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Aim: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines. Methods: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGβ values ≥10 MoM. Complementary exams and outcomes were analyzed. Results: The calculated frequency was 0.05% for hCGβ ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta. Conclusion: This study establishes the frequency of hCG or hCGβ values ≥10 MoM, presents a flow chart that optimizes follow‐up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening. Key points: What's already known about this topic? High hCG or hCGβ values have been previously reported to be associated with poor prognosis, when over 2.5 multiple of the median (MoM). What does this study add? This study specifies maternal and fetal anomalies observed in patients presenting high hCG values (≥10 MoM) at Down syndrome screening in order to define clear and optimal guidelines. We calculate the frequency of this abnormal value of hCGβ, detail the outcomes, present a flow chart that optimizes follow‐up and provide clear information for patients. [ABSTRACT FROM AUTHOR]

Cirrhosis (Cir) is often associated with chronic renal failure (CRF) in Egyptian patients on regular hemodialysis (RHD). This is largely attributed to hepatosplenic schistosomiasis and concomitant Hepatitis C viral infection. As the liver has a major role in vitamin D3 activation, we designed this study to envisage the impact of Cir on renal osteodystrophy (ROD). It included 130 consecutive age- and gender-matched subjects in 4 categories. Group I: 39 patients (34 male and 5 female; mean age 48.8 years) with Cir normal renal function; group II: 37 patients (30 male and 7 female; mean age 49.0 years) with CRF and normal liver function, on RHD for a mean duration of 6 ± 3.9 years; group III: 41 patients (30 male and 11 female; mean age 50.7 years) with CRF and concomitant Cir, stable on RHD for a mean duration of 7.0 ± 4.0 years; and group IV: 16 normal volunteers (13 male and 3 female; mean age 46.3 years). The prevalence of diabetes as well as previous infection with schistosomiasis was similar in all patient groups and that of HCV infection was alike in groups I and III. In all subjects, conventional parameters of liver and renal function were tested; in addition to measurement of serum total protein, albumin, calcium, phosphate, total and bone-specific alkaline phosphatase (B-ALP), parathormone (PTH), 5-hydroxycholecalciferol (5HD), 1,25-dihydroxycholecalciferol (1,25HD), Cross Laps (CXL) as a marker of bone resorption, and aminoterminal propeptide of type I procollagen (PINP) as a measure of bone formation. Bone mineral density (BMD) was measured by either Dual Energy X-ray Absorptiometry (DEXA) or Computerized Tomography (CT). Group II patients displayed the typical CRF profile comprising hypocalcemia, hyperphosphatemia, increased total and bone-specific alkaline phosphatases, high PTH and 25HD, low 1,25HD, increased PINP as well as CXL, and generally decreased BMD. Cir (Group III) significantly (p value at least <0.5) modified this profile in several aspects: it checked hypocalcemia (mean 8.8 vs. 7.9 mg/dL in groups II and III, respectively), hyperphosphatemia (5.15 vs. 4.9 mg/dL), and the elevation of B-ALP (62 vs. 30.5 μg/L) and PTH (89 vs. 78 pg/mL). It lowered the serum level of 25HD (18.7 vs. 13.7 ng/mL), augmented the deficiency of 1,25HD (13.4 vs. 8.0 pg/mL), did not appreciably affect the increase in bone formation (PINP 77.9 vs. 75.5 ng/mL), but ameliorated its excessive resorption (CXL 21 860 vs. 30 328 pmol/L) noticed in group II. This was associated with amelioration of the dialysis-associated osteopenia (70 vs. 33.5%) and increased incidence of osteosclerosis (30 vs. 61%), as measured by bone mineral density. Our data indicate that Cir ameliorates ROD through decreased bone resorption. This is associated with better tolerance to 1,25HD deficiency, which initiates the cascade of hypocalcemia, hyperparathyroidism, and increased bone resorption in CRF. Such tolerance may reflect upregulation of vitamin D receptors as a consequence of the humoral perturbation supervening in Cir, involving IGF-1, estrogens, or other vitamin D metabolites as 24,25 HD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD) patients. Vitamin D might have beneficial effects on vascular health. The aim of this study was to determine the prevalence of vitamin D deficiency (25-hydroxyvitamin D [25D] 16.7 ng/ml (mean follow-up, 605 +/- 217 d; range, 10 to 889; P = 0.05). Multivariate adjustments (included age, gender, diabetes, arterial pressure, CKD stage, phosphate, albumin, hemoglobin, aortic calcification score and PWV) confirmed 25D level as an independent predictor of all-cause mortality., Conclusions: Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort. Low 25D levels affected mortality independently of vascular calcification and stiffness, suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored.

Background: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance., Methods: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly., Results: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated., Conclusions: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.

