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Biomedical subjects

A Fournier

Publications and source records attributed to A Fournier.

At least 397 records · Page 22Linked to original sources

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.

Bone Diseases↗

Comparative affinities and antagonistic potencies of various human calcitonin gene-related peptide fragments on calcitonin gene-related peptide receptors in brain and periphery.

Recent data have suggested that N-truncated human calcitonin gene-related peptide (hCGRP) fragments such as hCGRP8-37 and hCGRP12-37 behave as competitive antagonists in certain bioassays. The present study was undertaken to determine which amino acid residues between positions 8 to 12 are directly involved in ensuring high affinity and antagonist properties at CGRP receptors. In brain, atrium and vas deferens membrane preparations, hCGRP8-37 and hCGRP9-37 demonstrated affinities similar to or much higher than that of the native peptide hCGRP alpha. Shorter fragments such as hCGRP 10-37 and hCGRP 11-37 possessed less than 20% of the affinity of hCGRP alpha in these various assays demonstrating the critical importance of the Thr residue in position 9 for maintenance of adequate receptor affinity. In the in vitro guinea pig left and right atria bioassays, both hCGRP8-37 and hCGRP9-37 behaved as potent and competitive antagonists (pA2:7.0-7.7) of positive chronotropic and inotropic effects induced by hCGRP alpha. hCGRP 10-37 and hCGRP 11-37 were at least 10 times less potent (pA2: 6.1-6.6). Interestingly, both hCGRP 8-37 and hCGRP9-37 were much less potent (pA2: 6.2-6.3) in blocking the effects of hCGRP alpha in the rat vas deferens whereas only slight inhibition was observed at 1.0 microM with hCGRP10-37 and no blocking activity was detected with hCGRP11-37 at a low micromolar concentration. These results are in accordance with binding data and demonstrate further the importance of residues in positions 9 (Thr) and 10 (His) to ensure potent antagonistic properties of N-truncated hCGRP fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Evaluation and prognosis of fetal arrhythmia].

From January 1986 to August 1990, a fetal arrhythmia was diagnosed in 97 pregnant women referred to our unit. Atrial or ventricular extrasystoles were the most frequent rhythm disturbance encountered (71%). They were always well tolerated and all disappeared during the perinatal period. Tachycardia was found in 16 fetuses; 6 had a supraventricular reentrant tachycardia, 6 an atrial chaotic tachycardia, 1 an ectopic atrial tachycardia and the remaining 3 an atrial flutter. A congenital heart malformation was present in 4 fetuses. The arrhythmia induced hydrops fetalis in 25% of cases. One hydropic fetus died in utero and another needed premature delivery. Bradycardia was diagnosed in 12 cases, 3 had benign atrial blocked extrasystoles, 3 others sinus bradycardia due to fetal distress and 6 atrio-ventricular block. Atrio-ventricular block was associated with congenital malformation in 4 cases (66%). All these fetuses were hydropic and died. The 2 fetuses without cardiac malformation tolerated well their bradycardia during fetal life. Fetal arrhythmia is not rare, but in most cases is benign. Sustained tachycardia requires prompt treatment, because when hydrops fetalis appears the prognosis is worse. The major prognostic factor for atrio-ventricular block is the association with a cardiac malformation.

Arrhythmias, Cardiac↗

[Comparison of calcium acetate and calcium carbonate for the control of predialysis hyperphosphatemia].

The present study was conducted to determine whether half the dose of elemental calcium given as acetate (Ca Ac) could control on medium term the predialysis plasma phosphate as well as calcium carbonate (CaCO3) while inducing less frequent hypercalcemia. This was evaluated in a cross-over study of 3 periods of 10 weeks according to the sequence Ca Ac, CaCO3, Ca Ac, in 12 compliant patients on chronic dialysis previously treated by Ca CO3. Because of poor tolerance of Ca Ac during the first period 4 patients were excluded and the results have been assessed only on the 8 patients who completed the study. For half the doses of elemental calcium (620 +/- 250 mg versus 1310 +/- 560 mg versus 710 +/- 200 mg/day) Ca acetate allowed the same control of predialytic hyperphosphatemia (1.67 +/- .34; 1.74 +/- .32; 1.75 +/- .38) with paradoxically comparable normal mean plasma calcium concentration (2.61 +/- .14; 2.56 +/- .13; 2.55 +/- .14 mmol/l). Plasma alkaline phosphatases and intact PTH concentrations remained also stable during the 3 periods. The frequency of hypercalcemia greater than 2.75 mmol/l (12; 9; 20%) and of hyperphosphatemia greater than 2 mmol/l (17; 22; 27%) were comparable with the 2 treatments. We conclude that calcium acetate controls predialytic hyperphosphatemia as efficiently as CaCO3 for half the dose of elemental calcium without however decreasing the frequency of hypercalcemia.

