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Biomedical subjects

P Landais

Publications and source records attributed to P Landais.

At least 91 records · Page 5Linked to original sources

Metabolic patterns associated with non-specific magnetic resonance imaging abnormalities in temporal lobe epilepsy.

We investigated the cerebral metabolic patterns associated with non-specific hyperintense T2-weighted image on Magnetic Resonance Imaging (MRI) in Temporal Lobe Epilepsy (TLE). Nineteen patients suffering from TLE with a normal CT scan underwent Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose; 8 had hyperintense T2-weighted image on MRI in the epileptogenic temporal lobe and 11 had a normal MRI. Interictally, PET exhibited focal hypometabolism in all the patients with hyperintense T2-weighted image and in 8 of the 11 whose MRI was normal. The hypometabolic area was significantly more extensive in patients with hyperintense T2-weighted image in whom it always encompasses the site of the MRI abnormality. Moreover, these patients had higher metabolic asymmetry index in the temporal and parietal lobes than patients with a normal MRI. One patient with mesial temporal hyperintense T2-weighted image underwent an ictal PET, which showed that the focal hypermetabolism fitted remarkably with the site and size of the abnormal MR signal. Thus, non-specific hyperintense T2-weighted images are associated with particular interictal and ictal metabolic patterns which might suggest that these MRI abnormalities reflect an epileptogenic lesion.

Adolescent↗

Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release.

Triggering of the CD3 molecule by in vivo injection of the hamster anti-murine CD3 monoclonal antibody 145-2C11 in adult BALB/c mice leads to massive although transient T cell activation. High levels of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, IL-3 and IL-6 are released into the circulation 1 to 8 h after a single 10 micrograms 145-2C11 i.v. injection. This release induces an impressive self-limited physical reaction associating hypothermia, hypomotility (as assessed by actimetry), diarrhoea, piloerection and even death when high doses (a single dose of greater than 100 micrograms/mouse injection) are administered. In vivo injection of 145-2C11 to other selected mouse strains, namely NZW, CBA/J and C3H/HeJ, induced both different cytokine release patterns and sickness. 145-2C11 induced significant release of TNF and IL-2 in all four strains. At variance, IFN-gamma was only detected in BALB/c mice sera which, in terms of physical reaction (hypothermia and hypomotility) were the most affected. Higher and long-lasting circulating IL-3/GM-CSF levels were present in CBA/J sera, correlating with a later recovery. These results underline heterogeneity in the in vivo cell activation pattern among different mouse strains, when triggering T lymphocytes via the CD3/Ti molecule as compared to exclusive targeting of monocyte/macrophages by means of lipopolysaccharide.

Animals↗

Establishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients: a randomized prospective study.

The present prospective study was conducted in order to establish the relationship between complement activation and stimulation of phagocyte oxidative metabolism observed in long-term hemodialysis (HD) patients during the early phase of dialysis with cellulosic membranes. Two groups of 10 randomized (HD) patients treated with cellulosic (Cuprophan, CUP) or synthetic polyacrilonitrile (PAN AN-69) membranes were studied. Leukocyte counts, C3a antigen plasma concentration and whole blood basal and stimulated chemiluminescence (CL) production were determined in blood samples drawn from the fistula before dialysis (T0) and from both the afferent and efferent lines of the dialyser at 15 min (T15) and at the end (Tend) of the dialysis session. This study confirms that, coincident with the nadir of leukopenia observed at T15, dialysis with CUP but not PAN membranes induces a marked rise in C3a antigen levels and profound alterations in whole blood CL production consisting of a dramatic increase in basal CL and a significant loss in CL response capacity to stimulating agents. It further demonstrates that a direct relationship exists between the variations in C3a antigen plasma levels and whole blood CL production observed in the CUP group of patients from T0 to T15 (delta 15) of dialysis. This relationship is characterized by a positive correlation between delta 15 C3a and delta 15 basal CL levels in afferent and efferent lines, and a negative correlation between delta 15 C3a and delta 15 CL response capacity values in the efferent but not afferent line. In contrast, no significant correlation with the type of dialysis membrane could be demonstrated between the variations in polymorphonuclear neutrophil counts and C3a antigen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

Intravenous immunoglobulin therapy for prevention of infection in high-risk premature infants: report of a multicenter, double-blind study.

