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R Lepage

Publications and source records attributed to R Lepage.

At least 19 recordsLinked to original sources
PubMed2002

Automatic P-wave analysis of patients prone to atrial fibrillation.

A method is presented for automatic analysis of the P-wave, based on lead II of a 12-lead standard ECG, in resting conditions during a routine examination for the detection of patients prone to atrial fibrillation (AF), one of the most prevalent arrhythmias. First, the P-wave was delineated, and this was achieved in two steps: the detection of the QRS complexes for ECG segmentation, using a wavelet analysis method, and a hidden Markov model to represent one beat of the signal for P-wave isolation. Then, a set of parameters to detect patients prone to AF was calculated from the P-wave. The detection efficiency was validated on an ECG database of 145 patients, including a control group of 63 people and a study group of 82 patients with documented AF. A discriminant analysis was applied, and the results obtained showed a specificity and a sensitivity between 65% and 70%.

Adult↗
PubMed2002

Origin of parathyroid hormone (PTH) fragments detected by intact-PTH assays.

BACKGROUND: Intact parathyroid hormone (I-PTH) assays react with non-(1-84)PTH, large carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. They account for up to 50% of I-PTH in renal failure and may be implicated in PTH resistance. We wanted to know if they were secreted by the parathyroid glands and generated by peripheral metabolism of PTH(1-84). METHODS: Anesthetized normal and nephrectomized (NPX) rats were injected i.v. with 1.5 microg human (h) PTH(1-84). Blood was obtained from 8 rats at 2, 4, 6, 8, 12, 24, 48 and 96 min. I-PTH (Allegro I-PTH) was measured in all samples. Pools of serum were fractionated by HPLC at each time point and the fractions assayed to quantitate hPTH(1-84) and non-(1-84)PTH. Secretion studies were performed with dispersed cells from 5 parathyroid adenomas. The serum of 10 patients with primary hyperparathyroidism and cell supernatants were fractionated by HPLC and were analyzed as described. RESULTS: hPTH(1-84) disappeared from serum biexponentially. The half-life of the first exponential was similar in normal (2.08 min) and NPX (1.94 min) rats, while that of the second was longer in NPX rats (32.4 vs 20.9 min). The residual quantity of hPTH(1-84) under the curve was greater in NPX (6964+/-2392 pmol) than in normal rats (3229+/-561 pmol; P<0.001). Non-(1-84)PTH concentration was maximal at 8 min in both groups and was higher in NPX (92.8+/-13.8 pmol/l) than in normal rats (38.8+/-7.2 pmol/l; P<0.01). The area under the curve of non-(1-84)PTH was also greater in NPX (1904+/-405 pmol) than in normal rats (664+/-168 pmol; P<0.001). All parathyroid adenomas secreted non-(1-84)PTH. It represented 21.1+/-3.9% of secreted and 32.5+/-1.3% of circulating I-PTH in primary hyperparathyroidism. CONCLUSIONS: Non-(1-84)PTH, like other C-PTH fragments, originates from both the peripheral metabolism of hPTH(1-84) and from parathyroid gland secretion. Renal failure influences its concentration by increasing the amount of substrate available and by reducing non-(1-84)PTH clearance. Its higher proportion in serum relative to cell supernatants in primary hyperparathyroidism reflects the added role of peripheral metabolism and the longer half-life of fragments.

Acute Kidney Injury↗
PubMed2001

Normal parathyroid function with decreased bone mineral density in treated celiac disease.

Decreased bone mineral density (BMD) has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH) remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7+/-3.7 years (range 1.1 to 15.9). In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH) (3.77+/-0.88 pmol/L versus 2.28+/-0.63 pmol/L, P<0.001), which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score), patients had significantly lower BMDs of the hip (-0.60+/-0.96 SDs, P<0.05) and lumbar spine (-0.76+/-1.15 SDs, P<0.05). T scores were also decreased for the hip (-1.3+/-0.9 SDs, P<0.0001) and lumbar spine (-1.4+/-1.35 SDs, P<0.0001), with two to three patients being osteoporotic (T score less than -2.5 SDs) and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs) in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not, an important determinant of the actual bone mass of patients. Normal parathyroid function in treated patients suggests a lack of previous severe secondary hyperparathyroidism and/or complete adaptation to prior changes in parathyroid function.

