Corneal allograft rejection in rabbits

We performed a phase I study to assess the therapeutic efficacy of an anti-T cell monoclonal antibody conjugated with ricin A-chain in a corneal graft rejection model. Corneal allografts were exchanged between Dutch and New Zealand rabbits. Rejections occurred within 16-22 days in untreated animals. Graft rejection was delayed by topical or retrobulbar cyclosporine, but not by subconjunctival injections of a murine anti-rabbit T cell monoclonal antibody, nor by either subconjunctival or intravenous F(ab')2-ricin conjugate.     

Cataract extraction in uveitis: comparison of aphakia and posterior chamber lens implantation.

We reviewed the charts of 39 patients (45 eyes) with uveitis who underwent cataract extraction (intracapsular or extracapsular) with or without implantation of a posterior chamber intraocular lens (IOL) at the Royal Victoria Hospital, Montreal, between 1981 and 1990. The nine eyes with Fuchs' iridocyclitis in which an IOL was implanted had good visual results and few postoperative complications. The 18 eyes with uveitis other than Fuchs' iridocyclitis that received an IOL did not show a greater risk of postoperative complications than those left aphakic (n = 17), and the postoperative visual acuity was comparable to that of the aphakic eyes. Although the numbers are small, we conclude that the presence of uveitis does not automatically exclude posterior chamber pseudophakia.     

Disseminated lupus erythematosus in children: guidelines about investigations during the initial evaluation and follow-up]

Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.     

The cellular mechanism of thalamic ponto-geniculo-occipital waves

The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. In most relay cells, reserpine-induced ponto-geniculo-occipital waves were associated with a transient depolarization that was often interrupted by a unitary inhibitory postsynaptic potential. The depolarization grew in size with membrane hyperpolarization and was accompanied by an increase in membrane conductance. The inhibitory postsynaptic potential is likely to have resulted from the activation of intrageniculate interneurons since perigeniculate cells were always inhibited during the occurrence of ponto-geniculo-occipital waves. Under reserpine, thalamic ponto-geniculo-occipital waves could also be triggered by peribrachial or auditory stimulation. These evoked ponto-geniculo-occipital waves were associated with intracellular events identical to those occurring spontaneously after reserpine administration. In addition, thalamic spindle oscillations were readily blocked by the occurrence of spontaneous or evoked ponto-geniculo-occipital waves. On the basis of the present results and those already published in the literature, the conclusion is reached that lateral geniculate ponto-geniculo-occipital waves result from a nicotinic activation of relay cells and from a parallel muscarinic inhibition of perigeniculate cells by peribrachial afferents. The functional significance of the ponto-geniculo-occipital activity is discussed on the basis of the antagonistic action of these signals on thalamic oscillations. It is proposed that these signals are the central correlates of orienting reactions elicited by sensory stimuli during waking (the so-called eye movement potentials) and by internally generated drives during paradoxical sleep.     

Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.     

Voltage-dependent 40-Hz oscillations in rat reticular thalamic neurons in vivo.

Extra- and intracellular recordings of thalamic reticular and relay neurons were performed in rats under urethane anaesthesia. Under this type of anaesthesia it was found that, throughout the whole reticular thalamic nucleus, a large proportion of cells (approximately 34%) discharged like clocks within a 25-60 Hz frequency band width (i.e. 40 Hz). Simultaneous recordings of pairs of reticular cells showed that the regular discharges of nearby units were not synchronous. Thus, the asynchronous 40-Hz firing of reticular thalamic cells was not correlated with any 40-Hz extracellular activity as revealed by the spectral analysis of the electroencephalogram and by recordings performed in various thalamic nuclei. In relay cells of the ventrobasal, ventral lateral and posterior thalamic nuclei, the regular firing of reticular thalamic neurons induced a rhythmic inhibitory modulation that was detected by the time-series analysis of the inhibitory postsynaptic potentials. In many relay cells, however, the disclosure of this inhibitory modulation required cellular depolarization since the resting potential in these cells was maintained at the reversal potential of the inhibitory events. Intracellular recordings of reticular thalamic cells showed that their regular firing was not driven in an all-or-nothing manner by 40-Hz synaptic inputs but rather that it depended upon the activation of a voltage-dependent pacemaker mechanism; this pacemaker activity was manifested by the presence of subthreshold oscillations that drove spike discharges and whose frequency was voltage dependent. In the context of data already published on the genesis of 40-Hz oscillations in the brain, and given the key position of reticular thalamic neurons in thalamocortical networks, the present results indicate that the reticular thalamic nucleus might play a pacemaker function in the genesis of 40-Hz oscillations in the thalamus and cortex during states of focused arousal.     

