Aortic vasoconstriction related to smooth muscle cells ET-A and ET-B receptors is not involved in hypoxia-induced sustained systemic arterial hypertension in rats.

OBJECTIVES: We report in the present study the role of endothelin (ET-1) and ET-1 receptors in the sustained hypoxia-induced systemic hypertension. METHODS: Wistar rats were randomly assigned to live continuously in hypobaric hypoxia (CH rats) or normoxia (N rats). At the end of hypoxic stress exposure (5 weeks at 450 mm Hg), measurements of mean systemic arterial pressure were done. The effects of ET-1 in the presence or not of the endothelium and/or of specific ET-A inhibitors (BQ-123) or ET-B inhibitors (BQ-788), have been investigated in an isolated model of rat thoracic aorta. Finally, plasmatic ET-1 concentrations have been determined by assay procedure. RESULTS: Following five weeks of chronic hypoxic stress, CH rats presented a significant increase of mean systemic arterial pressure (N: 129.1+/-6.8 mm Hg vs CH: 152.5+/-3.4 mm Hg; P<0.05). Despite of this hypoxia-induced hypertension, ET-1 plasmatic concentration was not different between N and CH rats. Finally, CH rats presented a reduce response to ET-1 when compared to N rats. This phenomenon seems to be associated to the ET-A vascular smooth muscle cell receptors, since difference between N and CH rats was still present in endothelium denuded aortic rings in the presence or not of the specific ET-B inhibitors (BQ-788). In addition, in the presence of the specific ET-A inhibitor (BQ-123) response to ET-1 was abolished in N and CH rats to the same extent (N:-98%; CH:-99%). CONCLUSION: This work clearly suggests that, following long term exposure to hypoxia, ET-1 and ET-1 receptors are not involved in the persistence of systemic hypertension in a rat model, and that chronic exposure to severe hypoxic stress was associated with a downregulation of the ET-A receptors response to ET-1.

Neonatal screening for cystic fibrosis in Brittany, France: assessment of 10 years' experience and impact on prenatal diagnosis.

BACKGROUND: Neonatal screening for cystic fibrosis has been a subject of debate over the past few years. This study assesses 10 years of neonatal screening in Brittany, France, and examines its impact on prenatal screening of subsequent pregnancies in couples with an affected child. METHODS: The study included all the neonates screened for cystic fibrosis in Brittany from Jan 1, 1989, to Dec 31, 1998. The screening consisted of an immunoreactive trypsinogen assay from dried blood spots, plus, from 1993, mutation analysis. Data were collected on incidence of cystic fibrosis, and genotypic and biochemical characteristics. The use of prenatal screening of subsequent pregnancies in affected families was also investigated. FINDINGS: Of the 343,756 neonates screened, 118 children with cystic fibrosis were identified, giving an incidence of one in 2913. All mutated alleles were characterised: 34 different mutations resulting in 36 genotypes were detected. The introduction of DNA analysis into the protocol greatly reduced the recall rate and increased the sensitivity of the test. The mean cost of the screening programme was US$2.32 per screened child. 39 (34%) of the families identified by neonatal screening opted for subsequent prenatal diagnosis at least once. 12 couples would have benefited from this procedure while their first child was still symptom-free. 42 healthy children were born, and 18 pregnancies were terminated (therapeutic abortion rate of 100%). INTERPRETATION: We have shown the feasibility of neonatal screening for cystic fibrosis in Brittany. Through the detection of a large range of mutations, neonatal screening provides the opportunity for more reliable prenatal diagnosis and cascade screening. The neonatal screening programme described here could provide a good model for other countries intending to initiate such a scheme.

Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with genetic hemochromatosis.

OBJECTIVE: To determine whether the osteoarticular changes associated with genetic hemochromatosis could be explained by metabolic parathyroid hormone (PTH) disorders. METHODS: The study involved 210 patients with liver iron overload syndromes. Osteoarticular changes were numerically scored as the number of damaged joints. PTH 1-84 and 44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was found in one-third of untreated patients who had no calcium or PTH 1-84 abnormalities. Serum PTH 44-68 levels correlated positively with serum ferritin levels. In multivariate analyses, the number of affected joints correlated positively with age, serum PTH 44-68 levels, and serum ferritin levels. CONCLUSION: Liver iron overload syndromes, especially genetic hemochromatosis, are associated with elevated circulating levels of PTH fragments containing the 44-68 region, which appears to play a role in osteoarticular changes. This increase seems to be a consequence of iron overload.

