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Biomedical subjects

J L Sebert

Publications and source records attributed to J L Sebert.

At least 91 records · Page 5Linked to original sources

[Stages of the etiological diagnosis of hypercalcemia].

After confirming hypercalcemia by 3 successive measurements of the total plasma calcium corrected for a plasma protein concentration of 72 g/l, which excludes spurious hypercalcemia due to dehydration, the physician orientates the aetiological diagnosis bearing in mind that primary hyperparathyroidism PHPT is the cause of 85 p. 100 of all asymptomatic forms of hypercalcaemia whilst overt or occult malignancy is the main cause (60 p. 100) of symptomatic forms of hypercalcaemia with PHPT responsible for 20 p. 100 of cases. Other causes, including drug toxicity with Vit D, calcium, Vit A, lithium, thiazide and aluminium hydroxide, sarcoidosis, hyperthyroidism, Addison's disease, pheochromocytoma and familial endocrine disorders are much rarer. Nevertheless, these rarer causes must be excluded on the clinical history and examination followed by radiological (chest X ray, plain abdomen X ray, bone X rays) and simple biological tests. The latter and/or scans tests should also help in a rapid diagnosis of metastatic carcinoma and multiple myeloma, so that the major diagnostic problem is to distinguish primary HPT from occult malignancy. This problem is greatly facilitated by reliable assays of C terminal or medium PTH rather than renal CAMP which is increased in 80 p. 100 of occult malignancies. When PTH assays is unavailable or unreliable Dent's hydrocortisone suppression test may be useful as a fall in'serum calcium is associated with occult malignancy in 70 p. 100 of cases and non-suppression is associated with PHPT in 91 p. 100 of cases. Discriminant analysis of the usual biochemical parameters may be helpful in this differential diagnosis and is accurate in about 90 p. 100 of cases. However, the association of PHPT and malignancy is also possible and not fortuitous.

Humans↗

[Hypercalcemia with elevation of parathormone in lymphocytic lymphoma. Efficacy of ethanehydroxydiphosphonate by mouth].

Acute hypercalcaemia was observed in a 54 year old woman followed up over a five year period for a lymphocytic non-Hodgkin lymphoma, a complication which is rare in chronic lymphoproliferative disorders except multiple myeloma. This case is of interest from 3 points of view: haematological: the simultaneous occurrence of hypercalcaemia (4.80 mmol/l) and of a leukaemic phase (19,300 lymphocytes/mm3) with no signs of "transformation" of the haemopathy; physiopathological: increased osteoclastic bone resorption and a rise in serum parathormone (0.21 to 4.82 ng/ml); therapeutic: efficacy of oral ethane 1, hydroxy 1, 1 diphosphonate (20 mg/kg/day) in treating the hypercalcaemia.

Bone Resorption↗

The desferrioxamine test predicts bone aluminium burden induced by A1(OH)3 in uraemic patients but not mild histological osteomalacia.

Desferrioxamine (DFO), a chelating agent of aluminium was administered to 27 uraemic patients on chronic haemodialysis or haemofiltration with a minimal parenteral exposure to aluminium but taking various amounts of A1(OH)3 for about two years. All these patients had a double bone biopsy for measurement of their aluminium content and histomorphometric evaluation. Bone aluminium of our patients were 10 times greater than in our uraemic controls. Plasma aluminium increase (delta A1) induced by DFO correlated better than basal plasma aluminium with bone aluminium and cumulative dose of A1(OH)3 correlated with bone aluminium and delta A1 DFO. None of the patients had florid osteomalacia and only two had traces of aluminium staining. However 16 had mild mineralisation defect as demonstrated by low mineral appositional rate. The aluminium parameters were not different between the two groups of patients with or without mild mineralisation defect. It is concluded that the DFO test predicts bone aluminium but not mild histological osteomalacia in uraemic patients moderately aluminium over-loaded with phosphate binders.

Aged↗

Influence of biochemical and hormonal factors on the bone histomorphometric features of uraemic patients.

A multidimensional analysis was used to evaluate, the influence on bone histology of various biochemical and hormonal factors in 20 uraemic patients on chronic haemodialysis or haemofiltration. A positive relationship (p less than 0.1) was found between PTH and osteoclastic and osteoblastic surfaces but not with mineral apposition and bone formation rates. The mineral appositional rate which reflects the cellular activity of osteoblasts was positively related to D metabolites 25(OH)D3 and 1,25(OH)2D3 and to phosphate (p less than 0.1). Mineral appositional rate and bone formation rate were negatively related to bone aluminium (p less than 0.05). These data indicate that: 1) PTH simulates bone turnover but has no direct effect on the bone cellular activity of osteoblasts which is mainly dependent on D metabolites and phosphate; 2) mild aluminium overload not severe enough to cause osteomalacia decreases bone formation in uraemic patients. This study evaluates the role of various simultaneously measured biochemical and hormonal factors on bone histological parameters in uraemic patients.