The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed.

Cross Infection↗

Comparison of different types of cardioplegia and reperfusion on myocardial metabolism and free radical activity.

Current techniques of myocardial protection during global ischemia include hypothermia, cardioplegic arrest and controlled reperfusion. To compare different types of cardioplegia and reperfusion techniques we measured the levels of adenine nucleotides and malondialdehyde (MDA, as free radical activity) in 33 patients undergoing heart surgery. The patients were randomized in three groups according to the characteristics of cardioplegia and reperfusion: cold blood cardioplegia with unmodified blood reperfusion (control group, 11 patients), crystalloid cardioplegia and reperfusion (Hôpital Lariboisière protocol, 11 patients) and crystalloid cardioplegia with allopurinol enriched blood reperfusion (Hôpital Broussais protocol, 11 patients). Myocardial biopsy specimens were obtained before cardioplegic arrest (preischemic values), at the end of ischemia and after 30 minutes of reperfusion. Biopsy specimens were analyzed by high performance liquid chromatography for levels of adenine nucleotides and MDA. In the three groups, the preischemic values of adenine nucleotides and MDA were not significantly different. For AMP and ADP concentrations neither treatment nor biopsy-time effects appeared. ATP concentration decreased significantly with biopsy-time without specific treatment effect. For MDA concentration neither treatment nor biopsy-time effects were observed. This study suggests that there is no statistically significant difference between any of the three cardioplegia and reperfusion techniques for either ATP or MDA; the three reperfusion techniques limit the free radical activity but do not prevent the fall in high energy phosphates.

Adenine Nucleotides↗

European experience of bone-marrow transplantation for severe combined immunodeficiency.

The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.

Actuarial Analysis↗

Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation.

In vivo injection of the hamster anti-murine CD3 monoclonal antibody 145 2C11 into BALB/c mice induces a massive systemic release of several cytokines. Very high circulating levels of tumor necrosis factor are detected both by enzyme-linked immunosorbent assay and L-929 bioassay 90 min following a single injection of 10 micrograms/mouse 145 2C11. Peak circulating levels of exclusively T cell-derived products such as interferon-gamma, interleukin 2 and interleukin 3 are also detected 90 min to 8 h post-injection. Importantly, this cytokine release is transient since none of these cytokines are still present 12 to 24 h post-injection. In parallel to cytokine release, 145 2C11-treated mice (10 micrograms/mouse) exhibit somnolence, hypomotility (quantified by actimetry), hypothermia, diarrhea and piloerection. At this dosage, the physical reaction is not lethal and reverses in all mice by 48 h post-injection. Severe but again reversible anatomopathological changes are also observed: massive cellular depletion, necrosis and edema of lymphoid organs, leakage syndrome and inflammatory cell infiltrates of the lung, cell vacuolization, necrosis and vascular congestion of the liver. All these data are similar to the clinical and immunological manifestations of the OKT3-induced reaction in patients and, thus, provide an invaluable experimental tool to study its mechanisms and explore its prevention.

Animals↗

Adverse effects of sucrose-rich diets on uraemic rats.

