Inflammatory cytokine response in patients with septic shock secondary to generalized peritonitis.

OBJECTIVES: The aims of this study were the following: a) to assess the proinflammatory cytokine (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1, and IL-6) response in patients with septic shock secondary to generalized peritonitis; and b) to evaluate the influence of bacteremic status, type of peritonitis (acute perforation or postoperative), and peritoneal microbial status (mono- or polymicrobial) on cytokine expression and mortality. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifty-two consecutive patients with septic shock caused by generalized peritonitis. INTERVENTIONS: Routine blood tests, blood cultures, and cytokine assays were performed during the first 3 days after onset of shock. MEASUREMENTS AND MAIN RESULTS: Serum TNF-alpha and IL-6 concentrations were measured by using a radioimmunoassay, and IL-1 concentrations were measured by using ELISA. Median serum concentrations on day 1 were: TNF-alpha, 90 pg/mL; IL-1, 7 pg/mL; and IL-6, 5000 pg/mL. TNF-alpha and IL-6 concentrations decreased significantly between the first and third days of septic shock (p = .0001), whereas IL-1 concentrations remained low. The decrease in IL-6 tended to be more pronounced in the survivors group (p = .057). Median TNF-alpha serum concentrations were higher in bacteremic compared with nonbacteremic patients (151 vs. 73 pg/mL, p = .003). TNF-alpha, IL-1, and IL-6 serum concentrations and mortality were not different between acute perforation vs. postoperative peritonitis and mono- versus polymicrobial peritonitis. CONCLUSIONS: The systemic release of TNF-alpha and IL-6 during septic shock caused by generalized peritonitis was maximal on day 1 and decreased rapidly during the next days. No systemic release of IL-1 was observed. IL-6 serum concentrations remained higher in patients who subsequently died. Among the different features of peritonitis studied, only bacteremia influenced the systemic cytokine response (higher TNF-alpha).

Morphine-induced sensitization of locomotor activity in mice: effect of social isolation on plasma corticosterone levels.

This study examined the influence of social isolation on behavioural sensitization to the locomotor effect of morphine and the link between this behaviour and plasma corticosterone concentrations. Four weeks isolation induced an increase in the locomotor effect of morphine. In social and isolated mice, repeated administrations (6) of morphine (one injection every 3 or 4 days) followed by 3 h in an actimeter induced behavioural sensitization to the locomotor effect of morphine. No interaction was observed between social isolation and behavioural sensitization to morphine. Resocializing previously isolated mice for 3 weeks reduced the morphine-induced locomotor effect without altering the behavioural sensitization. Corticosterone plasma levels were more increased (416%) in mice isolated 5 weeks than in mice isolated for 2 weeks (243%) and they return to the control levels following 3 weeks of resocialization. Since there was no interaction between the increase in morphine locomotor effect induced by social isolation and the morphine-induced behavioural sensitization, it is suggested that each of these two events acts independently. Whether or not a common mechanism (plasma corticosterone levels?) partly underlies both effects, the result resembles a simple additive effect.

[Large cell variant of small cell carcinoma of the ovary with hypercalcemia]. / Variante à grandes cellules d'un carcinome à petites cellules de l'ovaire avec hypercalcémie.

We describe an original distinct type of ovarian small cell carcinoma: large cell variant. The distinctive histologic features of tumor cells were the presence of large nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry revealed strong diffuse vimentin, smooth muscle actin positivity and slight reactivity with epithelial markers. Electron microscopy showed aggregates of intermediate filaments, intercellular attachments and no dense core granules. This tumor is associated with paraendocrine hypercalcemia in two thirds of cases. Parathyroid hormone-related protein was focally positive. This tumor is characterized as a very lethal neoplasm, occurring primarily in young women.

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake.

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.

[Relative depletion in native vitamin D: a potential risk factor in Algerian hemodialysis patients with radiological evidence of hyperparathyroidism and osteomalacia independent of calcitriolemia]. / La déplétion relative en vitamine D native: un facteur de risque potentiel chez l'hémodialysé algérien de lésions radiologiques d'hyperparathyroïdie et d'ostéomalacie indépendant de la calcitriolémie.