Acetates↗

Endothelin reduces microvascular blood flow by acting on arterioles and venules of the hamster cheek pouch.

Superfusion of the cheek pouch with 0.1-10 nM endothelin (E) produced a concentration-related reduction in the clearance of 22Na+ used as an indicator of microvascular plasma flow. The median effective concentration was about 2 nM. The time course of E action was also concentration related. Superfusion with 10 nM E for 10 min caused a greater than 80% reduction in 22Na+ clearance; the rate at which the action of E started was significantly faster than the rate at which its action ended. Recovery did not exceed 70% even though the tissue was superfused with drug-free buffer for 90 min. The E-induced reduction in 22Na+ clearance was associated with vasoconstriction, as determined by intravital microscopy. Arterioles of 4th branching order were more sensitive to E action than arterioles of 1st or 2nd order; however, the constriction lasted considerably longer in the latter vessels. E-induced venular constriction followed a pattern analogous to that of arterioles of the same category, with the exception that the finer venules responded the least. Pretreatment of the cheek pouch with 300 nM nifedipine diminished but did not abolish the 1 nM E-induced reduction in 22Na+ clearance, and the recovery of clearance upon E washout was not accelerated by nifedipine.

Animals↗

Determination of aluminum in bone in haemodialyzed patients, using inductively coupled argon plasma emission spectrometry.

We propose a new method for measuring aluminium in bone tissue, using argon plasma emission spectrophotometry. The detection limit in the bone nitric digestion liquid was 0.015 mumol/l (corresponding to 0.0075 mumol/g, i.e. 0.2 microgram/g for a tissue sample with 1.0 g wet weight). Within-run CVs were 4.66% and 1.43% for tissues containing 0.15 and 0.64 mumol/g, respectively. Other bone constituents such as calcium, phosphorus, magnesium, sodium, potassium, do not affect aluminum results. Normal values obtained in bone of subjects not suspected of aluminium intoxication were: mean +/- SD; 0.09 +/- 0.044 mumol/g (n = 24). In dialysis patients we found a mean bone aluminium content of 0.75 mumol/g for concentrations ranging between 0.16 and 3.38 mumol/g.

Aluminum↗

Frequency and prognosis of arrhythmias after operative "correction" of tetralogy of Fallot.

Two hundred twenty-four consecutive patients operated on for tetralogy of Fallot were followed from 1 to 28 years (mean 11). Mean age at surgery was 5.3 years (range 1 to 14). Postoperative right ventricular systolic pressure was 60 mm Hg in 19 of 213 patients (9%). Fourteen patients (6%) had ventricular premature complexes on surface electrocardiograms. Seventy-nine patients underwent treadmill exercise tests, and ventricular premature complexes were induced in 17 (22%). Twenty-four-hour ambulatory monitoring in 92 patients demonstrated significant ventricular arrhythmias (greater than or equal to grade 2 of the Lown classification) in 41 (45%). The frequency of ventricular arrhythmias correlated with length of follow-up and duration of cardiopulmonary bypass. No correlation was found with age at surgery, postoperative right ventricular systolic pressure and importance of conduction defects on electrocardiogram. There were no sudden or unexpected deaths during follow-up.

Adolescent↗

Influence of thromboembolism prophylaxis by low molecular weight heparin CY 216 (Fraxiparine) on several parameters of haemostasis in patients under dialysis and receiving either unfractionated heparin or CY 216.