The nature of carbohydrate may affect the tolerance and progression of uraemia. The effects of three diets differing only in their carbohydrate source: namely corn starch (C), glucose (G) or sucrose (S) were examined. Study 1 examined the effects of the three carbohydrate diets on unilaterally nephrectomised control rats and severely uraemic rats. The three carbohydrates produced similar nutritional effects in uninephrectomised rats, whereas sucrose rapidly induced anorexia, stunting and slightly accelerated renal damage in uraemia. Study 2 examined the long-term effects of the three carbohydrates in moderate uraemia under conditions of high and identical carbohydrate intakes. Hyperphagic Zucker uraemic rats (F rats) received a daily allotment of each diet plus pure carbohydrate. Lean uraemic rats (L rats) received the same dietary allotment without the carbohydrate supplement. The F rats fed sucrose showed greater morbidity and mortality but little renal deterioration. Their plasma triglycerides increased dramatically. The L rats fed sucrose had the greatest urinary protein, the least creatinine clearance and the most severe renal damage. Thus, sucrose-rich but not glucose-rich diets have two adverse effects in uraemia: a deterioration in nutritional status, perhaps related to abnormal fructose utilisation, and a long-term effect on the kidney, resulting in accelerated renal deterioration.

Animals↗

Reduction of morbidity and cytokine release in anti-CD3 MoAb-treated mice by corticosteroids.

In keeping with the in vitro mitogenic properties of anti-CD3 MoAbs, the first injections of anti-CD3 are invariably responsible for an in vivo cellular activation. This activation induces a massive cytokine release in the circulation (TNF, IFN gamma, IL-2, IL-6, and IL-3). Paralleling this release, a severe clinical reaction occurs in OKT3-treated patients and in 145 2C11-treated mice. Corticosteroids both in vitro and in vivo inhibit the production of several cytokines involved in the anti-CD3 reaction. A single 1 mg hydrocortisone dose was administered to 145 2C11-treated mice according to different kinetics schedules. When given 1 hr prior to the anti-CD3 MoAb, hydrocortisone exerted a beneficial effect on the mouse physical reaction. Hypothermia was totally abrogated at the 4-hr time point. Diarrhea decreased by 50%. Hypomotility improved although not significantly. This improvement correlated with a major modification in the anti-CD3 pattern of cytokine release. At the 90-min blood withdrawal time point cytokine serum levels showed a 100% decrease for IFN gamma, an 88% decrease for IL-6, and 85% decrease for IL-2, and a 75% decrease for TNF. At 4 hr IL-2 serum levels were diminished by 65%; IL-6, IL-3, and IFN gamma serum levels were comparable to controls; and, interestingly, TNF was still detected, whereas it has already disappeared when 145 2C11 was administered alone. Importantly, when given more than 1 hr prior to anti-CD3 injection, corticosteroids were ineffective. To conclude, high doses of corticosteroids must be given with a precise kinetics--i.e. 1 hr prior to anti-CD3 MoAb--to achieve their maximal beneficial effect in the prevention of the anti-CD3 reaction.

Adrenal Cortex Hormones↗

Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin.

Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intrauterine versus postnatal repair of created pulmonary artery stenosis in the lamb. Morphologic comparison.

Experimental lamb models were used for intrauterine creation of pulmonary artery stenosis and later intrauterine repair or postnatal repair. Intrauterine creation of pulmonary artery stenosis was performed in 23 fetal lambs at 90 +/- 1 days of gestation. Eight lambs underwent intrauterine repair of pulmonary artery stenosis at 135 +/- 1 days of gestation and were studied 110 +/- 13 days after repair. Seven lambs underwent postnatal repair at 57 +/- 9 days after birth and were studied 162 +/- 32 days after repair. Eight fetal lambs with unrepaired pulmonary artery stenosis were studied 89 +/- 18 days after birth. All study lambs were compared with normal control lambs. The systolic right ventricular pressure was significantly higher after unrepaired stenosis (78.6 +/- 6.8 mm Hg) than in other lambs, but there was no statistically significant difference after intrauterine repair (23.3 +/- 2.9 mm Hg), postnatal repair (25.9 +/- 3.4 mm Hg), and normal lambs (21.6 +/- 1.1 mm Hg). The systolic pulmonary artery pressure was also not statistically different in these three groups. The weight measurements were age-adjusted for comparison of postnatal and intrauterine repair with normal lambs. The adjusted heart weights were similar in the three groups. The comparison of the adjusted heart weight/adjusted body weight ratio (10(-3) showed a significantly higher ratio in postnatal repair (7.4 +/- 0.1) than in intrauterine repair (6.1 +/- 0.1). The adjusted right ventricular weight/adjusted left ventricular weight ratio was significantly higher in the postnatal repair group (0.71 +/- 0.01) than in both the intrauterine repair group (0.59 +/- 0.01) and normal lambs (0.59 +/- 0.01). The transverse myocyte diameter was not statistically different in all groups of animals and there were no ultrastructural changes even when the pulmonary stenosis was unrepaired. We conclude that intrauterine repair was more satisfactory than postnatal repair in terms of age-adjusted heart weight results, but we did not find any advantages of intrauterine repair in terms of histologic and ultrastructural changes.

