PubMed Health⌕ Search

Biomedical subjects

G Coen

Publications and source records attributed to G Coen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Intravenous versus oral calcitriol therapy in renal osteodystrophy: results of a prospective, pulsed and dose-comparable study.

Intravenous calcitriol is generally considered to be more efficient than oral administration in the treatment of secondary hyperparathyroidism of chronic renal failure, although a comparative and prospective study employing the same doses and modality of drug administration is lacking. We therefore evaluated 12 hemodialysis (HD) patients (51.7 +/- 9.4 years, mean +/- SD, HD for 8.7 +/- 4.7 years) with marked secondary hyperparathyroidism. Based on basal humoral and bone histologic parameters, we divided these patients into 2 comparable groups. Calcitriol (0.015 micrograms/kg) was given at the end of each dialysis intravenously in group A and orally in group B. Humoral parameters were evaluated basally and after 1, 2, 4 and 8 months. Ax bone biopsy was taken at the start and at the end of the study. From the first month of treatment, group A showed an increment in ionized calcium (from 1.28 +/- 0.08 to 1.37 +/- 0.12 mmol/l, p < 0.01), with a reduction in intact parathyroid hormone (from 470.1 +/- 349.5 to 255.5 +/- 256.5 pg/ml; p < 0.0003) and alkaline phosphatase (from 615.1 +/- 696.3 to 445.3 +/- 577.7 mU/ml, p < 0.001). The occurrence of hypercalcemia prompted a reduction in dialysate calcium content in 4 of 6 patients after 4 months, and of the calcitriol dose in 2 of 4 patients after 6 months. Ionized calcium then turned to 1.32 +/- 0.11 (p = n.s. compared to basal) while the intact parathyroid hormone concentration tended to revert (363.3 +/- 360 pg/ml, p = n.s. compared to basal) and alkaline phosphatase remained low (420 +/- 638 mU/ml, p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Two-site immunoradiometric intact parathyroid hormone assay versus C-terminal parathyroid hormone in predicting osteodystrophic bone lesions in predialysis chronic renal failure.

Intact parathyroid hormone (iPTH) radioimmunoassay represents an important advancement in the measurement of serum PTH levels, permitting the evaluation of the actual rate of secretion of the parathyroid glands. The aim of the study was to compare the value of intact and C-terminal PTH measurements in predicting the osteodystrophic bone lesion in predialysis patients with chronic renal failure (CRF). We have studied 37 subjects with CRF who were receiving conservative treatment. In each subject a transiliac bone biopsy for histomorphometric examination was performed in addition to the assay of serum intact and C-terminal PTH, osteocalcin, and alkaline phosphatase. Serum C-terminal and intact PTH levels were closely correlated, both showing a high degree of correlation with serum osteocalcin. Similar degrees of correlation were observed between the two PTH assays and the histologic parameters osteoblastic surface (ObS/BS) and osteoclastic surface (OcS/BS). The evaluation of specificity and sensitivity of the two PTH assays in selecting patients with normal or pathologic histomorphometric parameters gave an equivalent number of false positive and negative cases. Based on discriminant analysis of histomorphometric parameters, intact PTH shows a higher discriminant power when compared with C-terminal PTH assay for the parameters OcS/BS and eroded surface (ES/BS), but without practical clinical value. In conclusion, in analogy to the short lived N-terminal PTH fragment assay, prediction of elementary hyperparathyroid bone lesions in predialysis CRF is not improved by the use of intact PTH as compared to the more traditional C-terminal assay.

Adult↗
PubMed1993

Role of ageing, chronic renal failure and dialysis in the calcification of mitral annulus.