Absorptiometry, Photon↗
PubMed2001

Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor.

Even if the carboxyl-terminal (C-) fragments/intact (I-) PTH ratio is tightly regulated by the ionized calcium (Ca(2+)) concentration in humans and animals, in health and in disease, the physiological roles of C-PTH fragments and of the C-PTH receptor remain elusive. To explore these issues, we studied the influence of synthetic C-PTH peptides of various lengths on Ca(2+) concentration and on the calcemic response to human (h) PTH-(1-34) and hPTH-(1-84) in anesthetized thyroparathyroidectomized (TPTX) rats. We also looked at the capacity of these PTH preparations to react with the PTH/PTHrP receptor and with a receptor for the carboxyl (C)-terminal portion of PTH (C-PTH receptor) in rat osteosarcoma cells, ROS 17/2.8. The Ca(2+) concentration was reduced by 0.19 +/- 0.03 mmol/liter over 2 h in all TPTX groups. Infusion of solvent over 2 more h had no further effect on the Ca(2+) concentration (-0.01 +/- 0.01 mmol/liter), whereas infusion of hPTH-(7-84) or a fragment mixture [10% hPTH-(7-84) and 45% each of hPTH-(39-84) and hPTH-(53-84)] 10 nmol/h further decreased the Ca(2+) concentration by 0.18 +/- 0.02 (P<0.001) and 0.07+/-0.04 mmol/liter (P< 0.001), respectively. Infusion of hPTH-(1-84) or hPTH-(1-34) (1 nmol/h) increased the Ca(2+) concentration by 0.16 +/- 0.03 (P < 0.001) and 0.19 +/- 0.03 mmol/liter (P < 0.001), respectively. Adding hPTH-(7-84) (10 nmol/h) to these preparations prevented the calcemic response and maintained Ca(2+) concentrations equal to or below levels observed in TPTX animals infused with solvent alone. Adding the fragment mixture (10 nmol/h) to hPTH-(1-84) did not prevent a normal calcemic response, but partially blocked the response to hPTH-(1-34), and more than 3 nmol/h hPTH-(7-84) prevented it. Both hPTH-(1-84) and hPTH-(1-34) stimulated cAMP production in ROS 17/2.8 clonal cells, whereas hPTH-(7-84) was ineffective in this respect. Both hPTH-(1-84) and hPTH-(1-34) displaced (125)I-[Nle(8,18),Tyr(34)]hPTH-(1-34) amide from the PTH/PTHrP receptor, whereas hPTH-(7-84) had no such influence. Both hPTH-(1-84) and hPTH-(7-84) displaced (125)I-[Tyr(34)]hPTH-(19-84) from the C-PTH receptor, the former preparation being more potent on a molar basis, whereas hPTH-(1-34) had no effect. These results suggest that C-PTH fragments, particularly hPTH-(7-84), can influence the Ca(2+) concentration negatively in vivo and limit in such a way the calcemic responses to hPTH-(1-84) and hPTH-(1-34) by interacting with a receptor different from the PTH/PTHrP receptor, possibly a C-PTH receptor.

Animals↗
PubMed2000

Longitudinal study of bone density and its determinants in women in peri- or early menopause.

The evolution of bone mass across menopause as well as the factors related to bone loss were studied in 141 women already assessed 10 years ago while in premenopause. Bone density of the lumbar spine was measured by dual photon absorptiometry. Nutrient intakes, lifestyle habits, data on menopause, and hormone replacement therapy were obtained by questionnaires. Present bone density was related significantly to past and current calcium intake, current vitamin D intake, and leisure physical activity level, as well as bone density measured in premenopause. Average bone loss was related to time elapsed without estrogens, age at menopause and present age, as well as serum levels of osteocalcin and alkaline phosphatase (ALP). Bone loss was inversely related to calcium and vitamin D intakes and to serum 25-OH vitamin D (25OHD) levels. By multiple regression analyses, only bone density in premenopause, time without estrogens, weight, vitamin D intake, and serum ALP levels remained as independent predictors of present bone mass or bone loss. This study emphasizes the importance of building a good bone mass before menopause, of having adequate vitamin D intake, and of beginning estrogen replacement therapy as soon as possible to minimize bone loss in the first years of menopause.

