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Biomedical subjects

L Rousseau

Publications and source records attributed to L Rousseau.

At least 19 recordsLinked to original sources
PubMed2003

Breathing frequency and use of expiratory muscles do influence the dynamic positive end-expiratory pressure.

End-expiratory air trapping due to obstructive airway disease can be estimated through the measurement of intrinsic positive end-expiratory pressure PEEPi. The influence of breathing-frequency and use of expiratory muscles on PEEPi were measured in 10 normal and 10 chronic bronchitic patients (COPD). Insignificant control values of PEEPi increased to measurable values at high breathing rate in normal subjects. Control values were higher in COPD patients and increased at fast breathing rate. When corrected for the use of expiratory muscles according to simultaneous gastric pressure drop, PEEPi decreased in COPD, but still increased at high rate. We conclude that modifying the respiratory rate can increase PEEPi values independently of the severity of airway obstruction and the use of expiratory muscles. Before estimating the pathological value of a PEEPi measurement or evaluating the effects of a treatment, we always need to know the simultaneous breathing frequency.

Adult↗
PubMed2002

Does inspiratory behaviour affect the efficiency of non-invasive ventilation in COPD patients?

Non-invasive ventilation (NIV) is more and more used. Some failures of the technique have been reported, and efforts are needed to understand them. Collaboration (inspiratory behaviour) of the patient during NIV could play a role in the success of this technique. We have studied the influence of this one on the efficiency of NIV. While ventilating 10 stable chronic obstructive pulmonary disease patients with a nasal pressure support ventilation (PSV), we measured their flow and volume with a pneumotachograph and oesophageal and gastric pressures during three different respiratory voluntary behaviours: relaxed inspiration, active inspiratory effort and resisted inspiration. We showed that when compared with the relaxed inspiration: (a) Active inspiratory effort increases slightly minute ventilation from 14.8 +/- 4.7 to 15.41 +/- 4.19 during PSV 10/0 without change of breathing frequency but with an important increase of inspiratory work (W(OB)) from 14.47 +/- 9.43 to 28.55 +/- 25.35 J/min (P=0.008). PEEPi increases with active behaviour during PSV but not during BiPAP. (b) A resisted inspiration decreases inspiratory work (to 7.53 +/- 8.6 J/min) at the price of a decrease of the minute ventilation to 11.47 +/- 4.20 l/min (P=0.06). Results of ventilation, PEEPi and work parameters were identical during the bilevel pressure support (15/5 cm H2O). The aims of NIV being to increase ventilation and unload the inspiratory muscles, our results suggest that during NIV, a relaxed spontaneous breathing is preferable. These differences between the inspiratory behaviours could affect the expected benefits of PSV in acutely ill patients.

Analysis of Variance↗
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

A developmental study of the affective value of tempo and mode in music.

Do children use the same properties as adults in determining whether music sounds happy or sad? We addressed this question with a set of 32 excerpts (16 happy and 16 sad) taken from pre-existing music. The tempo (i.e. the number of beats per minute) and the mode (i.e. the specific subset of pitches used to write a given musical excerpt) of these excerpts were modified independently and jointly in order to measure their effects on happy-sad judgments. Adults and children from 3 to 8 years old were required to judge whether the excerpts were happy or sad. The results show that as adults, 6--8-year-old children are affected by mode and tempo manipulations. In contrast, 5-year-olds' responses are only affected by a change of tempo. The youngest children (3--4-year-olds) failed to distinguish the happy from the sad tone of the music above chance. The results indicate that tempo is mastered earlier than mode to infer the emotional tone conveyed by music.

Adult↗
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

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↗
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↗