Mitral annulus calcification, a common lesion of the elderly (over age 60 years), has been detected with increased frequency and at younger ages in patients with uraemia. To date a pathogenic role for dialysis and secondary hyperparathyroidism has been suggested only on the basis of older dialytic age and increased serum iPTH observed in the affected individuals. Because this is a potentially dangerous lesion we deemed it useful to evaluate more completely the respective roles of possible pathogenetic factors in uraemic individuals. Evaluation included echocardiography, ECG, limb radiography, and serum assays. A total of 225 dialysis (HD) patients, 67 chronic renal failure (CRF) patients on conservative treatment and 67 normal subjects were studied. Mitral annulus calcification was detected in 87 of 225 (38.6%) HD patients, 11 of 67 (16.4%) CRF and six of 67 (8.9%) normals. In HD, patients with calcification were older and on longer-term renal replacement therapy compared to those without calcification. They also had greater values of iPTH, BGP, AP, and Rx score of secondary hyperparathyroidism. Mitral annulus calcification was associated more frequently (chi 2 = 14.8; P < 0.0001) with rhythm and cardiac conduction defects, but not with ectopic calcifications. Multiple stepwise regression analysis, with mitral annulus calcification score as dependent variable, selected dialysis duration, age, and iPTH (rm = 0.368) as the most predictive parameters, with the first two carrying most of the information. The stratification of patients according with these two parameters showed a progressive increase in the frequency of calcification both with HD duration and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Biologic effect of 1,24(R)(OH)2D3 versus 1,25(OH)2D3 administration in chronic renal failure.

1,24(R)(OH)2D3 is a synthetic analogue of 1,25(OH)2D3 which binds to the same receptors as the physiologic metabolite with a lower affinity. The aim of the present study was to compare the activity of 1,24(R)(OH)2D3 and 1,25(OH)2D3 on several target organs in patients with chronic renal failure. Treatment with 1,24(R)(OH)2D3 at doses of either 1 or 2 micrograms daily was carried out in two groups of 9 patients, with serum creatinine of 4.61 +/- 1.59 and 4.66 +/- 1.46 mg/dl, respectively. Doses of 1,25(OH)2D3 were 0.5 and 1 microgram daily and were administered to 9 and 13 patients, serum creatinine of 4.52 +/- 1.67 and 4.3 +/- 1.16 mg/dl, respectively. Treatment periods were of 2 weeks. Administration of 1,25(OH)2D3, 1 microgram, induced significant increments of intestinal calcium absorption (ICA), ionized calcium, osteocalcin, serum creatinine, urine Ca/GFR, and a decrease in iPTH. 1,25(OH)2D3, 0.5 microgram, induced a significant increase in ICA and osteocalcin and a decrease in iPTH. Similarly 1,24(OH)2D3, 2 micrograms daily, significantly stimulated ICA and raised serum levels of osteocalcin and creatinine while lowering serum iPTH. In addition, 1,24(R)(OH)2D3 administration induced a significant fall of serum 1,25(OH)2D3. Following 1 microgram, only osteocalcin increased. Therefore, the dose of 2 micrograms of 1,24(R)(OH)2D3 has biologic activity similar to 0.5 microgram 1,25(OH)2D3 (4:1). However the activity ratio on osteocalcin production appears to be 2:1. In addition, 1,24(R)(OH)2D3 is able to inhibit renal tubular 1 alpha-hydroxylase. In conclusion 1,24(R)(OH)2D3 may prove to be useful in the treatment of metabolic bone disease.

Adult↗
PubMed1992

Procollagen type I C-terminal extension peptide in predialysis chronic renal failure.

Collagen type 1 is the most abundant protein of bone. Serum levels of type 1 procollagen carboxy-terminal extension peptide (Procoll-1-C) may give a measure of the rate of synthesis of the collagen of bone and be therefore a marker of bone turnover. We have studied 38 patients with predialysis chronic renal failure; 14 of them were under long-term treatment with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for prevention of secondary hyperparathyroidism. In all patients a transiliac bone biopsy for histomorphometry and determination of dynamic parameters was performed following double tetracycline labeling. In addition serum Procoll-1-C, intact and C-terminal parathyroid hormone (PTH), osteocalcin and alkaline phosphatase were determined. In the patients not receiving 1,25(OH)2D3, serum levels of Procoll-1-C were higher than normal. Procoll-1-C did not correlate with any of the humoral parameters, including serum creatinine, nor with static histomorphometric parameters. Contrarily to osteocalcin, the collagen type 1 marker correlated significantly with all dynamic parameters. Treatment with 1,25(OH)2D3 was accompanied by lower levels of osteocalcin, iPTH (n.s.), osteoblastic surface and by normal levels of Procoll-1-C (p < 0.001, compared to untreated patients), without substantial change in bone formation parameters (bone formation rate). In conclusion Procoll-1-C in predialysis chronic renal failure is a marker of bone turnover unparalleled by other markers. 1,25(OH)2D3 administration is associated with lower serum levels of the peptide unaccompanied by a decrement of bone formation parameters, therefore with an apparently better utilization of collagen type 1 in the mineralization process.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1992

Deferoxamine test and PTH serum levels are useful not to recognize but to exclude aluminum-related bone disease.