The hemorrhagic risk of an association of the low molecular weight (LMWH), Fraxiparine injected intravenously at the dose of 7.500 AXalCU or of unfractionated heparin (UFH) injected intravenously at the usual dose used during hemodialysis (3.750 +/- 1.280 IU + 1.000 IU after 2 hours of dialysis) to the subcutaneous administration once daily of a thromboembolism preventive dose of Fraxiparine (7.500 AXalCU) was evaluated on the modification of the following hemostasis parameters: thrombin time, activated partial thromboplastin time (APTT), anti Xa activity, in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevented efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induced a significant increase of the thrombin time and of the APTT, so explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the potential hemorrhagic risk. Nevertheless the association of SC and IV Fraxiparine 7.500 AXalC u seems preferable to the association of SC Fraxiparine with UFH.

Aged↗

Expression of the avian gag-myc oncogene in Saccharomyces cerevisiae.

The gag-myc oncogenic sequence of the avian retrovirus MC29 was first inserted in a multicopy expression vector allowing its expression in Saccharomyces cerevisiae. The oncogene transcripts were detected in yeast by Northern blot hybridization and gag-myc proteins were revealed by immunoprecipitation. On solid medium, the average size of gag-myc transformant colonies was smaller than control. In liquid cultures, the gag-myc strains had a doubling time of 4.7 h compared with 3.1 h in the controls. In one of the recipient strains, and after an initial transient period of 5 days, the gag-myc transformants became physiologically indistinguishable from control. In another recipient strain, the slow-growth phenotype is permanent. Plasmid instability is increased in gag-myc transformants. When a single copy of the gag-myc gene was inserted in a yeast chromosome, no phenotype was observed, showing that slow growth is the consequence of plasmid loss.

Animals↗

Successful treatment of chaotic atrial tachycardia with oral flecainide.

Two infants with chaotic atrial tachycardia diagnosed at birth and at 11 weeks of life, were treated successfully with oral flecainide. Both patients were in heart failure at initiation of therapy. Six months and 17 months later, respectively, they have had no recurrence of chaotic atrial tachycardia, left ventricular function returned to normal and therapy was stopped in both.

Administration, Oral↗

Quantitative autoradiographic distribution of [125I]Bolton-Hunter neuropeptide Y receptor binding sites in rat brain. Comparison with [125I]peptide YY receptor sites.

The autoradiographic distribution of [125I]Bolton-Hunter neuropeptide Y receptor binding sites was quantified in rat brain. The highest level of [125I]Bolton-Hunter neuropeptide Y binding sites was seen in the hippocampus (ventral stratum radiatum, CA3 subfield: 6029 +/- 250 fmol/g tissue). The distribution of these sites was clearly laminated, being particularly concentrated in the oriens layer (dorsal CA3 subfield: 2562 +/- 147 fmol/g tissue) and stratum radiatum (dorsal CA3 subfield: 2577 +/- 95 fmol/g tissue). Lower levels of sites were seen in the pyramidal cell layer (1708 +/- 105 fmol/g tissue) and the molecular layer (1155 +/- 116 fmol/g tissue). The cortical distribution of [125I]Bolton-Hunter neuropeptide Y receptor sites was also laminated, being particularly enriched in superficial laminae (occipital cortex, layers I-II, 4038 +/- 148 fmol/g tissue; layers III-IV, 1392 +/- 97 fmol/g tissue and layers V-VI, 1522 +/- 138 fmol/g tissue). Other areas containing high amounts of sites included the anterior olfactory nuclei (ventral part, 4935 +/- 119 fmol/g tissue; lateral part, 4530 +/- 149 fmol/g tissue; dorsal part, 3378 +/- 140 fmol/g tissue and medial part, 2601 +/- 150 fmol/g tissue); anteromedial (5168 +/- 211 fmol/g tissue), medial (4611 +/- 107 fmol/g tissue) and lateral posterior thalamic nuclei (4465 +/- 189 fmol/g tissue); medial mammillary nucleus (5555 +/- 241 fmol/g tissue); medial geniculate nucleus (4747 +/- 56 fmol/g tissue); claustrum (4123 +/- 235 fmol/g tissue); posteromedial cortical amygdaloid nucleus (3524 +/- 138 fmol/g tissue), tenia tecta (2540 +/- 195 fmol/g tissue); lateral septum (1785 +/- 90 fmol/g tissue); suprachiasmatic hypothalamic nucleus (1604 +/- 115 fmol/g tissue), and substantia nigra, pars compacta (1846 +/- 142 fmol/g tissue) and pars lateralis (1750 +/- 165 fmol/g tissue). Areas moderately enriched with [125I]Bolton-Hunter neuropeptide Y binding sites included the zonal layer of the superior colliculus (1347 +/- 71 fmol/g tissue); anterior pretectal nucleus (1172 +/- 113 fmol/g tissue); ventral tegmental area (1090 +/- 97 fmol/g tissue); periventricular fibre system (1026 +/- 48 fmol/g tissue); core of nucleus accumbens (948 +/- 29 fmol/g tissue) and area postrema (799 +/- 87 fmol/g tissue). These results are discussed with regard to some of the suggested biological effects of neuropeptide Y in the central nervous system such as effects on learning, locomotion and circadian rhythms. Moreover, we also compared the distribution of [125I]Bolton-Hunter neuropeptide Y receptor sites with that of [125I]peptide YY sites in rat brain. The resolution of the autoradiographic image is better with [125I]peptide YY most likely because of higher affinity and percentage of specific labelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ventricular arrhythmias after correction of ventricular septal defects: importance of surgical approach.

