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Biomedical subjects

P Brun

Publications and source records attributed to P Brun.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cyclosporine pharmacokinetics in nephrotic and kidney-transplanted children.

The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39%, blood clearance was 0.55 l.h-1.kg-1 and volume of distribution at steady-state was 2.77 l.kg-1. The absorption profile was monophasic (67%), biphasic (29%) or poor (4%). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng.ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l.h-1.kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.

Absorption↗
PubMed1994

Complete inherited deficiency of the fourth complement component in a child with systemic lupus erythematosus and his disease-free brother in a north African family.

Although null alleles of complement C4 genes (C4A*Q0 and C4B*Q0) are frequent in the normal population, the occurrence of two null alleles on the same chromosome is very rare and therefore complete C4 deficiency is exceptional. We describe a 16-year-old North African boy who presented with systemic lupus erythematosus with renal involvement and persistent undetectable classical pathway activity and C4 protein and hemolytic activity in plasma, with normal C3 levels. Similar complement abnormalities were observed in his healthy 12-year-old brother. Complete C4 deficiency was documented in the two brothers by investigation of the family and the lack of C4A and C4B bands upon phenotyping of C4. Southern blot analysis of the C4/CYP21 gene organization in the family indicated that the deficiency resulted from a deletion of the C4B/CYP21A genes associated with nonexpression of a C4A gene. The double-null haplotype was found to be associated with homozygous A2 B17 C2C BFF C4 AQ0 BQ0 DR7 HLA haplotype. Thus, similar C4 deficiencies with HLA identity may lead to different clinical presentations.

Adolescent↗
PubMed1994

SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission.

Unilateral microinjection of neurotensin in the ventral tegmental area of the rat (2.5 micrograms/0.5 microliter) produced behavioural excitation illustrated by contralateral circling. Given orally, SR 48692, a selective and potent non-peptide neurotensin receptor antagonist, significantly reduced these rotations with a triphasic dose-effect relationship. Inhibition occurred at 0.12 mg/kg; further increases in dose up to 2.5 mg/kg produced no significant antagonism, then at doses > or = 5 mg/kg, a second phase of antagonism was observed. Bilateral injection of neurotensin (0.5 microgram each side) into the nucleus accumbens antagonized the increase in locomotor activity following intraperitoneal injection of amphetamine. Given orally, SR 48692 reduced dose-dependently (0.1-1 mg/kg) these intra-accumbens neurotensin effects. Using high pressure liquid chromatography with electrochemical detection, we showed that microgram amounts of neurotensin injected into the ventral tegmental area increased dihydroxyphenylacetate/dopamine ratios in the nucleus accumbens. Using in vivo voltammetry techniques, we found that the injection of nanogram and picogram amounts of neurotensin in the ventral tegmental area stimulated dopamine efflux in the nucleus accumbens. None of these biochemical changes were affected by SR 48692 (0.1-10 mg/kg). These results indicate complex interactions between neurotensin and the mesolimbic dopamine system. More particularly, the differential ability of SR 48692 to affect neurotensin-evoked behavioural versus biochemical changes supports the concept of neurotensin receptor heterogeneity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Juvenile pityriasis rubra pilaris associated with hypogammaglobulinaemia and furunculosis.

We report a case of follicular keratosis with inflammatory changes, consistent with a diagnosis of atypical juvenile pityriasis rubra pilaris. An unusual feature was the occurrence of severe Staphylococcus aureus folliculitis and furunculosis, a phenomenon rarely encountered in pityriasis rubra pilaris and the other follicular keratoses. Standard antibiotic and antiseptic treatment for chronic S. aureus infection was ineffective. The patient was subsequently found to have hypogammaglobulinaemia, and treatment with human polyvalent immunoglobulin infusions was successful in eradicating the sepsis. It is therefore probable that the hypogammaglobulinaemia played a pathogenic role in the development of cutaneous sepsis.

Adult↗
PubMed1994

Selective disappearance of C3NeF IgG autoantibody in the plasma of a patient with membranoproliferative glomerulonephritis following renal transplantation.

The serum of patients with membranoproliferative glomerulonephritis (MPGN) often exhibits C3 nephritic factor activity (C3NeF) associated with autoantibodies directed against the C3bBb alternative complement pathway C3 convertase. In the present study, we have sequentially assessed C3NeF activity in the purified IgG fraction of the serum of a patient with MPGN type II and end-stage renal disease every month for 1 year following renal transplantation and bilateral nephrectomy. C3NeF activity in the patient's purified serum IgG decreased with time from the first month after transplantation and became undetectable after forty-five weeks. At that time, plasma levels of C3 and factor B had returned to normal values. The disappearance of C3NeF activity in patient's IgG was selective in that no change in activity of two other autoantibodies and of one antibody against a non-self antigen was observed with time, indicating that the decrease in C3NeF activity was not related to a non-specific effect of immunosuppressive therapy. Loss of C3NeF activity was not related to the generation of anti-idiotypic antibodies against C3NeF. This study documents for the first time the selective disappearance of C3NeF activity following renal transplantation and bilateral nephrectomy. The results suggest that the autoantibody represents an antigen-driven expansion of self reactive B cell clones in response to a specific disease process in the kidney of patients with MPGN.