The use of noninvasive diagnostic tools, like the deferoxamine (DFO) test and serum iPTH, to identify aluminum-related bone disease has proved to be inadequate due to false-negative cases; therefore, bone biopsy becomes a necessary diagnostic procedure. Our purpose was to verify whether these non-invasive parameters, appropriately used, may result valid in the identification of patients not at risk of Al toxicity, therefore restricting the need for histologic evaluation. We studied 68 hemodialyzed patients, aged 49.0 +/- 11.6 years, with a M/F ratio of 37/31 and a dialytic age of 85.0 +/- 47.0 months, by means of bone biopsy, DFO test and serum C-PTH. 19.1% of the cases had positive stainable Al and/or high bone Al content (greater than 60 mg/kg/dw) and could be intoxicated. To obtain the highest sensitivity, we selected the following limit values: the lower limit of increment so far proposed for DFO test positivity (greater than 150 micrograms/l) and a value capable of selecting patients with pathologic osteoclasia for C-PTH (greater than 15 ng/ml). With these limits, four different groups of patients were recognized: group A, DFO test positive and PTH high, n = 12; group B, DFO test positive and PTH low, n = 6; group C, DFO test negative and PTH high, n = 30; group D, DFO test negative and PTH low, n = 20. In group B, which could be anticipated as being at higher risk, we actually found the highest (p less than 0.05) bone Al content as compared to other groups, associated with a reduced bone formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Plasma insulin-like growth factor-1 and bone formation parameters in predialysis chronic renal failure.

Insulin-like growth factor-1 (IGF-1), produced by osteoblasts following parathormone (PTH) stimulation, is a local hormone with autocrine and paracrine functions on bone formation. To evaluate whether circulating IGF-1 is also important in stimulating bone formation, a study was carried out on 28 patients with slowly progressing nondialytic chronic renal failure. 9 patients were treated with 1,25(OH)2D3, while 19 did not receive vitamin D metabolites. In all patients a transiliac bone biopsy for histomorphometric studies was obtained, and the following determinations were made: immunoreactive PTH (iPTH), osteocalcin, alkaline phosphatase, IGF-1, serum calcium, phosphate and creatinine. Serum IGF-1 levels were similar in the two groups of patients, and higher than normal. iPTH and osteocalcin were positively correlated with serum creatinine, osteoblast surface and the eroded surface, but did not correlate with IGF-1. A negative (n.s.) relationship was found between dynamic bone parameters and circulating IGF-1, with the mineral apposition rate reaching a significant level (p less than 0.05). In conclusion, the circulating levels of IGF-1 are not correlated with bone formation parameters, thus apparently showing no role in bone turnover or dependency on bone production of the growth factor. The results may favor the hypothesis of a negative feedback control of circulating IGF-1 by suppressive signals originating from active bone metabolic units.

Aged↗
PubMed1990

Autonomic neuropathy and secondary hyperparathyroidism in uremia.

To evaluate the relationship between autonomic neuropathy, and biochemical and radiological parameters of secondary hyperparathyroidism, we examined 19 predialysis and 24 hemodialysis non-diabetic uremic patients. Autonomic neuropathy was assessed using four cardiovascular tests. Ten predialysis and 15 hemodialysis patients showed abnormalities in one or more autonomic tests. Ca, Ca2+, P, alkaline phosphatase, immunoreactive parathyroid hormone and osteocalcin did not significantly differ in uremic patients with and without abnormal autonomic test results. Radiological markers of hyperparathyroidism such as acro-osteolysis (score A) and subperiosteal resorption (score B) were more common in patients with abnormalities in autonomic tests than in patients without. When predialysis and hemodialysis patients were considered separately, the correlation between score A, score B and autonomic neuropathy was confirmed only in hemodialysis patients. In conclusion, autonomic neuropathy is not related to biochemical parameters of hyperparathyroidism, while it appears correlated with radiological signs of osteodystrophy, suggesting a possible pathogenetic link between autonomic neuropathy and secondary hyperparathyroidism.

Adult↗
PubMed1990

Autonomic neuropathy and secondary hyperparathyroidism in uraemia.