Adult↗

[Primary hyperparathyroidism. Lack of effect of cimetidine on plasma levels of parathyroid hormone and calcium].

Because of the contradictory results formerly published as regards the effect of cimetidine in primary hyperparathyroidism, we have studied the effect of cimetidine at the daily dose of 1200 mg in 14 cases of primary hyperparathyroidism. The diagnosis was ascertained in all cases by the coexistence of an otherwise unexplained hypercalcemia and of a concomitantly elevated plasma concentration of immunoreactive parathyroid hormone (PiPTH) measured by 2 different antibodies and confirmed in 10 cases by surgical neck exploration. In 5 cases with severe hypercalcemia (greater than 12.0 mg/l) cimetidine was discontinued after 5 days because of its lack of effect on both plasma concentrations of calcium and PiPTH, and the patients were successfully operated. In 8 cases with milder hypercalcemia, cimetidine was given for 1.5-6 months. There was no significant change in both plasma concentrations of calcium (PCa) and PiPTH but a regression analysis showed that PCa was negatively correlated to time with a correlation coefficient which would have become significant if the follow-up had been 9 months. In the last patient severe hypercalcemia was controlled by simultaneous administration of phosphate, indomethacin and cimetidine without concomitant decrease of PiPTH; and 6 weeks after cimetidine discontinuation no significant increase of PCa and PiPTH occurred. These data show that cimetidine has no clinically therapeutic value in primary hyperparathyroidism.

Adolescent↗

Advantage of hand bone calcium content measurement by local neutron activation analysis for following up hemodialysis patients.

Hand bone calcium content [Ca] has been measured by local neutron analysis in hemodialyzed patients free of signs of osteomalacia before and 6-12 months after treatment with vitamin D metabolites, and it has been compared to some iliac bone histomorphometric parameters. With 1,25-(OH)2D3 alone, [Ca] increases significantly at the 6th month of treatment (p less than 0.001) but not from the 6th to the 12th month. With 1 alpha-(OH)D3 + 25-(OH)D3 the same phenomenon is observed at the 6th and 12th months of treatment. Before treatment, [Ca] was correlated negatively with the osteoid surfaces (OS) (r = -0.62, p = 0.01) and the number of osteoclasts per square millimeter (Ocl/mm2) (r = -0.79, p less than 0.001). At the 6th month of treatment, [Ca] was still correlated negatively with OS (r = -0.42, p = 0.05) and with Ocl/mm2 (r = -0.60, p less than 0.005). At the 12th month, the two negative correlations decreased but remained significant (r = -0.42, p = 0.05; r = -0.45, p = 0.05). These data suggest that (1) hand bone calcium analysis by neutron activation permits to follow up the peripheral bone mineral content in hemodialyzed patients and (2) the [Ca] increase only observed during the first months of treatment with vitamin D metabolites probably result from an attenuation of secondary hyperparathyroidism.

Adult↗

[Singh femoral index in vertebral osteoporosis].

In 48 patients with osteoporosis and at least one vertebral fracture, the Singh vertebral index, which assesses the femoral trabeculation, was compared to the Meunier vertebral radiologic index, which is determined according to the number and severity of vertebral deformations. The femoral index was abnormal in all patients. However, the threshold level, set by Singh at Stage IV, which supposedly discriminates between subjects with and without osteoporosis could not be confirmed as one-third of the patients with at least one vertebral fracture were Stage V. A statistically significant correlation was found between the femoral index and the vertebral radiological index.

Aged↗

Possible link between changes in plasma 24,25-dihydroxyvitamin D and healing of bone resorption in dialysis osteodystrophy.

