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.     

Rheumatic fever: clinical profile of the initial attack in India

The clinical profile of acute rheumatic fever in developing countries is frequently reported to differ from that in developed countries. This probably arose because a distinction was not made between the manifestations of the initial attack and those of a recurrence. Here, we report the patterns of presentation and clinical features of 100 cases of carefully determined initial attacks of rheumatic fever. As many as half the patients had carditis, and, of these, 50% exhibited congestive cardiac failure. This high incidence arises because in developing countries with limited health-care facilities patients continue to be physically active during the long pre-admission period. The study confirms that the clinical profile of the initial attack of rheumatic fever in developing countries is in most respects not unlike that in developed countries.     

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.     

Antiparkinsonian activity and behavioural effects of newer quinazolinones

Sixteen new compounds 2-methylamino substituted phenyl-3-substituted anilino 4 (3H) quinazolinones (3-18) were prepared. All the compounds were evaluated for their antiparkinsonian activity and compared with bromocriptine. Compounds 10,15 and 18 showed better activity. These compounds also bind with the dopamine receptors in striatal membrane preparations of rat brain.     

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.