To evaluate the relationship between autonomic neuropathy, and biochemical and X-ray parameters of secondary hyperparathyroidism, we examined 19 predialysis and 24 haemodialysis non-diabetic uraemic patients. Autonomic neuropathy was assessed using four tests: deep breathing, Valsalva manoeuvre, lying to standing, and postural hypotension. Serum Ca, Ca2+, P, Mg, alkaline phosphatase, iPTH, and osteocalcin were assayed. Hand X-ray was obtained to evaluate acro-osteolysis (score A) and subperiosteal resorption (score B). Ten predialysis patients (52%) and 15 haemodialysis patients (62%) showed one or more abnormal autonomic tests. Age, dialysis duration, and biochemical parameters of secondary hyperparathyroidism did not differ significantly in uraemic patients with and without abnormal autonomic tests. Furthermore, there was no significant relation between autonomic tests and iPTH or osteocalcin. Score A and score B was significantly greater in patients with abnormal tests than in patients without (P less than 0.009 and P less than 0.025). When predialysis and haemodialysis patients were considered separately the correlation between score A, score B, and autonomic neuropathy was confirmed only in haemodialysis patients. In conclusion, autonomic neuropathy does not seem to be related to the biochemical parameters of secondary hyperparathyroidism, while it appears significantly associated with the radiological signs of osteodystrophy, suggesting a possible pathogenetic linkage between autonomic neuropathy and secondary hyperparathyroidism.

Adult↗
PubMed1990

Osteocalcin, iPTH, alkaline phosphatase and hand X-ray scores as predictive indices of histomorphometric parameters in renal osteodystrophy.

To evaluate the relationship between hyperparathyroid bone X-ray lesion, biochemical parameters and bone histology in chronic renal failure, 59 patients (52 +/- 14.9 years; Crs 4.7 +/- 2.2 mg/dl, mean +/- SD) on conservative treatment and 103 (48 +/- 14 years) on hemodialysis (from 48.4 +/- 36.7 months) were studied. Right-hand X-ray was carried out for evaluation of the scores (0-3) of acroosteolysis (score A) and subperiosteal resorption (score B). Serum iPTH, osteocalcin and alkaline phosphatase (AP) were measured. In addition in a subset of 53 patients, 30 in predialysis and 23 in dialysis, a bone biopsy was performed for histomorphometry. In predialysis the scores A and B correlated with bone GLA protein (BGP) (p less than 0.01), AP (p less than 0.05) and osteoid surface (p less than 0.05) and 0.01 respectively). In hemodialysis the same level of significant correlation (p less than 0.001) was found between the scores and the three humoral parameters. Score A correlated with active osteoblastic surface and active resorption surface while score B correlated with active osteoblastic surface (p less than 0.01), osteoid surface and active resorption surface (p less than 0.05). Multiple regression analysis carried out to establish the predictive variables of bone histologic lesions (active resorption surface and active osteoblastic surface) singled out BGP in predialysis and AP and the two scores in dialysis. We conclude that serum BGP, as compared to PTH and AP, prevails as a valid marker of hyperparathyroid bone lesion in predialysis, while in dialysis it does not seem to add further information to that carried by other variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Aztreonam and aminoglycosides in the therapy of urinary infections associated with renal calculosis].

Renal calculosis associated with urinary tract infections due to urease-positive or -negative microorganisms poses difficult therapeutic problems. The introduction of monobactam antibiotics such as aztreonam offers a valid therapeutic alternative thanks to the action of this drug on the gram-negative organism often at the root of these infections. The above study has been carried out in 10 patients with infections due to organisms sensitive to aztreonam and aminoglucosides. Treatment with aztreonam (1 g i.m. 3 times daily) brought about sterilization lasting from 3 weeks to permanently in 5 cases. In one case sterilization was transitory and in 4 cases treatment was unsuccessful. Creatinine blood level and other biochemical parameters did not vary. Aminoglucosides alone brought about transitory sterility in 2 cases and was unsuccessful in 6. At the end of treatment, creatinine blood level had increased significantly. Given the absence of toxicity the definitely better therapeutic result, and the absence of induced resistance, aztreonam should be considered the drug of choice and should be preferred to aminoglucosides for the management of urinary tract infections due to microorganisms sensitive to both types of drugs in patients with urinary calculosis.