Eicosapentaenoic acid reduces thrombin-evoked release of endothelin-1 in cultured bovine endothelial cells.

Endothelial cells were isolated from bovine thoracic aorta and cultured. Bovine aortic endothelial cells (BAEC) were incubated with radiolabeled arachidonic acid (3H-AA) or eicosapentaenoic acid (14C-EPA) (1 microM) for 3 hr. Both fatty acids were predominantly incorporated into phosphatidylcholine (57 +/- 2% and 62 +/- 2% respectively) and slightly into phosphatidylethanolamine (11 +/- 0.5% and 12 +/- 0.6% respectively). phosphatidylinositol (26 +/- 1.5% and 10 +/- 0.5% respectively) and neutral lipids (6 +/- 0.5% and 15 +/- 1% respectively). After BAEC incubation with 3H-AA for 24 hr with or without EPA (1 microM), the release of radioactive metabolites of AA induced by thrombin (5.5 U/ml) was strongly reduced by the preliminary treatment with EPA (72 +/- 5%). After BAEC incubation with AA, EPA or vehicle (control), endothelin-1 levels were measured by RIA in the culture medium and we observed that: 1) the basal production of endothelin-1 was not modified after either AA or EPA treatment, 2) the thrombin-evoked release of endothelin-1 was significantly reduced by EPA (5.8 +/- 0.82 and 3.8 +/- 0.50 pg/microg proteins in control and EPA-treated cells, respectively); 3) by contrast, AA had no significant effect on the thrombin-evoked release of endothelin-1. In conclusion, EPA reduces strongly the endothelin-1 release but AA is ineffective. This reduction of endothelin-1 release may account partly for some of the vascular effects of EPA.

Lack of uptake, release and action of UTP at sympathetic perivascular nerve terminals in rabbit ear artery.

A possible role of uridine 5'-triphosphate (UTP) and uridine at sympathetic nerve terminals was studied in the rabbit ear artery after incubation of isolated vessels with [3H]uridine or [3H]noradrenaline. It was found that [3H]uridine was taken up by rabbit ear artery. This uptake was largely suppressed after the removal of endothelium and was inhibited by ethidium bromide and dipyridamole. Chemical denervation of the vessels with 6-hydroxydopamine did not reduce the uptake. Following pre-incubation of the isolated vessels with [3H]uridine, there was a release of radioactivity from the superfused rabbit ear artery. UTP, UDP, UMP and uridine were detected by thin layer chromatography both in the superfusate and inside the vessels. Transmural electric stimulation (30 V, 5 Hz) induced a contraction of the vessels but did not increase the release of uridine nucleotides into the superfusate. [3H]Noradrenaline was released during electric stimulation and the addition of UTP (100 microM) had no effects on this release. To conclude, this study shows that in contrast to endothelial cells, the sympathetic nerve terminals of the rabbit ear artery do not take up uridine and do not release uridine-derived nucleotides. UTP at 100 microM is also unable to modulate the evoked release of noradrenaline. These results mainly confine the role of UTP in endothelium-derived vasodilatation via P2Y2 and/or P2Y4 receptors.

Body composition and cold resistance of the neonatal pig from European (Large White) and Chinese (Meishan) breeds.

Body composition, plasma parameters and cold resistance were compared in neonatal pigs from Chinese (Meishan, Ms) and European (Large White, Lw) breeds. Newborn Ms pigs weighed less but had a higher (p less than 0.05) percentage of body dry matter and protein than the Lw pigs, whereas both breeds had similar levels of body fat and liver and muscle glycogen. Plasma concentrations of fructose and alpha-fetoprotein were lower (p less than 0.05) in the newborn Ms pigs. Cold resistance test performed in a 6-7 degrees C environment on the same piglets when aged 2 and 24 h, showed that in both breeds, cold resistance was closely dependent upon body weight and significantly improved (p less than 0.01) with age. Despite their 16% lower body weight, Ms piglets were, at both ages studied, as resistant to cold as the Lw ones. Breed had no effect on pretest concentration of plasma glucose and noradrenaline, but pretest concentrations of plasma free fatty acids (FFA) were higher (p less than 0.01) in the Ms than in Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms piglets. Breed had no significant effect on the response of plasma glucose, FFA and catecholamines during exposure to cold. At both ages of exposure, plasma concentrations of glucose and catecholamines were significantly increased. Plasma concentrations of FFA were increased (p less than 0.01) at 2 h, but at 24 h a decrease (p less than 0.01) was observed during cold exposure. Colostrum from Ms sows had greater concentration of lipids than that from Lw sows. It is suggested that the similar resistance to cold of the Ms and Lw piglets despite the lower body weight of the former is due, in part, to a greater availability of FFA as an energy source.