Cost-effective use of autologous bone marrow transplantation: few answers, many questions, and suggestions for future assessments

High dose chemotherapy with the support of autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cells (PBPC) has been increasingly used in a variety of haematological and epithelial cancers over the last decade. The rationale of this approach is to overcome the chemotherapy resistance of tumour cells by increasing the dose of cytotoxic drugs. However, the clinical benefit of dose-intensification has been difficult to prove. Almost all studies of ABMT have been done without randomised comparisons with the standard form of therapy for a specific condition. From an economic perspective, the cost of ABMT has been steadily decreasing with improvements in supportive care primarily. Still, current ABMT cost estimates range from $US70 000 to $US150 000 for each uncomplicated procedure. Despite the lack of compelling evidence in support of dose-intensification, ABMT has become a default standard of care after relapse for many patients with lymphoma or leukaemia. We used a decision analysis model to estimate the cost effectiveness of the timing of ABMT in relapsed Hodgkin's disease. The model illustrates the difficulty of using available clinical trial data when follow-up of promising early reports is not available. The model showed that in most situations the optimal strategy is ABMT in second relapse despite growing consensus that immediate ABMT is the treatment of choice. ABMT for women with high-risk or early metastatic breast cancer is one of the most controversial areas in clinical oncology. In the US, several ongoing major randomised trials are addressing the role of ABMT in breast cancer. Using a Markov process we found that ABMT is the preferred strategy under almost all assumptions. The size of the benefit and cost effectiveness of ABMT varied markedly depending on the assumptions made. The model does not supplant the need for randomised trials that concurrently measure efficacy, quality of life, and resource utilisation. However, such analyses point out the critical areas where costs could be cut substantially without effecting efficacy. Drawing conclusions about the cost effectiveness of ABMT for all conditions is hampered by the lack of randomised comparisons of efficacy. Concurrent economic appraisals of selected phase III comparative trials should be considered since the supportive care costs associated with ABMT appear to be stabilising. However, the most important point is that randomised trials are the only mechanism for estimating the therapeutic effect of high dose chemotherapy.     

A sociodemographic and economic comparison of breast reconstruction, mastectomy, and conservative surgery

BACKGROUND: There are a variety of surgical choices for women with early-stage breast cancer, including breast-conserving surgery, mastectomy, or mastectomy plus reconstructive surgery. This report examines some of the factors that affect these choices and the costs of the various treatment options. METHODS: Data from the Virginia Cancer Registry were linked to insurance claims from the Trigon Blue Cross and Blue Shield Company for women with local and regional staged breast cancer from 1989 to 1991 in Virginia. Multivariate analyses and cost studies were performed. RESULTS: There were 592 women who underwent breast-conserving surgery (BCS, 26%), mastectomy (58%), or mastectomy plus reconstruction (16%). Increasing age reduced the use of reconstruction. The choice of reconstruction was not affected by tumor size, nodal status, or race. Sixty percent of women had immediate breast reconstruction at the time of mastectomy; the majority had the implant procedure. The cost of BCS ($21,582) was higher than that of mastectomy ($16,122, P < .01). The costs for BCS and mastectomy were significantly lower than for mastectomy plus reconstruction ($31,047, P < .05). The 2-year cost for immediate reconstruction was $8200 less than for delayed procedures and was similar to the cost of BCS. CONCLUSIONS: Age was the driving force in reconstruction decisions. Clinical factors such as tumor size and nodal status were more important for the choice between BCS and mastectomy. There are significant cost differences between the various procedures. For a similar cosmetic outcome, BCS is less expensive than breast reconstruction. When reconstruction is required, a simultaneous procedure is less expensive.     

Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).

PURPOSE: We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin. RESULTS: The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019). CONCLUSION: Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.