Adult↗
PubMed2000

Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes.

Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.

Animals↗
PubMed2000

Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays.

BACKGROUND: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. METHODS: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL. min(-1). 1.73 m(-2), 12 with a GFR between 30 and 60 mL. min(-1). 1.73 m(-2), and 8 with a GFR between 5 and 30 mL. min(-1). 1.73 m(-2). We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups. RESULTS: Only patients with a GFR <30 mL. min(-1). 1.73 m(-2) and hemodialyzed patients had decreased Ca(2+) and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca(2+) (r = -0.66; P <0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvitamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL. min(-1). 1.73 m(-2), and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. CONCLUSIONS: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL. min(-1). 1.73 m(-2). Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.

Adult↗
PubMed1999

Non-invasive diagnosis of venous thromboembolism in outpatients.

BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography. METHODS: 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and Hôpital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months. FINDINGS: A normal D-dimer concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism in 286 (31%) members of the study cohort, whereas DVT by ultrasonography established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of the remaining patients. Venous thromboembolism was also deemed absent in patients with low to intermediate clinical probability of DVT and a normal venous ultrasonography (236 [26%] patients), and in patients with a low clinical probability of PE and a non-diagnostic result on lung scan (107 [12%] patients). Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of the patients, respectively. Hence, a non-invasive diagnosis was possible in 866 (94%) members of the entire cohort. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.8% (95% CI 0.9-3.1). INTERPRETATION: A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected venous thromboembolism, and appeared to be safe.

Acute Disease↗
PubMed1999

Hypocalcemia induced during major and minor abdominal surgery in humans.

Hypocalcemia has only been rarely reported during surgical procedures not involving massive blood transfusions. The frequent observation in our hospital of a low serum ionized calcium level during surgery in nonacutely ill patients prompted us to investigate the calcium-PTH axis in three groups of subjects undergoing major (hepatectomy; n = 10), moderately severe, or minor surgery under general anesthesia (colectomy; n = 7, herniorrhaphy; n = 9) compared to that in one group of minor surgery cases under epidural anesthesia (herniorrhaphy; n = 15). Serum samples were obtained before anesthesia, after anesthesia but before surgery, and 40 and 120 min after the beginning of surgery in all groups of patients and for up to 3 days in major and moderately severe cases. Significant falls (P < 0.01), always proportional to the severity of the surgical/anesthesia procedure, were observed for ionized calcium (6-20%), total calcium (8-19%), and albumin (8-23%) accompanied by increases in intact PTH (105-635%). The decrease in ionized and total calcium correlated with a decrease in albumin (P < 0.001). Phosphorus, pH, and magnesium levels remained within the normal range. Adjustment of ionized calcium for variation in albumin revealed that 50-100% of the variation in ionized calcium could be attributed to a fall in albumin resulting from fluid administration to patients before admission to the surgery ward and between the onset of anesthesia and the end of surgery (1.2-5.6 L). Albumin- and pH-independent residual ionized calcium decreases of 12.2% in the hepatectomy group, 4.6% in the group of moderately severe and minor cases under general anesthesia, and 3.7% in the control group reflected the severity of the surgical/anesthesia procedure.

Abdomen↗
PubMed1998

Functional evidence for two types of parathyroid adenoma.