Does immunodeficiency in uremic patients promote dialysis-related amyloidosis?

The present study was undertaken to evaluate the immune function of 5 hemodialysis patients with dialysis-related amyloidosis as compared to 6 without, both groups having a dialytic age from 7 to 21 years, and 5 healthy controls. We investigated serum levels of immunoglobulins (IgG, IgA, IgM), made skin tests and measured peripheral lymphocyte subsets using monoclonal antibodies. 1) The absolute numbers of T3, T4 and T8 cells were significantly lower in hemodialysis patients than controls and T3, T4 cells were lower in patients with amyloidosis than in those without: T3 (m +/- SD/microliter), 387 +/- 253 vs 744 +/- 207 (p = 0.03); T4, 262 +/- 115 vs 589 +/- 297 (p = 0.04). 2) Serum levels of IgG and IgM were significantly lower in patients with amyloidosis than in the others: IgG (m +/- SD, g/l), 10.2 +/- 1.4 vs 15.4 +/- 3.2 (p less than 0.001); IgM, 0.65 +/- 0.28 vs 1.65 +/- 0.37 (p less than 0.001). 3) Delayed hypersensitivity studied by skin tests showed less than 3 positive antigens in 4/5 patients with amyloidosis against 1/6 patients without. These data suggest there is a marked defect of T-cell help in uremic patients with dialysis-related amyloidosis.

Long-term variations of serum beta 2-microglobulin levels in hemodialysed uremics according to permeability and bioincompatibility of dialysis membranes.

Hemodialysis (HD) amyloidosis is due to beta 2-microglobulin (beta 2M) storage, the importance of which could vary with the permeability of dialysis membranes. We studied long-term variations of beta 2M in 52 patients who had been dialyzed over 1.5-20 years (mean +/- SD = 7.5 +/- 5.2), 3 X 4 h weekly. Serum samples had been stored at 30 degrees C and RIAs were done in one run with the same kits (Immunotech). At least 2 assays were done for each patient in samples collected 1-9.5 years apart. Mean beta 2M concentration in 26 ESRF patients was 31 +/- 18 mg/l. According to duration of HD and membranes used, Cuprophan (CUP) versus polyacrylonitrile (AN69), mean concentrations of beta 2M were (mg/l +/- SD): at 6 months, 55 +/- 36 vs. 54 +/- 20 (n.s.); 2 years, 55 +/- 24 vs. 61 +/- 23 (n.s.); 4 years, 79 +/- 18 vs. 64 +/- 19 (n.s.); 6 years, 69 +/- 17 vs. 55 +/- 17 (n.s.); 8 years, 76 +/- 18 vs. 54 +/- 12 (less than 0.01); 10 years, 77 +/- 17 vs. 54 +/- 14 (less than 0.02). The effect of changing membranes was also studied: CUP-AN69 (69 +/- 28 months), 79 +/- 21 vs. 54 +/- 14 (less than 0.01). Serum beta 2M (1) increased rapidly after the beginning of HD; (2) reached a plateau after 2 years in patients treated with AN69 and 4 years with CUP; (3) were significantly lower after 8 years with AN69 than with CUP, and (4) decreased significantly after changing CUP for AN69.(ABSTRACT TRUNCATED AT 250 WORDS)

[Abnormalities of the central nervous system. Results of 3 years of genetic counseling at the University Hospital of Rennes: 192 cases]. / Les anomalies du système nerveux central. Bilan de trois années de la Consultation de Génétique du C.H.U. de Rennes: 192 dossiers.

The authors present their view of screening for central nervous system malformations in Brittany, having studied 192 case histories of subjects seen in the three years of genetic counselling in Rennes. Ultrasound usually manages to demonstrate anencephaly but all too often it fails to demonstrate spina bifida. Furthermore serum or amniotic fluid alphafetoprotein levels are often poorly interpreted. Microcephaly and encephaloceles occur rarely. The ultrasound diagnosis of the latter is easy whereas it is more difficult to diagnose microcephaly. The authors point out that there are familial forms of hydrocephaly and of holoprosencephaly which are not all that rare and fairly easy to diagnose so long as one remembers this very serious abnormality.