Accelerated bone loss occurs in the years after menopause, and is an ongoing phenomenon in elderly women. The role of cytokines in bone loss after estrogen deficiency has been shown in ovariectomized rat and mice models. In humans, the involvement of bone resorbing cytokines is now well established. In the early years after menopause, monocyte activation leads to increased cytokine production. We have previously shown that the bone resorbing activity (BRA) of peripheral blood monocyte culture supernatants from postmenopausal women is higher than in premenopausal (Pre-M) women. This increased activity was related to interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha levels. We here investigate whether monocyte activation still occurs in older women and whether this relates to bone resorption. We studied 19 healthy Pre-M, and 24 early (E-Post-M, menopause < 10 yr) and 24 late (L-Post-M, menopause > 10 yr) postmenopausal women. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma. BRA of monocyte supernatants (expressed as the ratio of monocyte supernatant over control bones supernatant) was assessed using fetal long-bone resorbing assays. Bone resorption was determined by urinary total pyridinoline excretion. BRA was significantly increased in E-Post-M and L-Post-M, compared with Pre-M subjects (1.20 +/- 0.10 and 1.15 +/- 0.20 vs. 0.73 +/- 0.10, respectively, both P < 0.05). Moreover, BRA of bones cultured with the supernatant of Pre-M was lower than BRA of control bones. BRA was significantly correlated with levels of IL-1, IL-6, and tumor necrosis factor-alpha in supernatant. Supernatant IL-1 levels were increased in E-Post-M, compared with Pre-M women (506 +/- 180 vs. 122 +/- 30, P < 0.05). Similarly, pyridinoline levels were increased in E-Post-M and L-Post-M, compared with Pre-M subjects (8.8 +/- 1 and 10.5 +/- 0.9 vs. 5.8 +/- 0.5, respectively, both P < 0.05). BRA was significantly correlated to pyridinoline levels. These data indicate the presence of monocyte activation in L-Post-M, which may be responsible for the increased bone resorption and bone loss observed in this elderly population.

The effects of arginine butyrate and tributyrylxylitol were studied comparatively in a human sarcoma cell line. Both induced important structural and functional modifications suggestive of cell differentiation, as shown by the dose-dependent increase of alkaline phosphatase activity and total protein content, at concentrations ranging from 1mM to 5 mM expressed in butyrate equivalents. hCG beta-subunit present in the culture medium increased with differentiation. Our results show that most of the differentiation changes previously reported for sodium butyrate in cancer cell lines are also produced by both drugs. Tributyrylxylitol appears to be the more potent and effective inducer of differentiation but its use is limited << in vitro >> on account of its relative toxicity at concentrations above 3 mM butyrate equivalents.

The purpose of this study is to evaluate the place of intravenous 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in the prevention of radiologically obvious hyperparathyroidism (HPT) in patients on maintenance dialysis while excluding aluminium phosphate binder and using a dialysate calcium concentration of 1.62 mmol which keeps the intradialytic calcium balance neutral. Therefore, 47 patients without subperiosteal resorption and previously treated by oral CaCO3 and if necessary Mg(OH)2 as phosphate binder while their dialysate calcium had a Ca level of 1.62 and a Mg level of 0.2 mmol/l were randomized into a control group of 24 who were maintained on the same treatment and an experimental group of 23. This group discontinued CaCO3 and received intravenous 1 alpha-OH-D3 after each dialysis at increasing doses up to 4 micrograms and increased Mg(OH)2 as their sole phosphate binder. When plasma Ca increased above 2.7 mmol/l, the dose of 1 alpha-OH-D3 was decreased. When plasma PO4 increased above 2 mmol/l, the dose of Mg(OH)2 was increased to the highest dose not inducing diarrhea, hypermagnesemia (less than 2 mmol/l) or hyperkalemia (less than 6 mmol/l). In case of persistent hyperphosphatemia, the dose of 1 alpha-OH-D3 was decreased. Since mean plasma alkaline phosphatase was normal, HPT was monitored on the plasma concentration of 1-84 PTH for which a previous histological study showed that frank osteitis fibrosa was present only when they were above 70 pg/ml, i.e. (about twice the upper limit of the normal value). Before the study, plasma PTH was below this limit in 16 patients of the CaCO3 group and in 14 patients of the 1 alpha-OH-D3 group. After 6 months, they remained below this limit in all patients except 2 of each group. Plasma PTH was initially above 70 pg/ml in 8 of the CaCO3 and did not change significantly throughout the study, 2 patients having at 6 months a PTH level below 70 pg/ml. In contrast with intravenous 1 alpha-OH-D3, all the 9 patients with initial frank HPT decreased their PTH levels after 2 months, the levels being below 70 pg/ml in 6 cases. However, because of hypercalcemia and/or of hyperphosphatemia in spite of a highest tolerable dose of Mg(OH)2, 1 alpha-OH-D3 doses had to be decreased down to 0.4 microgram per dialysis at the 6th month so that at 6 months 6 of 9 patients had their PTH levels above 70 pg/ml, a number comparable to that of patients treated with CaCO3 (6 of 8).(ABSTRACT TRUNCATED AT 400 WORDS)

Estimation of urinary excretion of a ouabain displacing factor and dopamine was carried out immediately before delivery, and 7 days and 70 to 90 days after delivery in 12 normotensive pregnant women. Simultaneous estimation of plasma 99-126 atrial natriuretic factor, plasma renin activity, and plasma aldosterone were also undertaken. The data were compared with those obtained in a group of nonpregnant normotensive women (n = 14) and a group of pregnant normotensive women in the early phase of the third trimester (n = 14). Urinary ouabain displacing factor and dopamine levels were significantly higher in the early phase of the third trimester, as compared with nonpregnant women. But immediately before delivery, ouabain displacing factor excretion had fallen below nonpregnant values and dopamine excretion had dropped to control values. Both remained low after delivery. Plasma atrial natriuretic factor was higher in pregnant women, as compared with nonpregnant controls and remained high just before delivery and 7 and 70 to 90 days after delivery. Plasma renin activity and plasma aldosterone levels were higher during pregnancy and had fallen to nonpregnant values 7 days post partum. This drop in plasma renin activity and aldosterone by 7 days post partum, in contrast with the unchanged high values of atrial natriuretic factor, may contribute to negative sodium balance after delivery. It is concluded that there is considerable discrepancy in natriuretic and antinatriuretic factors before and after delivery.