Adolescent↗
PubMed1989

Use of a gonadotropin-releasing hormone agonist during ovarian stimulation leads to significant concentrations of peptide in follicular fluids.

The penetration of a gonadotropin-releasing hormone agonist (GnRH-a), Buserelin (Hoechst AG, Frankfurt, West Germany), into human follicular fluids (FF) was studied by means of a radioimmunoassay (RIA) and a bioassay. Acute nasal administration of a therapeutic dose of Buserelin (300 and 600 micrograms) before the ovum pickup for in vitro fertilization leads to significant concentrations of Buserelin in one-third of the FF. These concentrations ranged between 28 and 124 pg/ml, which represents 10% to 50% of the serum concentrations achieved in these patients. Follicular penetration of this agonist is time-dependent. Chronic administration during the follicular phase leads to low but significant concentrations of peptide 36 hours after the last inhalation. A very good correlation was observed between the RIA and the bioassay. This demonstrates the accuracy and the specificity of the RIA. In addition, it indicates that the Buserelin that reaches follicles is intact and is not the inactive product of degradation. Intranasal administration of Buserelin stopped 35 hours before ovum pickup appears to be an adequate way of minimizing the exposure of maturing oocytes to the GnRH-a.

Adult↗
PubMed1989

Severe vitamin D deficiency in a case of primary hyperparathyroidism caused by parathyroid lipoadenoma, effect of 25OHD3 treatment.

This report describes the case of a 60-year-old woman with severe metabolic bone disease and fractures due to vitamin D deficiency and hyperparathyroidism. 25OHDH3 and 1,25(OH)2D3 serum levels were undetectable and increased immediately following 25OHD3 oral administration. Serum 1,25(OH)2D3 following vitamin D repletion reached values above the normal range, and remained elevated with strict dependence on the serum 25OHD3 levels. Parathyroid hormone and alkaline phosphatase decreased during treatment, without reaching normality during 1 year of observation. Bone biopsies before and after 8-month 25OHD3 treatment showed disappearance of the osteomalacic and hyperparathyroid lesions. During treatment an increase in serum and urine calcium and formation of renal stones were observed. The patient underwent neck exploration with the finding and removal of a lipoadenoma, a rare parathyroid tumor, followed by complete and permanent remission of the disease. In conclusion, this case is suggestive of the key role played by the long-term vitamin D status in the clinical expression of primary hyperparathyroidism.

Adenoma↗
PubMed1989

Bone aluminum content in predialysis chronic renal failure and its relation with secondary hyperparathyroidism and 1,25(OH)2D3 treatment.

32 patients with slowly evolving predialysis chronic renal failure, who were not exposed to aluminum-containing antacids, were studied. A low aluminum intake was considered a useful condition to examine the bone deposition of the element as dependent variable, not interfering with PTH secretion and bone metabolism. Iliac bone biopsies for bone aluminum content and histomorphometric and histodynamic evaluations were taken. Serum aluminum, creatinine, calcium, phosphate, iPTH, osteocalcin (BGP), alkaline phosphatase (AP), 25-OHD3 and 1,25(OH)2D3 were also measured. 16 of the patients were on long-term treatment with 1,25(OH)2D3 (0.25 micrograms daily) for prevention and treatment of secondary hyperparathyroidism. Bone aluminum content of all patients showed a strong positive correlation with BGP and iPTH (p less than 0.001) while the correlation with serum creatinine was not significant. Multiregression analysis has singled out BGP as the most predictive variable of bone aluminum content (r2 = 0.419). The patients receiving 1,25(OH)2D3 had lower iPTH (p less than 0.01), lower bone aluminum content (p less than 0.05) and increased mineral apposition rate (p less than 0.05) compared to the untreated group. The results suggest that treatment with 1,25(OH)2D3 for long-term suppression of secondary hyperparathyroidism does not enhance aluminum accumulation in bone. The finding of lower bone aluminum together with increased mineral apposition rate, seems to indicate that 1,25(OH)2D3 is able to induce an osteoid mineralization process more selective against aluminum incorporation in bone than in case of more severe hyperparathyroidism and 1,25(OH)2D3 deficiency. At least in the present condition of low aluminum intake, 1,25(OH)2D3 may be considered to have protective effects on bone from aluminum deposition.

Adult↗