[Normocalcemic hyperparathormonemia and articular chondrocalcinosis. Study of 69 patients compared to 57 controls]. / Hyperparathormonémie normocalcémique et chrondrocalcinose articulaire. Etude de 69 patients comparés à 57 sujets témoins.

The level of parathyroid hormone was measured by heterologue C terminal radio-immunological assay in 69 patients with clinical or radiological manifestations of the type seen in primary articular chondrocalcinosis. They were divided into three groups: P1 with undetermined clinical arthropathies; P2 with sub-chondral and arthosic arthropathies; P3 with radiologically definite chondrocalcinosis. They were compared with 57 control subjects broken up into four groups: T1 with chronic rheumatic arthritis, T2 with low back pain, T3 with primary hyperparathyroidism due to adenoma, and T4 with secondary hyperparathyroidism with renal insufficiency. A form of normocalcemic hyperparathormonaemia was demonstrated in more than one out of two patients in group P1 (15/29). It was seen in three-quarters of the cases in group P2 (12/16). And it was seen in more than a quarter of the cases in group P3 (7/24). This hyperparathormonaemia was statistically significant only in groups P1 and P2 compared to the normals in groups T1 and T2. The results we obtained in this study seem to be in complete concordance with those we obtained earlier in idiopathic hemochromatosis. This hyperparathormonaemia seems to regress with age and is often only discovered when the characteristic articular lesions have appeared. The discovery of normocalcemic hyperparathormonaemia several years before the appearance of the radiological signs of the disease would appear to be an important argument in favour of the diagnosis of early articular chondrocalcinosis. The existence of raised parathyroid hormone in primary articular chondrocalcinosis as well as in idiopathic hemachromatosis is special etiopathogenic interest even if there remain numerous questions concerning its origin and mode of action.

[Value of serum myoglobin in acute myocardial infarction. Kinetic study]. / Intérêt de la myoglobine sérique dans l'infarctus du myocarde aigu. Etude cinétique.

The rise in serum myoglobin (MGB), total CPK (CKT) and its MB isoenzyme (CK - MB) was studied and compared over the first three days of acute myocardial infarction (AMI) and correlations were sought between the peak values of these three parameters and haemodynamic and biological indices of left ventricular function. Blood was taken from MGB (radio immunological technique), CKT and CK - MB (spectrophotometry) estimation every 2 hours for 24 hours and then every 6 hours up to the 72nd hour in 36 patients with AMI less than 12 hours old. On admission, this protocol was completed by a haemodynamic study (right heart pressures, systemic blood pressure, cardiac output measurement by thermodilution), arterial gases and ECG recordings. The average delays before the pathological rise, the maximal peak value and the return to normal were significantly shorter (p less than 0.001) for MGB (2, 6 and 25 hours) than for CK - MB (5,16 and 34 hours) or CKT (5,21 and 57 hours). The sensitivity of the diagnosis of myocardial infarction was not significantly higher with MGB than CKT or CK - MB either in the whole group (sensitivity of 91.6 p. 100 for MGB and 86.1 p. 100 for CKT and CK - MB) or in a subgroup of ten patients without transmural infarction (70 p. 100 for MGB compared with 60 p. 100 for CKT and CK - MB). A significant correlation was found between the peak values of MGB (p less than 0.02) and CK- MB (p less than 0.02) and the indices of left ventricular function (PCP, PAO2 and LVSWI). This was not observed with CKT. In conclusion, apart form technical problems which remain unresolved time-consuming investigation), serum MGB gives a much earlier and as sensitive a biochemical diagnosis of AMI as CKT and CK - MB. MGB and CK - MB are much better prognostic indicators than CKT as judged by the indices of left ventricular function. Finally, MGB estimation should be of particular value in the diagnosis of secondary extension of infarction.

[Study of the valuations of serum muscular enzymes and myoglobin after maximal exercise test and during the next 24 hours (author's transl)]. / Etude des variations des taux seriques des enzymes musculaires et de la myoglobine après épreuve d' effort maximale et au cours des 24 heures suivantes.

Twenty-eight male subjects underwent a maximal exercise test on an ergometric bicycle, 13 untrained and 15 trained subjects. At rest and after this maximal exercise, indicated by the increase of the serum lactate and pyruvate acids, venous blood samples were taken to study the release of muscular enzymes (SGOT, SGPT, LDH, alpha HBDH, CPK, CPK MB) and myoglobin in the next 24 h (3 min, 30 min, 8 h and 24 h after the end of this test). The statistic analysis of the results shows significant increases in comparison with the values at rest, according to the enzymes and the groups of subjects, especially for CPK, SGOT, SGPT for which the results are homogeneous with a peak at the 3rd min and the 8th h in the three groups and for HBD and LDH in the groups of trained subjects. However these values remain most often within the normal limits. These results are compared with those of previous works on the same subjects.