To compare the prevalence of conduction disturbances and ventricular arrhythmias in cases of postoperative ventricular septal defect, 100 patients (50 with repair by right atriotomy, group 1; and 50 with repair by right ventriculotomy, group 2) underwent complete evaluation including an electrocardiogram (ECG) and 24 h ambulatory ECG monitoring. The two groups were comparable except for a shorter follow-up duration (7 +/- 3 versus 12.4 +/- 7 years) and a younger age at evaluation (12.4 +/- 5 versus 16.9 +/- 7 years) in group 1. Complete right bundle branch block was less frequent in group 1 than in group 2 (20% versus 50%, p less than 0.05) but three of the four patients with complete atrioventricular (AV) block detected on ambulatory monitoring were in group 1. Six patients had significant supraventricular arrhythmias, all well tolerated. Ambulatory monitoring revealed significant ventricular arrhythmias (modified Lown grade 2 or higher) in 39 patients, with a lower prevalence in group 1 (30% versus 48%, p = 0.05). No correlation was found between prevalence of ventricular arrhythmias and right ventricular systolic pressure, cardiopulmonary bypass duration, presence of a synthetic patch, previous pulmonary artery banding, presence of complete right bundle branch block and cardiomegaly on chest X-ray film. Prevalence of ventricular arrhythmias increased with follow-up duration, age at evaluation and age at surgery. These were always well tolerated and did not warrant treatment. Thus, right atriotomy reduces the prevalence of right bundle branch block but does not prevent late AV block. Ventricular arrhythmias are frequent after surgical closure of ventricular septal defect whatever the surgical approach and their prevalence is not statistically different from that in postoperative tetralogy of Fallot.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Structural study of the N-terminal segment of neuropeptide tyrosine.

A series of analogues of neuropeptide tyrosine (NPY) was synthesized by solid-phase peptide synthesis using BOP as a coupling reagent for the complete synthesis. A structure-activity study of the N-terminal portion of the molecule was performed with the analogues obtained by the successive replacement of the first 10 amino acids by the residue L-alanine. NPY and its analogues [Ala1-10]hNPY were tested for their potency on rat vas deferens and for their affinity to central nervous system receptors on a rat brain membrane preparation. The results suggest that the hypothetical polyproline type II helix structure of the N-terminal segment is involved in both potency and affinity. Indeed, the substitution by L-Ala of proline residues in position 2, 5, or 8 showed important losses of activity and affinity. The more important losses were observed with the replacement of Pro-5 or Pro-8. A critical loss of potency of hNPY was also observed after the substitution of the Tyr-1 residue by L-Ala, thus confirming the important role played by this residue for the full expression of the biological activity of NPY.

Alanine↗