OBJECTIVE: The carboxyterminal parathyroid hormone (C-PTH)/intact (I-) PTH ratio is influenced by serum calcium concentrations in man, increasing to a maximum value in hypercalcaemia and decreasing to a minimum value in hypocalcaemia. We decided to use this ratio to screen for parathyroid tumour with a normal sensitivity to calcium, symptomatic mainly through a mass effect. DESIGN AND SUBJECTS: Nineteen patients with hypercalcaemia and elevated or inappropriate PTH, were studied in the basal state and during CaCl2 and Na2EDTA infusion and compared with 26 normal individuals. They all had one parathyroid adenoma removed surgically, and two remained hypercalcaemic. RESULTS: In the basal state, the patients were hypercalcaemic (ionized calcium 1.44 +/- 0.12 vs. 1.23 +/- 0.03 mmol/l, P < 0.001) and had elevated PTH levels (I-PTH: 10.8 +/- 8.0 vs. 2.3 +/- 0.6 pmol/l, P < 0.001; C-PTH: 31.6 +/- 38.9 vs. 5.25 +/- 1.11 pmol/l, P < 0.001) when compared with normals. Their mean C-PTH/I-PTH ratio was similar to normals (2.7 +/- 1.3 vs. 2.4 +/- 0.6, NS) but, when individual values were considered, three patients had elevated values at 4.9, 5.3 and 5.8 (normal = 1.2-3.6). The regression line between basal C- and I-PTH revealed a significantly higher slope in these patients (P < 0.0001). The 16 patients with a normal basal C-PTH/I-PTH ratio had, as a group, an increased set point of I- or C-PTH stimulation by calcium and increased values of stimulated and non-suppressible I- and C-PTH, but these abnormalities were not all present in the smaller tumours (< or = 200 mg). Only three tumours in that group were larger than 1000 mg. Serum calcium concentration was related to the increased set point and non-suppressible fraction of I-PTH in these patients (r2 = 0.797). The three patients with a high basal C-PTH/I-PTH ratio had large tumours (2346, 4364 and 17,300 mg) and were more difficult to study, requiring a larger decrease in calcium concentration to achieve maximal stimulation. In the basal state, they were already expressing a non-suppressible level of I- or C-PTH and already had a maximal C-PTH/I-PTH ratio. Our data further suggest a normal set point of I- and C-PTH stimulation in the two patients who achieved sufficient hypocalcaemia and a normal set point of C-PTH/I-PTH ratio modulation in these three patients. Their hypercalcaemia was essentially related to the non-suppressible fraction of PTH. Furthermore, larger tumours were less active than smaller ones and produced less stimulated I-PTH/100 mg of tissue. CONCLUSIONS: These data indicate two types of parathyroid tumours when calcium sensitivity is considered: (1) a majority of small tumours with abnormal sensitivity to calcium, symptomatic through an abnormal set point and an increased non-suppressible fraction and (2) a smaller number of larger tumours, with normal sensitivity to calcium and an increased non-suppressible fraction, of PTH.

Adenoma↗
PubMed1998

The set point of parathyroid hormone stimulation by calcium is normal in progressive renal failure.

An increased set point of PTH stimulation by ionized calcium (Ca++) has been observed in renal failure patients with severe secondary hyperparathyroidism. The extension of this concept to all renal failure patients has remained problematic, even if it could explain elevated PTH levels in the absence of other biochemical abnormalities. We were particularly interested in seeing whether the concept could fit patients with progressive renal failure (PRF). To achieve this, we studied 26 normals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in the basal state and during parathyroid function tests. The latter two groups were studied at the end of winter and end of summer, respectively. Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)2D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinine levels. HD had significantly lower levels of Ca++ and 1,25(OH)2D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 28.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I-PTH was increased 2-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.001 vs. others). But the set point of I-PTH stimulation by Ca++ was normal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not significant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. others). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between serum Ca++ concentration and the set point value when all three populations were analyzed together (r = 0.759, n = 47, P < 0.0001). These results indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the ambient Ca++ concentration of the patients, by mechanisms yet to be elucidated. This does not suggest participation of this factor to the genesis of the secondary hyperparathyroidism of PRF.

Adult↗
PubMed1998

A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples.

