline was found in the fluoridetreated group. Total urinary hydroxyproline levels were unchanged. The increased fraction of urinary hydroxyproline is suggestive of increased bone collagen synthesis and is consistent with the finding of a diminished rate of bone loss in the fluoride-treated group (per cent change in bone density after 107 wk was ?0.14 ± 5.28 versus ?5.24 ± 7.62 for the placebo-treated group; p < 0.02). Serum alkaline phosphatase levels were elevated in the fluoride-treated group (38%; p < 0.001) after 107 wk of treatment. This change, as well as the increased fraction of urinary hydroxyproline persisted for at least 6 mo after cessation of fluoride treatment and was not temporally related to serum fluoride levels. No significant changes in serum parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and phosphorus were found after 1 yr of fluoride treatment. These findings suggest that fluoride does not alter serum 25-hydroxy-vitamin D and that the mechanism by which fluoride increases the rate of bone formation does not involve hyperparathyroidism.     

Seasonal variation in urinary excretion of cyclic AMP in healthy people

In a group of healthy young men and women the daily urinary excretion of cyclic adenosine 3', 5'-monophosphate (cAMP), calcium, hydroxyproline and the renal threshold phosphate concentration were evaluated at monthly intervals during 1 yr. A significant seasonal variation in cAMP urinary excretion was demonstrated, with a maximum occurring in spring and a minimum in winter. A clear annual rhythm was also observed when the other above parameters were considered. These findings are of importance in the interpretation of urinary cAMP values in clinical situations, and in the study of bone metabolism.     

Serum and urinary zinc in fulminant hepatic failure

Patients with chronic hepatic encephalopathy have been shown to have low serum zinc levels. Moreover, in a controlled study, significant improvement was seen in these patients on oral zinc supplementation. Information on zinc status in fulminant hepatic failure is insufficient. Serum and urinary zinc abnormalities were studied in 22 patients with fulminant hepatic failure (FHF) and they were compared with age- and sex-matched controls. The mean serum zinc values were significantly less in patients with FHF (72.7 +/- 3.7 micrograms/100 mL versus 107.9 +/- 6.2 micrograms/mL) while the urinary zinc values were significantly higher compared with controls (603.5 +/- 9.3 micrograms/24 h versus 334.4 +/- 10 micrograms/24 h). The serum zinc levels significantly and progressively decreased, while urinary zinc significantly increased after admission in patients with FHF. The serum zinc values in the group that survived were significantly higher than those in the group of patients who died. Correspondingly, urinary zinc was lower in survivors than in the group that expired. This study indicates that serum and urinary zinc levels could be used as a prognostic indicator in FHF. A therapeutic trial with zinc supplementation is justified in this group of patients.     

Paget's disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment.

Thirteen patients with Paget's disease of the bone were treated with subcutaneous injections of synthetic salmon calcitonin (SCT) for a mean period of 22 months at doses of 50-100 MCR units daily or 3 times a week. They manifested symptomatic improvement and significant reductions in serum alkaline phosphatase and urinary hydroxyproline excretion during SCT administration. Following discontinuation of SCT, symptomatic improvement was maintained in 10 patients for up to one year, whereas a recurrence of symptoms was seen in only 3 patients. The serum alkaline phosphatase generally showed a return toward pretreatment values 6 months after discontinuation of SCT, whereas urinary hydroxyproline remained depressed for up to a year.     

Effects of dichloromethylene diphosphonate on serum and urinary calcium in primary hyperparathyroidism

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, was evaluated for its ability to lower the serum and urinary calcium in 14 patients with primary hyperparathyroidism. The study was double-blind, placebo-controlled, and cross-over in design. All patients received 12 weeks of Cl2MDP (1600 mg daily) and 12 weeks of placebo in a randomized sequence. The average serum calcium was lowered by Cl2MDP from 11.5 +/- 0.1 mg/dL to 10.8 +/- 0.2 mg/dL (p less than 0.001). In the 3-month follow-up after drug administration, the average serum calcium (11.0 +/- 0.2 mg/dL) remained significantly below pretreatment levels (p less than 0.01). The reduction in serum calcium was accompanied by a significant decline in the urinary hydroxyproline excretion from 37 +/- 3 to 28 +/- 2 mg/g creatinine (p less than 0.01) and by a 40% reduction in the average urinary calcium excretion from 185 +/- 29 to 113 +/- 23 mg/g creatinine (p less than 0.01). Administration of Cl2MDP was not associated with any significant changes in parathyroid hormone levels or in urinary cyclic adenosine monophosphate excretion. No side effects were observed. We conclude that Cl2MDP lowers the serum and urinary calcium in patients with primary hyperparathyroidism.     

Is the aminoterminal propeptide of type III procollagen degraded in the liver? A study of type III procollagen peptide in serum during liver transplantation in pigs

The aminoterminal propeptide of type III collagen was monitored in serum during liver transplantation in nine pigs. The aim was to investigate whether removal of the liver causes any changes in the serum concentration of the propeptide. Another connective tissue component, hyaluronan, a glycosaminoglycan known to be degraded in the liver endothelial cells, was also measured. Removal of the liver caused a significant increase in the concentration of the intact propeptide as well as of hyaluronan. Gel filtration confirmed the increase in the amount of intact propeptide. However, another large propeptide-related antigen, eluted near the void volume, appeared in the antigen profile during the anhepatic phase. This peak probably represents the propeptide still attached to the collagen molecule (pN collagen). The findings indicate that the liver is involved in the degradation of the propeptide and of larger propeptide-holding proteins.