Looser striae on the ischio-pubian branches and subperiosteal resorption of the phalanges were looked for in 113 chronic hemodialysis patients at the University Hospital of Annaba (Algeria) and were found in respectively 14 and 48 patients. Comparison of patients with and without radiological complications showed no significant difference in their age, sex ratio, nature of initial kidney disease and duration on dialysis. The patients with Looser striae had lower plasma levels of 25OHD3 than those without striae, whereas all other plasma parameters were similar. The plasma concentrations of intact PTH were higher in patients with resorption; these patients had lower plasma concentrations of calcium, bicarbonate, aluminum and 25OHD3 but similar plasma concentrations of phosphate and 1,25(OH)2D3. Multivariate analysis showed that PTH concentrations were independently linked only to plasma 25OHD3 (negatively) and duration on dialysis (positively). The results of this transversal study are in agreement with the well established pathophysiological roles of PTH hypersecretion, hypocalcemia and acidosis in the appearance of radiological hyperparathyroidism in hemodialysis patients. Furthermore they suggest that a relative native vitamin D deficiency may have a calcitriol independent role in favoring the occurrence of both osteitis fibrosa and osteomalacia.

High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: a prospective study in 59 patients.

BACKGROUND: In several studies including patients with septic shock of various origins, high serum cytokine levels have been reported to correlate with poor outcome. The aim of this prospective study was to assess the prognostic value of cytokine serum levels in a group of patients with perioperative septic shock of digestive origin. METHODS: From January 1992 to December 1994, 59 patients were evaluated (mean age, 68 +/- 15 years). From the first day of septic shock to day 7, blood was drawn every day to measure the conventional biologic parameters (white blood cell count, platelet count, hematocrit, blood urea nitrogen level, serum electrolytes level, pH, blood gases, serum lactate level, coagulation parameters, liver function tests) and tumor necrosis factor (TNF), interleukin-1, and interleukin-6. RESULTS: No difference was observed between the 26 survivors and the 33 nonsurvivors with regard to age, gender, and cause of sepsis. On admission, mean platelet count was significantly higher in the survivors than in the nonsurvivors (260 +/- 142 versus 177 +/- 122 10(9)/L; p = 0.01). Mean blood urea nitrogen level was significantly lower in the survivors than in the nonsurvivors (9.6 +/- 9 versus 12 +/- 7 mmol/L; p = 0.04). No difference was observed between survivors and nonsurvivors for the other conventional biologic parameters and for serum interleukin-1 and interleukin-6 levels. Mean serum TNF level tended to be higher in survivors than in nonsurvivors (565 +/- 1325 versus 94 +/- 69 pg/ml; not significant). In the group survivor 9 (35%) of 26 patients had a serum TNF level greater than 200 pg/ml versus 2 (6%) of 33 patients in the nonsurvivor group (p < 0.02). Survival was noted in 6 (100%) of 6 patients who had both a serum TNF level greater than 200 pg/ml and a platelet count greater than 100.10(9)/L versus 1 (11%) of 9 in patients with neither of these criteria (p < 0.01). CONCLUSIONS: In our patients with abdominal septic shock, high serum TNF levels were associated with increased survival. The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. Although this possibility must be further explored, a score combining the serum TNF level and platelet count could be helpful for the prognostic assessment of patients with abdominal septic shock.

1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone related protein secretion.

Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3. In vivo bone resorption was concomitantly assessed by histomorphometry on femoral neck bone sections. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultured in the presence of 1,25(OH)2D3 correlated with the number of osteoclasts measured on the bone femoral neck biopsies (r = 0.65, p < 0.01), suggesting that the formation of multinucleated cells in vitro could reflect the osteoclast differentiation in vivo. Furthermore, the number of osteoclasts was related to the eroded volume and the trabecular separation of the femoral neck bone biopsies. Finally, the release of interleukin-1 (IL-1), IL-6, and TNF-alpha by cultures of peripheral blood mononuclear cells (PBMC) and MMNC was measured by radioimmunoassay. The cytokine levels of basal and 1,25(OH)2D3-treated MMNC decreased from days 2 to 5 and then reached a plateau to day 10. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultures correlated with the basal IL-6 release in the same cultures determined at day 2 (r = 0.55, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines.

