Outcome of live related and live unrelated renal transplants

Summary: This study compares the outcomes of 229 renal transplants, of which 156 were live related renal transplants done at our centre and 73 unrelated transplants done at other centres but followed up at our centre. All the patients were on triple immunosuppression for periods varying between 9 months and 1 year. Patient characteristics, rejections, infections and 1 and 5 years patient and graft survival were analyzed in the two groups. the outcome of patients who continued on cyclosporine beyond 1 year was compared to those who discontinued cyclosporine at 1 year. Males predominated (191 vs 38) in both groups, while younger patients (<50 years) predominated in live related group (152 vs four). There was no difference in the incidence of infection, rejection, graft dysfunction, graft loss or death between the two groups. the 1 and 5 year patient survival in the related and unrelated group, (93.7% and 71.4% vs and 85% and 66%) and graft survival (90.4% and 69.4% vs 83.3% and 65.4%) were similar. However, in the unrelated group, patients who discontinued cyclosporine had a higher incidence of rejections (38% vs 14%) and graft loss (43% vs 11.8%), while in the related group no such difference was found. It is concluded that 1 and 5 year patient and graft survival is comparable between live related and live unrelated transplantation. However, in the unrelated group it is necessary to continue cyclosporine beyond 1 year in order to achieve comparable results.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.     

Effect of sperm preparation with TEST yolk buffer on sperm-binding capacity under hemizona assay conditions

Summary. The study was conducted to evaluate the diverse effect and clinical significance of TEST yolk buffer treatment on sperm samples of 128 infertile men. Sperm samples were incubated with TEST yolk buffer and control medium (Ham's F-10) at room temperature for 2 h. The hemizona indices (mean ± SE) of the TEST yolk buffer and medium-treated sperm samples were 29 ± 2.3% and 22 ± 1.6%, respectively. Inspection of the individual response of each sperm sample to TEST yolk buffer revealed that 63 samples (49%) improved (double the interassay variation = 28%) their binding to zona pellucida, 36 (28%) remained unchanged, whereas the binding capacity of 29 samples (23%) decreased. Furthermore, TEST yolk buffer treatment of 24 samples (19%) resulted in an increased binding beyond the hemizona index threshold set up at 23%. This level was previously shown to be the cut-off point between fertile and infertile sperm samples. It was concluded that when applied to an unselected group of infertile men, TEST yolk buffer significantly increased sperm binding capacity to the zona pellucida. However, only 19% of the sperm samples showed improvement with clinical significance. The other sperm samples may have improved, remained unchanged or even deteriorated independently on basic sperm variables. Thus, the effect of TEST yolk buffer treatment on sperm binding should be tested prior to its clinical use to avoid possible damage to certain sperm samples.     

Acute severe combined demyelination

We present a second case in which Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) appeared simultaneously, both in acute and fulminant form. The patient, a 10-year-old girl, presented with acute onset of coma and flaccid, areflexic quadriparesis. The elevated CSF protein levels and delayed F waves fulfilled the criteria of GBS and an MRI study revealed extensive multifocal demyelination compatible with a diagnosis of ADEM. Prompt clinical response followed by complete recovery was achieved by treatment with corticosteroids. It is suggested that acute severe combined demyelination might constitute a separate entity in which the demyelinating process, involving simultaneously the central and the peripheral nervous systems, indicates immune response against a component of the myelin of one system carrying cross-antigenicity with the other.     

Correlation between sperm penetration into the human zona pellucida and in vitro fertilization rates

Summary.  Sperm penetration into the zona pellucida of unfertilized oocytes, and its correlation with in vitro fertilization rates of the sibling oocytes, were assessed. This was performed in order to evaluate the prediction rate of the sperm penetration test into the zona pellucida. Unfertilized oocytes ( n =1872) from 371 cycles were pipetted through a microcapillary, and the remaining sperm cells penetrating the zona pellucida were counted. The mean (±SD) number of spermatozoa that penetrated the zona pellucida of unfertilized oocytes was 12.9±16.37. A significant correlation was found between the fertilization rate and the mean number of spermatozoa that penetrated into the zona pellucida of the unfertilized sibling oocytes (r = 0.48; P < 0.001), or the percent of unpenetrated zonae pellucidae in a cohort (r= —0.43; P < 0.001). However, a distinct variation in the number of spermatozoa that penetrated into the zona pellucida was detected. A step-wise regression analysis proved the number of spermatozoa penetrating the zona pellucida to be more predictive for fertilization rates than the variable of percent of unpenetrated zonae pellucidae. The results imply that although there is interdependence between penetration into the zona pellucida and fertilization rate, the predictive value of sperm penetration test for prognosis and future management after the first in vitro fertilization attempt, is limited.     

Cost–Utility Analysis of Paclitaxel in Combination with Cisplatin for Patients with Advanced Ovarian Cancer

The standard treatment for patients with advanced ovarian cancer (AOC) has been cyclophosphamide and cisplatin (CP). Recently, the results of a large randomized comparative trial demonstrated that the combination of paclitaxel and cisplatin (TP) provided a progression-free survival benefit of 5 months. In this study, a cost–utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of the TP combination. Twelve AOC patients who received treatment with TP were matched for age and disease stage on a 1-to-2 basis with a CP control. Total hospital resource consumption was then collected for all patients. Treatment preferences were estimated from a cohort of 20 patients and 40 healthy female volunteers using the time trade-off technique. The outcomes were then generated through a decision-analytic model. First-line treatment costs with TP were approximately fourfold greater on a per-cycle basis than the CP alternative (Can$1911 vs Can$459). When progression-free survival benefit and patient treatment preferences were incorporated into the analysis, the results of the decision model revealed an incremental cost between Can$12,000 and Can$24,000 per quality-adjusted progression-free year with the TP protocol. Even though the TP combination has a considerably higher drug acquisition cost, the results of the current analysis suggest that this new chemotherapy regimen does provide patients with substantial quality-adjusted progression-free survival benefit at a reasonable cost to the Canadian health care system.     

Studies on capsaicin inhibition of chemically induced lipid peroxidation in the lung and liver tissues of rat

Previous work from this laboratory has already indicated that capsaicin, stabilizes the rat lung membrane lipid system on long-term treatment. This stabilization of the membrane is further supported by our present findings that capsaicin pretreatment causes significant inhibition of various chemically induced lipid peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes induced by different chemical irritants such as chloroform, dichloromethane, carbon tetrachloride as well as ferrous sulphate.     

Neural networks counting chimes.

It is shown that the ideas that led to neural networks capable of recalling associatively and asynchronously temporal sequences of patterns can be extended to produce a neural network that automatically counts the cardinal number in a sequence of identical external stimuli. The network is explicitly constructed, analyzed, and simulated. Such a network may account for the cognitive effect of the automatic counting of chimes to tell the hour. A more general implication is that different electrophysiological responses to identical stimuli, at certain stages of cortical processing, do not necessarily imply synaptic modification, a la Hebb. Such differences may arise from the fact that consecutive identical inputs find the network in different stages of an active temporal sequence of cognitive states. These types of networks are then situated within a program for the study of cognition, which assigns the detection of meaning as the primary role of attractor neural networks rather than computation, in contrast to the parallel distributed processing attitude to the connectionist project. This interpretation is free of homunculus, as well as from the criticism raised against the cognitive model of symbol manipulation. Computation is then identified as the syntax of temporal sequences of quasi-attractors.