Histomorphometric studies of bone biopsies were performed on 12 hemodialyzed patients before and after six months of treatment with 25-(OH) and 1 alpha-(OH) vitamin D3. Patients could be classified into three groups according to bone resorption: Group I with normal bone resorption; Group II with elevated initial bone resorption unresponsive to vitamin D treatment; group III with elevated initial bone resorption sensitive to vitamin D treatment. None of the patients had histological signs of osteomalacia. In Group I, plasma concentrations of 24,25-(OH)2D and the ratio of 24,25-(OH)2D to 25-(OH) D remained in the normal range throughout the study; in Group II these parameters were subnormal initially and did not increase above normal except in one case; in Group III, plasma concentrations of 24,25-(OH)2D were high before or at the beginning of vitamin D administration and normal at the time of the second biopsy and wide variations were observed in the ratio of 24,25-(OH)2D to 25-(OH)D. No difference was found between these last two groups with regard to the cumulative dose of vitamin D derivatives administered or the changes in plasma PTH, CT, calcium and phosphate. These observations suggest a specific regulation of plasma 24,25-(OH)2D concentrations in hemodialyzed patients and a possible link (independent of circulating PTH, CT, or phosphate) between this regulation and healing of bone resorption. However, no correlation was found between plasma 24,25-(OH)2D and either one of the simultaneously measured biochemical or histological parameters.

24,25-Dihydroxyvitamin D 3↗

[Does 24,25 dihydroxycholecalciferol have a physiological and pathophysiological role?].

The authors review recent experimental and human data concerning the potential physiological and pathophysiological role of 24,25 (OH)2D3, the dihydroxylated metabolite of vitamin D which is synthetisized with preference over 1,25 (OH)2D3 in organisms that have been replenished with vitamin D. For the major known effects of vitamin D such as stimulation of intestinal absorption and bone resorption of calcium and phosphorus, 24,25 (OH)2D3 is less effective than the 1,25 (OH)2D3 metabolite and consequently of lesser physiological importance. Some recent in vitro experiments have shown, however, that 24,25 (OH)2D3 intervenes in the stimulation of proteoglycan synthesis, inhibition of PTH, vitamin A and heparin induced resorption, whereas 1,25 (OH)2D3 does not. Although there is controversy as to its direct inhibitory effect on secretion of PTH, it seems to act with 1,25 (OH)2D3 to prevent hyperplasia of parathyroids in vitamin D deficient chicken. From a pathophysiological point, the presence of 24,25 (OH)2D3 seems vital to allow normal bone formation and mineralisation and possibly to counteract excessive bone resorption.

24,25-Dihydroxyvitamin D 3↗

Cimetidine and circulating calciotropic hormone levels in uremic patients: evidence for a suppressive effect on calcitonin secretion.

The effect of oral cimetidine on parathyroid hormone and calcitonin plasma levels was evaluated in 12 uremic patients on chronic hemodialysis. Compliance to treatment was monitored by measuring cimetidine plasma concentrations. Plasma cimetidine was measurable in 7 patients and undetectable in 5. In compliant patients, there was no change in plasma concentration of calcium and parathyroid hormone but a significant fall of 75% in plasma calcitonin levels during treatment, followed by an increase towards initial values after cimetidine discontinuation. No significant change occurred in the other 5 patients. Cimetidine therefore appears to be of little value in the treatment of uremic hyperparathyroidism.

Adult↗

[Fasting urinary excretion of calcium, phosphorus and hydroxyproline in relation to creatinine. Normal values and correlations with 24-hour urine values (author's transl)].

The ratios to creatinine of calcium (Ca/Cr), phosphorus (P/Cr) and hydroxyproline (HOP/Cr) were determined in samples of urine collected during a 2-hour period in fasting subjects. Normal values (mean +/- s.d.) of Ca/Cr (0.134 +/- 0.067), P/Cr (0.048 +/- 0.15) and HOP/Cr (0,017 +/- 0,007) obtained in 50 healthy subjects were in agreement with those previously reported by Nordin. The 2-hour urine collection is technically simpler than the conventional 24-hour urine collection, does not expose to the errors inherent in minuted urine collection and provides more information on bone diseases.

Bone Diseases, Metabolic↗

Effect of propranolol and metoprolol on parathyroid hormone and calcitonin secretions in uraemic patients.

Nine uraemic patients not being treated by dialysis received intravenous propranolol 1 microgram/kg/min for 85 minutes after a priming dose of 1 mg. Fifteen days later, six of them received intravenous metoprolol 1.2 microgram/kg/min after a priming dose of 1.2 mg. Plasma concentrations of parathyroid hormone (PTH) and calcitonin fell significantly after propranolol but not after metoprolol, whereas no change in plasma concentrations of ionised calcium and phosphate occurred with either drug. Heart rate fell similarly with both drugs. The fact that propranolol acutely suppressed PTH and calcitonin secretion in uraemic patients indicates that further studies are warranted to assess the long-term effects of the drug on the secretion of these hormones and on renal osteodystrophy. The contrast between the responses to propranolol and metoprolol supports the concept that PTH and calcitonin secretion is modulated through specific beta 2-receptors.

Adult↗