We have previously shown that the Nichols assay for intact parathyroid hormone (I-PTH) reacts with a non-(1-84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates in renal failure, accounting for 40-60% of the measured immunoreactivity. We wanted to see whether this was a common event with other commercial two-site I-PTH assays. We thus compared the ability of three commercial kits [Nichols (NL), Incstar (IT), and Diagnostic System Laboratories (DSL)] to measure I-PTH in 112 renal failure patients and to detect hPTH(1-84) and non-(1-84)PTH on HPLC profiles of serum pools from uremic patients with I-PTH concentrations of 10-100 pmol/L. The behavior of synthetic hPTH(7-84), a fragment possibly related to non-(1-84)PTH was also compared with hPTH(1-84) in the three assays. The I-PTH concentrations measured with the three assays in the 112 uremic samples were highly related (r2 > or = 0.89, P < 0.0001), and the values measured with NL were, on average, 23% higher than IT. Values measured with DSL were 23% and 56% higher than IT for values less than and more than 40 pmol/L, respectively. The three assays detected two HPLC peaks on four different profiles corresponding to hPTH(1-84) and non-(1-84)PTH. This last peak represented 36 +/- 8.4% of the immunoreactivity with NL, 24 +/- 5.5% with IT, and 25 +/- 2.8% with DSL (NL vs IT or DSL: P < 0.05). These differences were confirmed by a 50% lower immunoreactivity to hPTH(7-84) compared with hPTH(1-84) for IT and DSL but not for NL. These results suggest that most of the two-site I-PTH assays would cross-react with non-(1-84)PTH material, thus explaining about one-half of the 2-2.5 x higher I-PTH concentrations reported in uremic patients without bone involvement than in subjects without uremia.

Chromatography, High Pressure Liquid↗
PubMed1997

Effect of calcium antagonists on rat liver during extended cold preservation-reperfusion.

BACKGROUND: Nisoldipine, a calcium antagonist, has been reported to improve the quality of grafted rat livers. We thus assessed the protective effect of two calcium antagonists, nisoldipine and nickel, during extended cold ischemia-reperfusion. METHODS: Rat livers were isolated and perfused before or after 24 hr of cold ischemia in University of Wisconsin solution (4 degrees C) with or without nisoldipine or nickel. Sinusoidal endothelial cell and hepatocyte functions were measured by hyaluronic acid and taurocholate elimination, respectively. RESULTS: Similar alterations in hepatocyte and sinusoidal cell functions were found in all groups after cold ischemia with or without calcium antagonists. In a second set of experiments, liver transplantation was performed in two groups of rats with livers stored under identical conditions with or without nisoldipine. Seven of 12 animals (62.5%) in both groups survived for over 10 days after 24-hr preservation in University of Wisconsin solution. Survival rates were similar in both groups. CONCLUSIONS: Calcium antagonists do not appear to have a direct protective effect on sinusoidal endothelial cell and hepatocyte functions, nor on the overall liver preservation after extended cold preservation-reperfusion.

Adenosine↗
PubMed1997

Intravenous 1,25(OH)2D therapy increases the intact parathyroid hormone secretion set point in hemodialyzed patients.