Increased bone resorption is a mechanism contributing to bone loss in the postmenopausal period. Cytokines are involved in osteoclastic differentiation and, therefore, may play a role in the regulation of bone resorption. Several previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This study determines the concomitant production of the three cytokines and tests the bone-resorbing activity of peripheral monocyte supernatants. Four groups of women were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr). Assignment to clinical groups was verified by plasma FSH and estradiol determinations. Lumbar spine bone mineral density was significantly higher in the premenopausal women group than in the three postmenopausal groups. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma, and after stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were measured by RIA in the monocyte surpernatants. The three cytokines were highly correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The mean levels of the three cytokines could not be compared because of the variations in the values. However, a trend toward lower levels in the three cytokines was noted in estrogen-treated women compared to the untreated postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed by fetal long bone-resorbing assay, increased in untreated postmenopausal compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P < 0.05). In estrogen-treated patients, this activity decreased to premenopausal levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor antagonist and TNF alpha antibodies to the supernatant bone culture medium induced a significant decrease in the calcium release. Those data show the involvement of several cytokines in the bone resorption process after estrogen deficiency.

In vitro production of cytokines by bone surface-derived osteoblastic cells in normal and osteoporotic postmenopausal women: relationship with cell proliferation.

To evaluate the role of cytokines produced by osteoblasts in the pathophysiology of bone lesions in postmenopausal osteoporosis (PMOP), we have determined by RIA and immunoradiometric assays the levels of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1), tumor necrosis factor-alpha (TNF alpha), and IL-6 released by cultured bone surface-derived osteoblastic (OB) cells isolated from 24 untreated PMOP women with high, low, or normal bone turnover on bone biopsy. OB cells isolated from patients with high bone formation had a 2-fold increased proliferation rate in vitro compared to OB cells from patients with normal or low bone formation or OB cells from age-matched controls. The spontaneous in vitro production per cell protein of PGE2, IL-1, and TNF alpha, but not of IL-6, was 2- to 3-fold lower in rapidly proliferating OB cells isolated from PMOP patients with high bone formation compared to OB cells from patients with normal or low proliferation or control cells. Treatment with 10 nmol/L 1,25-dihydroxyvitamin D (48 h) increased PGE2 levels to normal values in OB cells with a high proliferation rate, but decreased PGE2 production in cells with low proliferation and in control cells, suggesting that the release of PGE2 was dependent on the stage of maturation of OB cells. Significant correlations were found between IL-1 and TNF alpha (r = 0.87; P < 0.001), IL-1 and PGE2 (r = 0.46; P < 0.05), IL-6 and IL-1 (r = 0.39; P < 0.05), and IL-6 and TNF alpha (r = 0.49; P < 0.05), suggesting that the production of these cytokines was under reciprocal control. The results indicate that the in vitro production of PGE2, IL-1, and TNF alpha, but not IL-6, by OB cells isolated from patients with PMOP is related to the proliferation rate of these cells and the rate of bone formation. The variable production of cytokines by OB cells may contribute to the histological heterogeneity of bone formation in PMOP.

Comparison of intact, midregion, and carboxy terminal assays of parathyroid hormone for the diagnosis of bone disease in hemodialyzed patients.

The predictive value of three different RIAs of PTH for the diagnosis of the histological type of bone disease has been compared in 24 asymptomatic patients on chronic hemodialysis who had never been exposed to aluminum intoxication and who agreed to have a bone biopsy after double tetracycline labeling. The serum concentrations of PTH were measured using a two-site immunoradiometric assay for intact PTH(1-84) and region specific assays directed against the C-terminal (53-84) fragment or the midregion (44-68) of the molecule. The bone histomorphometric analysis showed that six patients had nonaluminic adynamic bone disease with low bone formation rate (BFR), eight had mild hyperparathyroidism characterized by increased bone resorption and normal BFR, nine had severe hyperparathyroidism with increased BFR, and only one had true osteomalacia with increased osteoid seam thickness. All PTH assays correlated with the various parameters of bone resorption and bone formation and were able to differentiate the histological type of bone disease only when groups of patients were considered. For classifying individual patients into severe hyperparathyroidism and adynamic bone disease groups, the intact PTH assay had the best predictive value with a sensitivity of 100% and a specificity of at least 70%. A nonaluminic adynamic bone disease was observed in more than 50% of the patients who had normal intact PTH levels (6/11). It is concluded that the intact PTH measurement is superior to C-terminal and midregion assays for the prediction of the histological type of bone disease in hemodialyzed patients and should be of considerable value to adapt their treatment in order to avoid the emergence of both severe hyperparathyroidism and adynamic bone disease. In the absence of aluminum intoxication it seems that maintaining intact PTH concentrations 1 to 1.5 times the upper limit of normal would correspond to the best bone histology.

Parathyroid hormone related protein (PTHrP) and breast cancer.

