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.     

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     

Orbital and muscular relapse of Burkitt's lymphoma

We report the case of a child presenting with abdominal Burkitt's lymphoma in whom a relapse presented as orbital and muscle involvement. This clinical feature is extremely rare. Two muscle and one orbital biopsies were necessary to obtain proper diagnosis. A new extension check-up showed bone marrow invasion and normal cerebrospinal fluid. This relapse was successfully treated by conventional chemotherapy and consolidated with high-dose chemotherapy, total body irradiation and autologous bone marrow transplantation. Eighteen months after transplantation, the child may be considered as definitively cured.     

Exploratory hierarchy and surgical indications for carotid surgery in patients with coronary disease

The major cause of death from carotid artery surgery (1.2% in 1984 in this series) is still coronary disease and myocardial infarct. A series of 50 patients were randomly selected for detailed study of post-operative cardiologic complications and the following sequelae were noted: mortality = 1 myocardial infarct; morbidity = 1 myocardial infarct, 3 documented anginal pains, 8 repolarization disorders, 4 benign ventricular arrhythmias. Analysis of these complications and a literature review demonstrated: the high frequency of combined carotid artery and coronary artery stenosis even in asymptomatic patients (25 to 40% of cases); the elevated percentage of complications in patients with symptomatic coronary disease (mortality risk multiplied by ten), hypertension or arterial disease; the low effect of age taken alone as risk factor. Pre-operative explorations to detect angina, particularly when latent and asymptomatic, should include a questionnaire, strict patient clinical examination and detailed reading of electrocardiogram tracings. An effort test should be performed as a function of results and patients' medical history and when positive should lead to coronarography in patients under 70 in good general condition, and when doubt persists after the effort tests. The indication for surgical treatment is dependent on results of these explorations: Carotid artery surgery (stenosis with high cerebral risk) should be performed under pre- and post-operative myocardial protection in patients with coronary artery disease who are too old or inoperable for cardiac reasons. Simultaneous myocardial and cerebral revascularization in the presence of severe lesions and at equivalent risk of progression. First intention carotid artery surgery for bilateral stable lesions with subsequent simultaneous myocardial and cerebral revascularization. First intention carotid artery surgery in case of cerebral ischemia with coronary artery shunt surgery at a later stage. Improved exploration of patients and close cooperation between cardiologists, anaesthetists and surgeons should allow patients at high risk to be operated upon under improved conditions of safety.     

Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Idiopathic Parkinson's disease (PD) may possibly be caused by one or more unidentified neurotoxins present in the environment, or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in humans, lower primates and mice that closely resemble those found in PD. Because the mechanisms of neuronal damage in both idiopathic PD and in the MPTP model of PD may involve free radical formation in the substantia nigra, antioxidants might protect dopaminergic neurons. Previously, we found that both alpha-tocopherol and beta-carotene partially protected mice against MPTP. However, in the experiments described in this paper, neither alpha-tocopherol nor beta-carotene, each administered in massive doses, had any demonstrable protective effect for dopaminergic nigrostriatal neurons in marmosets injected with low doses of MPTP. Without more knowledge about the identity of the neurotoxin(s) causing idiopathic PD, and their mechanism of action, it is not possible at this time to predict whether these 2 antioxidants might be clinically useful in preventing or ameliorating PD.     

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.     

Diverse implications of a national health crisis: A qualitative exploration of community nurses' SARS experiences.

The purpose of this study was to enhance our understanding of the influence of the SARS crisis on the work and personal lives of community nurses.A total of 941 community nurses employed in a range of health-care settings in the province of Ontario, Canada, provided qualitative information about their perceptions of the impact of SARS in their workplace and in their personal lives. Themes and subthemes from the data were organized into 2 categories: The Experience (operational, organizational, and personal narratives), and Learning from the Experience (opportunities for personal learning, professional and policy development, and insight into policy and administrative implications). The findings are discussed within a framework of the learning opportunity presented by the crisis at the local, national, and international levels. The roles of effective communication, emergency response coordination, and education are considered with respect to policy development and administrative responses to infectious disease protocol. The findings are particularly relevant at this time of heightened fear of global epidemics.