Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

Education of patients with arterial disease. A plan for the use of Expert System in angiology via Minitel

We are presenting a computer program requiring the use of an Expert System accessible by Minitel, intended for patients with arterial disease and their attending physician. The objective is not to make a diagnosis, but to train the patients in applying health measures to the handling and prevention of his/her disease. While remaining anonymous, the patient may consult the program at home, without any time constraint. Only the patient's physician can authorize him/her to have access to the program. The Expert System may adjust the answers to the patients according to the past history and recent data. Contrary to a computer program, new knowledge does not impair the functioning of the system. The physician has access to simplified modules regarding his patient, and specific modules regarding the treatment. Such a system would help general practitioners in following his patient and would facilitate the Doctor-Patient relationship during consultations.     

Limitations of efficacy of chemotherapies in schizophrenia]

The concept of treatment-resistant schizophrenia cannot be defined as this of resistant depression: schizophrenia is a long-term illness; its evolution is almost always influenced by neuroleptics--but complete recovery is rare. French psychiatry tends to use clinical-empirical criteria, while english speaking studies prefer quantitative criteria, by extended use of clinical and psycho-social scales. The definition of resistant schizophrenia by Kane et al. is a typical example of this method of work. We propose to overview the limits of neuroleptics efficiency in schizophrenia from three groups of studies: a) The effects of maintenance therapy: 24 studies of the last twenty years show that 2/3 of schizophrenics under neuroleptics maintain their remission over one or two years, opposed to less than 1/3 of those who discontinue their treatment. These data seem to be independant from the method of the study, the choice of the neuroleptic drug, the dose and the way of administration (per os or depot treatment). b) A second group of studies tries to define the clinical characteristics of treatment-resistant schizophrenia. French psychiatry uses an empirical graduation of neuroleptics clinical efficiency: these drugs are more effective on hallucinations than on delusional ideas--they are more effective on recent and acute hallucinations and delusions than on those of which course is chronic. Other studies specify predictive factors of poor response to neuroleptics, as few affective symptoms and presence of negative symptoms--a controversed factor. c) Not clinical factors of poor neuroleptics efficiency in schizophrenia begin to be studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sparing of perceptual implicit memory despite suppression of the electrophysiological word repetition effect: a study with general anesthetic isoflurane.

OBJECTIVE: Much effort has been devoted to the search for the neurophysiological correlates of implicit memory. A commonly held view is that the early portion (250-500 ms) of the event-related potential (ERP) word repetition effect reflects processes important for perceptual implicit memory whereas the latter portion reflects processes implicated in explicit memory. It is, however, difficult to disentangle with certainty the relative contributions of each form of memory on ERPs since both forms co-exist in normal subjects. To dissociate ERP effect related to implicit and explicit memory, we used isoflurane sedation in normal subjects to suppress explicit remembering while sparing implicit memory. These ERPs were compared with those of non-medicated control subjects. METHODS: Thirteen subjects performed an incidental encoding task for words presented auditorily during the inhalation of a subanesthetic dose of isoflurane. After termination of isoflurane administration, we assessed free recall and recorded ERPs during a syllable completion task (implicit memory) and during a passive listening task (ERP repetition effect). Eleven non-medicated control subjects were tested in a similar manner. RESULTS: The controls showed robust early and late ERP repetition effect. The isoflurane group had implicit memory without free recall and showed no ERP repetition effect. CONCLUSIONS: These findings failed to show an association between any part of the repetition effect and perceptual implicit memory. The results are consistent with the view that processes linked to explicit memory contribute to the ERP repetition effect since there was a marked difference in free recall between the control and isoflurane groups. SIGNIFICANCE: The present study shows that the reversible alterations of memory by general anesthetics can be used to study the neurophysiological correlates of memory processes.     