PTHrP, a newly characterized peptide is responsible for humoral hypercalcemia of malignancy in squamous cancers. It is also expressed by a variety of normal tissue and might have growth factor propriety. It is expressed by lactating breast and is frequently present in breast cancer. Although it is responsible for humoral hypercalcemia in an animal model of breast cancer its role in breast cancer hypercalcemia is still putative. The possibility that it might be one of the autocrine growth factors implicated in breast cancer cell proliferation has been suggested.

The resistance to parathyroid hormone of fibroblasts from some patients with type Ib pseudohypoparathyroidism is reversible with dexamethasone.

Skin fibroblasts from some patients with pseudohypoparathyroidism type Ib (PHP-Ib) are resistant to PTH. To characterize the defect producing PTH resistance in these cells and determine whether the abnormality is potentially reversible, we evaluated the ability of fibroblasts from patients with PHP-Ib to produce cAMP in response to PTH both before and after exposure to dexamethasone, an agent known to increase PTH responsiveness in other cell types. Before dexamethasone treatment, fibroblasts from five of eight patients with PTH-Ib produced reduced amounts of cAMP in response to PTH (but not prostaglandin E1 and forskolin) compared to that of control cells (6.3 +/- 1.0 and 37.3 +/- 6.3 pmol cAMP/100 micrograms protein, respectively). Whereas dexamethasone pretreatment had no effect on cAMP production by control or PTH-responsive PHP-Ib fibroblasts, it resulted in a dose-dependent increase in PTH-induced cAMP production by PTH-resistant fibroblasts to normal levels in four of five cases. Studies evaluating the binding of radiolabeled PTH did not permit quantification of the small number of high affinity PTH receptors present on these cells. We conclude that PTH resistance in PHP-Ib patients with PTH-resistant fibroblasts results from an abnormality in the expression of or coupling to cyclase of high affinity PTH-receptor complexes. Because it is expressed in only some tissues and is reversible, the defect could be regulatory in nature.

Optimal correction of acidosis changes progression of dialysis osteodystrophy.

To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these two subgroups patients were randomly allocated to two therapeutics groups: 10 patients (group A) were dialyzed with the conventional amount of bicarbonate (33 +/- 2 mmol/liter) in the dialysate; the rest of the patients (group B, N = 11) had 7 to 15 mmol/liter sodium bicarbonate added to the dialysate to obtain 24 mEq predialysis bicarbonate plasma levels. An effective correction of acidosis was shown in group B by a higher predialysis plasma bicarbonate level (15.6 +/- 1 group A vs. 24.0 +/- 0.6 mEq/liter group B, P less than 0.005), which was reached three months after start of the study. Compared to the prestudy bone biopsy, osteoid and osteoblastic surfaces increased in group A but not in group B on the bone biopsies performed at the end of the study. Parathormone plasma level (iPTH), measured with an antiserum which cross reacts with the 44-68 region of PTH molecule, increased during the study in group A but not in group B. This finding suggested progression of secondary hyperparathyroidism (HPT) only in group A patients. Osteocalcin plasma values increased in both groups during the 18 months of the study. Consequently the two subgroups of patients formed on the basis of BFR level were evaluated separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between histomorphometric features of bone formation and bone cell characteristics in vitro in renal osteodystrophy.

To determine whether abnormal bone cell recruitment or differentiation may be involved in the development of aplastic bone lesion in renal osteodystrophy we have compared histomorphometric parameters of bone formation and in vitro behavior of osteoblastic cells isolated from the trabecular bone surfaces in 37 dialysis patients with osteitis fibrosa, normal bone formation rate, or aplastic bone lesion. The bone cell responses to human PTH-(1-34) (20 nmol/L), as evaluated by intracellular cAMP production, and to 1,25-dihydroxyvitamin D (10 nmol/L), as assessed by osteocalcin synthesis, were not different from normal in patients with low, normal, or high bone formation rates. Osteoblastic cells isolated from patients with a high bone formation rate and markedly elevated serum iPTH and osteocalcin values had a higher than normal DNA replication in primary culture. The peak of [3H]thymidine incorporation, the maximal DNA synthesis, and the area under the growth curve were 4.4- to 6.3-fold increased in osteitis fibrosa compared to those in normal bone cells obtained from age-matched individuals. By contrast, [3H]thymidine incorporation in bone cells from aplastic patients was about 25% of normal and only 5% of the value in osteitis fibrosa. The decreased DNA replication of cultured bone cells in aplastic patients was unrelated to trabecular bone aluminum staining, but was associated with low serum immunoreactive PTH values compared to those in other groups of patients. These results show that high bone formation in uremic osteoitis fibrosa is associated with higher than normal [3H]thymidine incorporation in bone cells in vitro, whereas low bone formation in aplastic patients results from lower than normal DNA replication and suggest that the defective osteoblastic recruitment in aplastic patients may be related to factors other than aluminum, including inappropriate PTH secretion.