We have studied the effect of intravenous calcitriol [1,25(OH)2D] therapy (1 microgram at the end of each dialysis session) on parathyroid secretory curves of hemodialyzed patients with near-normal basal intact (< 10 pmol/l, n = 7; NNBI) or elevated basal intact (> 10 pmol/l, n = 6; EBI) parathyroid hormone (PTH; iPTH) levels. These results were compared with those obtained in matched normal individuals (N). Our main objective was to define the influence of intravenous 1,25(OH)2D therapy on the set point of iPTH stimulation in relation to the severity of secondary hyperparathyroidism. A complete parathyroid function was obtained by CaCl2 and Na2EDTA infusions in 14 N and by modification of the dialysate calcium content in 13 hemodialyzed patients. Ionized calcium (Ca2+) and iPTH were measured regularly during hypo- and hypercalcemia. Parathyroid secretory curves were derived from these data. Both groups of patients had lower basal Ca2+ (NNBI 1.16 +/- 0.05; EBI 1.10 +/- 0.03; N 1.25 +/- 0.04 mmol/l; p < 0.001) and higher basal iPTH (NNBI 6.3 +/- 2.5; EBI 49.2 +/- 39.5; N 2.5 +/- 0.8 pmol/l; p < 0.01) levels than N with more extreme values in EBI than in NNBI patients (p < 0.001). NNBI patients had stimulated iPTH levels similar to N (18.4 +/- 7.1 vs. 17.3 +/- 7.2 pmol/l), while these levels were markedly increased in EBI patients (80.7 +/- 46.0 pmol/l; p < 0.001). After 1,25(OH)2D therapy, Ca2+ increased to 1.16 +/- 0.03 mmol/l in EBI and normalized in NNBI patients (1.25 +/- 0.07 mmol/l). Stimulated iPTH decreased by 30% in NNBI (p < 0.05) and by 21% in EBI patients (NS). These two factors contributed to a decrease in basal iPTH by 52% in NNBI (p < 0.05) and by 40% in EBI (p < 0.01). The set point of iPTH stimulation was lower than in N (1.18 +/- 0.04 mmol/l) and increased with intravenous 1,25(OH)2D therapy from 1.09 +/- 0.03 to 1.16 +/- 0.05 mmol/l in NNBI (p < 0.05) and from 1.08 +/- 0.04 to 1.12 +/- 0.04 mmol/l in EBI patients (p < 0.05). The set points and changes in set point were correlated with basal Ca2+ (r = 0.56; p = 0.003) and changes in basal Ca2+ (r = 0.64; p = 0.04) observed before and during therapy. The starting position of each patient on his secretory curve before and after 1,25(OH)2D therapy was inversely related to his starting Ca2+ concentration (n = 26; r = -0.66; p = 0.0003). Taking this into account improved the relationship between Ca2+ concentration and the set point of iPTH stimulation by Ca2+ in a stepwise regression (R2 = 0.62; p = 0.0003). However, no correlation was found between set points and stimulated iPTH values. We concluded that 1,25(OH)2D therapy induced an increase in the set point of PTH stimulation in hypocalcemic hemodialyzed patients related to a similar increase in basal Ca2+ concentration. This is in part related to the starting position of each patient on his secretory curve which will affect his set point in relation to the hysteresis phenomenon in iPTH secretion. But the set point of PTH stimulation is also related to the basal ionized calcium concentration by mechanisms yet to be elucidated.

Adult↗
PubMed1996

Variability in hepatic iron concentration measurement from needle-biopsy specimens.

BACKGROUND/AIM: Quantitative measurement of hepatic iron by biochemical analysis of liver biopsy samples is required to assess hepatic iron stores accurately. Cirrhotic livers, however, contain variable amounts of fibrous tissue and the distribution of iron within the hepatic parenchyma is not always uniform. The aim of this study was to assess the variability in hepatic iron concentration measurement from needle-biopsy specimens. METHODS: The livers from eight patients with cirrhosis selected because of elevated serum ferritin were obtained at the time of liver transplantation (n = 6) or at autopsy (n = 2). Multiple needle biopsies were done, and hepatic iron concentration was measured by atomic absorption spectroscopy. The hepatic iron index was calculated as iron concentration divided by age. RESULTS: Four cases had a mean hepatic iron index above 2.0, in the range of that reported in patients with homozygous genetic hemochromatosis, whereas the other four had an hepatic iron index of less than 2.0. The intra-individual coefficient of variation for hepatic iron concentration ranged from 11.3 to 43.7%, averaging 24.9%. The coefficient of variation was smaller in biopsy samples > 4 mg dry weight than in samples < 4 mg (19.8% vs 28.6%, p < 0.05). Histological examination of surgical biopsies from these livers showed large amounts of fibrous tissue, and inhomogeneous distribution or iron in the hepatic parenchyma. CONCLUSIONS: This study demonstrates an important variability in the measurement of hepatic iron content from needle biopsy specimens in patients with severe cirrhosis.

Adult↗
PubMed1996

Accumulation of a non-(1-84) molecular form of parathyroid hormone (PTH) detected by intact PTH assay in renal failure: importance in the interpretation of PTH values.