[Study on myoglobinemia and its development during myocardial infarction (author's transl)]. / Etude de la myoglobinemie et de son évolution au cours de l'infarctus du myocarde.

Thirty six patients suffering from myocardial infarction were investigated by assay of their serum myoglobin, total creatine kinase and creatine kinase isoenzyme MB activities. Determination of serum myoblobin presents, with regard to creatine kinase MG, two major advantages: a very early increase after the onset of the pain (about three hours later) and a very quick clearance, allowing the diagnosis of a second episode of necrosis after about one day.

[Measurement of inflammatory activity in chronic rheumatism by blood pretein levels]. / Mesure de l'activité des rhumatismes inflammatoires chroniques par les protéines sériques.

Seventy six patients with chronic inflammatory rheumatism were treated with various non-steroid anti-inflammatory drugs for 5 to 7 days. The average variations of several serum proteins were studied. The variation of haptoglobin remained nil. Those of other serum proteins remained negative and significantly different from zero, distributed from the greatest to the smallest value of the degree of statistical significance as follow : ceruloplasmin (p < 0.0001), orosomucoide (p < 0.02), fibrinogen (p < 0.02) alpha-2-macroglobulin (p < 0.04) and alpha-1-antitrypsin (p < 0.05). The study of the partial results showed the variability of the degree of significance of the serum proteins in relation to the non-steroid anti-inflammatory drugs. The practical interest of these serum protein seemed low to measure in the short term, the efficacy of non-steroid anti-inflammatory drugs. Their interest in long term studies remains to be demonstrated compared with that of the measurement of the sedimentation rate by the technic of the sigma E.S.R.

[Amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea (author's transl)]. / Alpha 1-foetoprotéine dans le liquide amniotique à la 17e semaine d'aménorrhée gravidique. Comparaison des résultats obtenus par électroimmunodiffusion et radioimmunologie.

The amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea was tested by electroimmunodiffusion and radioimmunology. The results show a very good correlation between both methods. We can see from this study the possibility for any laboratory to test alpha 1-foetoprotein in amniotic fluid of patients with high risk pregnancies, as the beginning of pregnancy when amniotic punction is necessary without using radioimmunology.

[Inherited and familial bisalbuminemia. Acquired transient bisalbuminemia (author's transl)]. / Bisalbuminémie héréditaire et familiale. Bisalbuminémie acquise et transitoire

The present study is a survey of the different types of bisalbuminemia. In the inherited and familial form, the anomaly is fortuitously discovered and not associated with disease. The abnormal albumin fraction only differs from the normal one in a slight alteration in the aminoacid sequence, responsible for increased ("fast type") or decreased ("slow type") electrophoretic mobility. The anomaly is genetically determined and is transmitted as an autosomal codominant character. The condition is relatively rare, but has been observed in most parts of the world, with some higher incidence in many American Indian tribes. In the acquired transient biaslbuminemia, the abnormal component of the albumin is always of the fast type and occurs in patients either receiving large amounts of beta-lactamine type antibiotics, or suffering from pancreas diseases.

[Reduction of the effects of indomethacin by aspirin. Value of measurement of the articular index and sigma ESR]. / Réduction de l'activité de l'indométacine par l'aspirine. Intérêt des mesures de l'indice articulaire et de la Sigma VS

Two groups, A and B, were selected at random amongst a total of 31 patients suffering from chronic inflammatory rheumatic disorders. The patients in group A (n = 16) received succesively: Placebo (2d), Indomethacin (5d). Indomethacin + aspirin (5d). The order of the 5 day treatment periods was reversed for the patients in group b (n = 15). The daily dose of indomethacin was 150 mg. That of aspirin was 1500 mg. Four parameters were measured at the end of each period of treatment: total serum indomethacin, articular index (Ritchie), ESR (Westergren) and the sigma ESR - a new technique for the measurement of sedimentation rate. No conclusions could be drawn from the analysis of variations in ESR. Concordant and statistically significnat variations in articular index and the sigma ESR showed a reduction in the activity of indomethacin under the influence of aspirin. The inhibitory effect of aspirin. The inhibitory effect of aspirin continues after the drug stopped. This reduction in indomethacin activity is not related to a decrease in serum concentrations of the medication which are not significantly altered when aspirin is taken.