Cortical v trabecular bone aluminum in dialyzed patients.

Differences among measurement of cortical and trabecular bone aluminum (AI) have been observed. Furthermore, its relationship to bone histology has been variable. In order to clarify these points, we have evaluated measurements of bone AI in relation to the source of AI and bone lesion in 25 hemodialysis patients. All patients were dialyzed in the same unit since commencement of dialysis and treated by the same physician. Age of the patients ranged from 29 to 66 years; mean duration of dialysis was 6.6 +/- 3.5 years. Dialysate water has been treated by reverse osmosis since 1980. Bone biopsy was performed in all patients after double tetracycline labeling. AI was measured biochemically in cortical bone (bCAI) and histochemically in trabecular (TAI) and cortical bone (CAI). Mean serum AI (36 +/- 21 micrograms/L) and bCAI (59 +/- 44 micrograms/g) were increased. There were significant correlations between: cortical AI and (1) serum AI (r = 0.71, p less than 0.001); (2) duration of dialysis with softened water (AI content, 55 +/- 21 micrograms/L, r = 0.65, P less than 0.001) but not with total duration of dialysis; and (3) AI ingested since commencement of dialysis (r = 0.57, P less than 0.01). Trabecular AI was not correlated with any of these parameters. None of cortical AI measurements were correlated with bone formation rates (BFR), osteoblastic surfaces (ObS), and resorption surfaces (RS) determined on trabecular bone. However, trabecular AI was inversely correlated with BFR (P less than 0.01) and ObS (P less than 0.05). Serum parathyroid hormone (PTH) was positively correlated with BFR (P less than 0.001) and RS (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary hyperparathyroidism seen in rheumatology. Clinical symptoms and the relation between bone histologic signs and biological parameters]. / Hyperparathyroïdie primitive vue en rhumatologie. Signes cliniques et relations entre les signes histologiques osseux et les paramètres biologiques.

We report the clinical and biological picture of 34 primary hyperparathyroidism (PHT) cases, diagnosed in rheumatology. It concerned 25 women and 9 men, aged 61 + 11 years. The PHT was often asymptomatic (47 p. cent of cases) at the time of diagnosis. The clinical manifestations were dominated by asthenia (50 p. cent) and renal lithiasis (47 p. cent). We found a chondrocalcinosis in 29 p. cent of patients. No patient presented any bony manifestations of cystic osteitis; 7 out of 34 patients (including 6 women between 57 and 74 years) presented vertebral compression. The mean calcemia was 117 +/- 9 mg/l. There were no hypercalcemic attack. The dosage of PTH and cyclic AMP were elevated in 29 out of 32 and 28 out of 31 patients respectively. In all patients, the level of either of these two tests was increased. The chloremia/phosphoremia ratio was also extremely predictive of HBP, since it was increased, exceeding 3.3 in 33 out of 34 patients. The 25-hydroxyvitamin D levels (25 (OH) D) were normal. The levels of 1,25 (OH) 2D were markedly spread (37 +/- 16 pg/ml) and not significantly different from the reference group. Patients with lithiasis did not present a higher level of 1,25 (OH) 2D. A bone histomorphometry carried out in 15 patients showed a bone trabecular volume similar to that of the reference with the same age. The osteoclastic resorption was increased in all cases and was not correlated with the PTH level, but was significantly correlated with the level of 1,25 (OH) 2D (r = 0.79 p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma bone Gla-protein: assessment of its clinical value as an index of bone formation in hemodialyzed patients.

Plasma bone-Gla protein was measured in 27 non-selected patients on chronic hemodialysis or hemofiltration with no overt radiological bone disease. Individual values ranged from normal to 10-times the upper limit of the normal range. Plasma bone-Gla protein correlated with the histomorphometric parameters of bone turnover and bone formation and with plasma parathyroïd hormone and alkaline phosphatase. When patients were classified according to their Bone Formation Rate, plasma bone-Gla-protein allowed a better distinction between high and low bone formation rates than did alkaline phosphatase or plasma parathyroïd hormone.