Animals↗

[Long term course of idiopathic extramembranous glomerulonephritis. Study of predictive factors of terminal renal insufficiency in 82 untreated patients].

In a retrospective study of 82 adults with idiopathic membranous nephropathy, we have studied the predictive factors of renal death. Thirty one patients developed renal failure, sixteen of them progressed to end-stage renal failure (ESRF) (13 males and 3 females). Nine patients developed ESRF in the first 5 years following the renal biopsy. The males and the patients with a nephrotic syndrome have a high risk of ESRF. The age is not a predictive factor of poor outcome. Hypertension seems to be more frequent in patients who developed early but slowly progressive renal failure. Extensive renal interstitial lesions are indicative of poor renal prognosis.

Adult↗

Home parenteral nutrition in adults: a multicentre survey in Europe.

This registry describes a multicentre experience of Home Parenteral Nutrition (HPN) in nine European countries covering 27 centres and 194 patients. The main purpose of this study was to evaluate the quality of life and prognosis of patients on HPN. Patients started HPN at 44 +/- 1 years old (mean +/- SEM), and received 200 courses of HPN for a mean of 12 +/- 1 months representing a cumulative duration of 207 years. The four commonest indications for HPN were inflammatory bowel disease (30%), mesenteric vascular disease (21%), malignancy (17%) and radiation enteritis (13%). The nutritional status during HPN was clinically normal or subnormal in 93% of cases. The yearly incidence of catheter related complications leading to a catheter change was 0.74, sepsis accounting for half of this. The duration of hospital readmission for HPN complications was 4 +/- 1% of time spent at home, which represents 2 weeks per year and 41% of the total readmission time. Mortality was mainly influenced by the underlying disease since only 3% of patients died of HPN complications. A good social rehabilitation was observed in 52% of patients who during treatment recovered their pre-HPN occupational status. The poorest social rehabilitation was observed in patients over 65 years of age, and patients with malignancies and radiation enteritis, who also had the poorest prognosis. Caution seems necessary before recommending HPN in these patients.

Journal Article↗

Acral erythema and systemic toxicity related to CHA induction therapy in acute myeloid leukemia.

Seventy-two adult patients with previously untreated acute myeloid leukemia received the CHA regimen as induction chemotherapy: CCNU 80 mg/m2 on day 1, Adriamycin 35 mg/m2 i.v. on days 1, 2 and 3, and continuous infusion of cytarabine 100 mg/m2/24 h from day 1 to 10. Forty-nine patients (68%) presented at least one of the following symptoms: acral erythema with dysesthesias in the palms and/or soles (39%); cholestatic hepatitis (39%); profuse sterile diarrhea associated with abdominal distention (33%); acute cerebellar dysfunction (32%) and non-cardiogenic pulmonary edema (21%). Most of these toxic symptoms appeared 8-20 days after the first dose. As these clinical features were absent or exceptional in patients treated with another regimen within a controlled trial, they are reported as toxic-side-effects of the chemotherapy regimen. Acral erythema was found to be predictive of complete remission (P less than 0.01, odds ratio: 6.33); neurotoxicity was prognostic for death in aplasia (P less than 0.05); the absence of any of the five symptoms was associated with failure of the induction regimen (P less than 0.02).

Adolescent↗