Adult↗
PubMed1993

Differential effects of desipramine on direct- and sensory-evoked noradrenaline release in thalamic locus coeruleus terminals.

The effects of desipramine on sensory-evoked (sciatic nerve stimulation) activation of locus coeruleus neurones were investigated in vivo by using treated carbon-fibre electrodes in conjunction with either differential normal pulse voltammetry or differential pulse amperometry. Firstly, the amplitude of the sensory-evoked increase in extracellular noradrenaline, monitored in thalamic locus coeruleus terminals, was not modified by desipramine (10 mg/kg), whereas that evoked by direct activation of locus coeruleus neurones was greatly increased: +143% for dorsal noradrenergic bundle stimulation and +761% for glutamate ejection in the locus coeruleus. Secondly, desipramine administered at the same dose significantly reduced (-48%) the activation of locus coeruleus neurones (monitored at the somato-dendritic level) evoked by prolonged sciatic nerve stimulation. Our results indicate that acute treatment with desipramine does not potentiate overall noradrenergic transmission by locus coeruleus neurones during sensory stimulation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Distinct molecular origins for Denys-Drash and Frasier syndromes.

The direct involvement of the Wilm's tumor suppressor gene (WT1) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.

Base Sequence↗
PubMed1993

Is penicillin G an adequate initial treatment for aspiration pneumonia? A prospective evaluation using a protected specimen brush and quantitative cultures.

OBJECTIVE: To evaluate the bacteriology of early aspiration pneumonia using a protected specimen brush and quantitative culture techniques, and whether penicillin G is adequate as initial treatment pending culture results. PATIENTS AND METHODS: 52 patients (of which 45 required mechanical ventilation) meeting usual clinical criteria for aspiration pneumonia were prospectively included. On admission, patients were given intravenous penicillin G and a protected specimen brush was performed < or = 48 h after. RESULTS: Cultures of the brush were negative (< 10(3) CFU/ml) in 33 patients (1 had blood cultures positive with S. pneumoniae) and positive (> or = 10(3) CFU/ml) for S. pneumoniae in 2 patients. Seventeen patients had a positive culture (> or = 10(3) CFU/ml) for at least one penicillin G resistant microorganism, with a total of 20 organisms (S. aureus: 6; H. influenzae: 2; Enterobacteriaceae: 8; P. aeruginosa: 3; C. albicans: 1). In 4 of these patients, a penicillin-sensitive pathogen was also recovered in significant concentrations (S. pneumoniae: 2; Streptococcus sp.: 2). These 17 patients with a resistant pathogen did not differ from the 35 other patients with respect to need for ventilatory support and mortality rate. By contrast, they were older (61.1 +/- 21.9 vs. 42.9 +/- 18.8 years; p < 0.005) and required longer mechanical ventilation (6.1 +/- 4.6 vs. 3.5 +/- 2.7 days; p < 0.03) and hospitalization (11.2 +/- 8.8 vs. 6.7 +/- 4.7 days; p < 0.02). Of 17 patients 12 with penicillin G resistant organisms versus 0/35 without, were in-hospital patients and/or had a digestive disorder (p < 0.001). CONCLUSION: The broad range of offending organisms seen in early aspiration pneumonia precludes use of any single empiric regimen, making protected specimen brush mandatory in many patients. Nevertheless, the involvement of S.pneumoniae in a notable proportion of our patients suggests that routine penicillin prophylaxis after early aspiration (at least in most patients with community-acquired aspiration) is warranted given the potential severity of pneumococcal sepsis in such patients.

Adult↗
PubMed1993

In vivo noradrenaline release evoked in the anteroventral thalamic nucleus by locus coeruleus activation: an electrochemical study.

The anteroventral thalamic nucleus is innervated by noradrenergic terminals exclusively originating in the locus coeruleus, a densely packed cell group located in the dorsotegmental part of the pons. In urethane-anaesthetized rats, electrical stimulations of locus coeruleus axons (dorsal noradrenergic bundle; 14 Hz, 20 s) evoked a rapid increase in the signal (catechol oxidation current) measured within the anteroventral thalamic nucleus by the use of carbon fibre electrodes combined with electrochemistry. This effect was reproducible and immediately reversible. Evoked changes in this current were found to be due to oxidation of noradrenaline released from terminals. The amplitude of the evoked noradrenaline release varied non-linearly with the frequency of stimulation. We investigated the influence of locus coeruleus activation on noradrenaline release measured in the anteroventral thalamic nucleus every second by means of differential pulse amperometry: (i) chemical activation of locus coeruleus by local injection of glutamate (0.2-0.8 nmol) immediately and consistently evoked noradrenaline release in a dose-dependent manner; and (ii) peripheral stimulation of the sciatic nerve (20 s)--known to enhance the firing rate of locus coeruleus neurons-evoked a noradrenaline release similar to that produced by a stimulation of the dorsal noradrenergic bundle at 8-10 Hz. Pharmacological and kinetic characteristics of the noradrenaline release were the same for central or peripheral stimulation of locus coeruleus neurons. Our results indicate that in vivo electrochemistry, because of its sensitivity and its high space and time resolution, is well suited for studies of evoked noradrenaline release from locus coeruleus terminals. This approach allowed us to describe the characteristics of central noradrenaline release evoked by central and peripheral stimulations of short duration. In particular, we observed a very close relationship between impulse flow and evoked noradrenaline release.