A molecular form of PTH different from PTH-(1-84) and present in normal serum is recognized by two-site intact (I-) PTH assays; it responds to Ca2+ changes in the same way that PTH carboxyl-terminal fragments do. To evaluate the impact of this finding, we have compared basal, stimulated, and nonsuppressible I-PTH values in 14 normal subjects and 15 renal failure patients, subdivided into 8 patients with low (< 12 pmol/L; LBI) and 7 with high (> 12 pmol/L; HBI) basal I-PTH. Samples obtained under various calcemic conditions in these 3 groups were further fractionated by high performance liquid chromatography (HPLC) and assayed for I-PTH, and the various peaks observed were quantitated by planimetry. Differences among the 3 groups were reinterpreted knowing the exact composition of I-PTH. Basal I-PTH was greatly increased in HBI (mean +/- SD, 44.1 +/- 38.6 pmol/L) compared to that in normal subjects (2.5 +/- 0.8 pmol/L; P < 0.001) or LBI (6.1 +/- 2.4 pmol/L; P < 0.001); the difference was less in these last 2 groups (P < 0.01). Similar differences were observed for stimulated and nonsuppressible I-PTH, except for stimulated I-PTH, which was similar in normal and LBI subjects. Two I-PTH HPLC molecular forms accounted for I-PTH immunoreactivity in the 3 groups. In normal subjects, PTH-(1-84) accounted for 74.9 +/- 4.3%, 79.0 +/- 3.0%, and 87.2 +/- 1.0% of I-PTH in hyper-, normo-, and hypocalcemia, respectively, but only for 44.6 +/- 2.5%, 50.5 +/- 0.7%, and 63.6 +/- 0.1% in renal failure patients, with similar results in HBI and LBI. The accumulation of a non-(1-84) PTH peak accounted for the difference between normal subjects and renal failure patients. When basal, stimulated, and nonsuppressible I-PTH values were separated into their 2 components, prior differences between HBI and LBI or normal subjects remained unchanged because of very high I-PTH values in HBI, but differences between normal and LBI subjects were entirely explained by the accumulation of the non-(1-84) PTH peak [basal, 3.0 +/- 1.2 vs. 0.5 +/- 0.2 pmol/L (P < 0.001); stimulated, 6.8 +/- 2.3 vs. 2.3 +/- 1.0 pmol/L (P < 0.001); nonsuppressible, 1.3 +/- 0.7 vs. 0.2 +/- 0.08 pmol/L (P < 0.001)]; PTH-(1-84) values were similar (basal, 3.1 +/- 1.2 vs. 2.0 +/- 0.6 pmol/L; stimulated, 12.0 +/- 3.9 vs. 15.5 +/- 6.6 pmol/L; nonsuppressible, 1.1 +/- 0.6 vs. 0.52 +/- 0.22 pmol/L). Thus, a non-(1-84) PTH molecular form detected by two-site I-PTH assays accumulates in renal failure and accounts for a larger proportion of I-PTH than that in normal subjects. Levels of I-PTH 1.57 times higher than those in normocalcemic subjects are thus required in renal failure to achieve similar PTH-(1-84) concentrations. The composition of I-PTH is also identical in all hemodialyzed patients.

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PubMed1995

Screening for thyroid disease at the menopausal clinic.

The prevalence of hypothyroidism has been reported to increase with age and to attain up to 10% in older women. We wanted to verify whether routine screening for thyroid disease could be justified in a specific sub-population of aging women, those consulting for the first time at a menopausal clinic. Standard thyroid profiles (Total T4, T3 uptake, calculated free thyroxine index (FTI), and sensitive thyroid stimulating hormone (TSH)) were obtained in 500 consecutive patients seen at such a clinic over 18 months. Thyroid microsomal and thyroglobulin antibody titers were also obtained in over half of them. Twenty-three carefully selected, age-matched, peri-menopausal hospital employees served as a reference group for the TRH response test. Thirteen women (2.6%) had previously diagnosed hypothyroidism but 4 of them were found to be sub-optimally treated. Fifty other subjects (10%) had out-of-range screening TSH levels, 7 below and 43 over the assay reference range. In the former, 3 (0.6%) were found to be hyperthyroid while in the latter 8 (1.6%) were found to be overtly hypothyroid based on TSH levels over 10 mU/L and accompanying signs and symptoms. Twelve other subjects (2.4%) were found to have sub-clinical hypothyroidism based on a positive TRH response test and a significantly increased prevalence of goiter and positive antibody titers. The remaining 23 patients had a normal TRH response test, although their mean TSH level at 30-min post-TRH and the prevalence of positive antibody titers were significantly higher than those of the control group and normal subjects respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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