Value of Doppler ultrasound for the diagnosis of renal artery stenosis in children

To evaluate the reliability of Doppler ultrasonography (US) in identifying children with renal artery stenosis (RAS) among those with hypertension, we compared Doppler US results in 22 hypertensive children (mean age 8.9±4.3 years), with (13 cases) and without RAS at angiography, and in 33 normotensive children (mean age 8.8±4.7 years). We observed 2 false-negatives and 2 false-positives with Doppler US. Of the 2 false-negative diagnoses, 1 had RAS on an accessory renal artery located behind a normal upper polar artery and the other was observed in a patient with bilateral multiple stenosis of the very distal segments of renal arteries. The 2 false-positive diagnoses were due to sinuous left renal artery and to technical reasons, respectively. In another patient, Doppler US showed a tight RAS, while arteriography was normal. RAS was subsequently confirmed by a second arteriography. Peak systolic velocity values of Doppler US were significantly higher in patients with proven angiographic RAS (3.44±0.66 m/s) than in hypertensive patients with normal renal arteries at angiography (0.99±0.35 m/s, P <0.0001) and normotensive healthy children (1.04±0.23 m/s, P <0.0001). With the use of multiple views, and the experience acquired with practice, false-negatives or false-positives due to the geometry of the renal artery can be avoided. Nevertheless, very distal stenosis can be missed by Doppler US. Received October 30, 1995; received in revised form April 16, 1996; accepted May 14, 1996     

Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP

We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[⁷⁶Br]BrQNP,E(-,-)-[⁷⁶Br]BrQNP andE(-,+)-[⁷⁶Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [⁷⁶Br]BrNH₄ and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M₂ selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M₁ selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[⁷⁶Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[⁷⁶Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[⁷⁶Br]BrQNP, which is displaced in higher amounts from M₂ mAChR-enriched structures, reveals an M₂ affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation.     

Avoiding drug-induced switching in patients with bipolar depression.

Antidepressant-induced switching is a major risk during the treatment of bipolar depression. Despite several clinical studies, questions remain regarding both the definition of these mood switches and the most appropriate therapeutic strategy to avoid this adverse effect.This review will first briefly consider the current guidelines for the acute treatment of bipolar depression. We will then review the mechanisms of action of antidepressant and mood stabilisers, and the switches induced by various types of antidepressant treatments, or triggered by antidepressant withdrawal, as well as by atypical antipsychotics. We then will address the risk of mood switch according to the type of mood stabiliser used. The propensity to mood switches in bipolar patients is subject to individual differences. Therefore we will describe both the clinical and biological characteristics of patients prone to mood switches under antidepressant treatment. However, the clinical characteristics of the depressive syndrome may also be a key determinant for mood switches. Various data help identify the most appropriate drug management strategies for avoiding mood switches during the treatment of bipolar depression. Selective serotonin reuptake inhibitors appear to be the drugs of first-choice because of the low associated risk of mood switching. Antidepressants must be associated with a mood stabiliser and the most effective in the prevention of switches seems to be lithium. Whatever the mood stabiliser used, effective plasma levels must be ensured. The optimal duration of antidepressant treatment for bipolar depression is still an open issue - prolonged treatments after recovery may be unnecessary and may facilitate mood elation. Moreover, some mood episodes with mixed symptoms can be worsened by antidepressants pointing to the need for a better delineation of the categories of symptoms requiring antidepressant treatment. Finally, as a result of this review, we suggest some propositions to define drug-induced switches in bipolar patients, and to try to delineate which strategies should be recommended in clinical practice to reduce as far as possible the risk of mood switch during the treatment of bipolar depression.     

Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma.

BACKGROUND: Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. OBJECTIVE: To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS: From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. RESULTS: The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). CONCLUSION: In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.     

High susceptibility of human dendritic cells to invasion by the intracellular pathogens Brucella suis, B. abortus, and B. melitensis

Bacteria from the Brucella genus are able to survive and proliferate within macrophages. Because they are phylogenetically closely related to macrophages, myeloid dendritic cells (DCs) constitute potential targets for Brucella bacteria. Here we report that DCs display a great susceptibility to Brucella infection. Therefore, DCs might serve as a reservoir and be important for the development of Brucella bacteria within their host.     

Polymères thiocarboxyliques, 1. Synthèse et étude de la polymérisation radicalaire de monomères dithiocarboxyliques

The syntheses and free-radical polymerizations of methyl and carboxymethyl 4-vinyldithiobenzoates are described as well as various copolymers. Copolymerisation parameters were determined for the copolymerizations of the methyl dithioester with styrene and with methyl methacrylate.