Animals↗
PubMed1993

Clinical significance of borderline quantitative protected brush specimen culture results.

In patients with clinical suspicion of pneumonia, quantitative cultures of protected brushing specimens (PBS) yielding > or = 10(3) CFU/ml of at least one microorganism have been found useful for differentiating airway colonization and lung infection, especially in mechanically ventilated patients. The amount of secretions collected by protected catheter brushing is small and difficult to determine accurately. Thus, the clinical significance of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml, in the absence of active antimicrobial treatment, is unknown. The 34 consecutive results of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml in 30 patients under mechanical ventilation or weaned for < or = 4 days were prospectively studied. No patients were receiving agents active on the organism recovered. In 5 cases, the diagnosis of pneumonia was ruled out by recovery without treatment (n = 4) or negative postmortem lung cultures (n = 1). A second PBS was cultured in 29 episodes (2.7 +/- 1.8 days after the first PBS). In 12 instances (Group 1), cultures of the second PBS yielded > or = 10(3) CFU/ml of the same organism as that found in the first PBS (S. pneumoniae, 1; S. aureus, 1; H. influenzae, 1; E. coli, 1; P. aeruginosa, 4; and A. baumannii, 4), and these patients were therefore treated with appropriate antibiotics. A total of 17 patients had a negative repeat PBS culture (no growth or trivial concentrations) and were considered free of pneumonia and given no antibiotic treatment for this episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1993

Prospective evaluation of the incidence of bacteremia after protected specimen brushing in ICU patients with and without pneumonia.

To test the hypothesis that the use of protected specimen brushing (PSB) via flexible bronchoscopy does not predispose to bacteremia in ICU patients, we prospectively performed aerobic and anaerobic blood cultures immediately following bronchoscopy with PSB. A total of 123 episodes in 68 consecutive patients with suspected pneumonia were analyzed. Blood cultures were negative in 110 cases (89 percent) and positive in 13 cases (11 percent) (p < 0.001). Twelve of these 13 patients with positive blood cultures had quantitative PSB specimen cultures showing nonsignificant growth (< 10(3) CFU/ml). In nine patients, the bacteria recovered from blood cultures (coagulase-negative staphylococci or sarcina) were considered nonpathogenic according to conventional criteria. Blood cultures grew a Staphylococcus aureus in two patients with previously documented staphylococcal septicemia. In one patient with no identifiable site of infection, the blood culture yielded Enterococcus faecalis. The only patient with both a positive blood culture and PSB culture results indicating pneumonia had different organisms recovered from the two samples. Blood cultures taken after PSB in the 17 other episodes of pneumonia (PSB specimen cultures > or = 10(3) CFU/ml) were negative. At the time of brushing and blood sampling for culture, none of these patients was receiving antibiotics active on the organisms found. In conclusion, the incidence of bacteremia after PSB in ICU patients seems very low even in patients with documented pneumonia. Substantial savings would result from not performing routine blood cultures after PSB.

Aged↗
PubMed1993

[Doppler echocardiographic evaluation of mitral flow velocity and prognosis of cardiac insufficiency].

The aim of this study was to determine the role of Doppler echocardiography in establishing the prognosis of Stages to 4 cardiac failure. The echocardiographic indices of left ventricular filling were correlated with catheter data and the 2 year out come of patients. The study population included 54 patients examined prospectively in the context of an evaluation of their cardiac failure. Two years after the initial examination, 19 patients were dead or transplanted. Of the remaining 35 patients, 18 were reevaluated at 6 months. Of the echocardiographic parameters, "hyper normal" mitral flow with a high E/A ration indicated poor prognosis; when E/A > 2, the one year survival was 50% and the 2 year survival 42%. There was overlap between the groups of dead or transplanted and surviving patients only when the E/A ratio was between 2 and 3. The patients with E/A < 2 were all alive without any major events at 2 years. All patients with E/A > 3 had a poor prognosis. The E/A ratio was closely correlated with pulmonary capillary pressure levels (p < 0.001, r = 0.55) and lees closely with cardiac index (p < 0.05, r = 0.4) and radionuclide ejection fraction (p < 0.05, r = 0.28). After 6 months' vasodilator treatment with an angiotensin converting enzyme inhibitor (captopril) the E/A ratio decreased significantly from 1.85 +/- 0.78 to 1.0 0.55 (p < 0.02). A "hyper-normal" mitral flow is related to many factors, including high left ventricular filling pressures, mitral regurgitation and reduced left ventricular compliance. This appearance of mitral flow is a poor prognosis factor in severe cardiac failure.

Actuarial Analysis↗
PubMed1993

[Treatment of renal vein thromboses in the newborn].

Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis.

Clinical Trials as Topic↗