Recent advances in the immunology of xenotransplantation

The transplantation of tissue and organs between individuals of different species, that is xenotransplantation, engenders a variety of severe immune responses. Xenogeneic immune responses mediated by naturally occurring antibodies and complement lead to hyperacute and acute vascular rejection of vascularized organ grafts and may also cause vascular rejection of cell and tissue grafts. Under some circumstances, however, a vascularized organ graft may evade humoral rejection despite the presence of antidonor antibodies in the circulation of the recipient; this condition is called accommodation. Xenogeneic immune responses mediated by T-lymphocytes and natural killer cells may cause acute cellular rejection. The extent to which cellular rejection of xenografts resembles cellular rejection of allografts remains to be determined. New insights into the molecular mechanisms underlying the immune responses to xenotransplantation have shed new light on the pathogenesis of immunological disease and have allowed the development of specific immunomodulatory strategies that may facilitate clinical application of xenotransplantation.     

Productivity, quality, and patient satisfaction

CONTEXT: Although few data are available, many believe that part-time primary care physicians (PCPs) are less productive and provide lower quality care than full-time PCPs. Some insurers exclude part-time PCPs from their provider networks. OBJECTIVE: To compare productivity, quality of preventive care, patient satisfaction, and risk-adjusted resource utilization of part-time and full-time PCPs. DESIGN: Retrospective cohort study. SETTING: Boston. PARTICIPANTS: PCPs affiliated with 2 academic outpatient primary care networks. MEASUREMENTS: PCP productivity, patient satisfaction, resource utilization, and compliance with screening guidelines. RESULTS: Part-time PCP productivity was greater than that of full-time PCPs (2.1 work relative value units (RVUs)/bookable clinical hour versus 1.3 work RVUs/bookable clinical hour, P< .01). A similar proportion of part-time PCPs (80%) and full-time PCPs (75%) met targets for mammography, Pap smears, and cholesterol screening (P = .67). After adjusting for clinical case mix, practice location, gender, board certification status, and years in practice, resource utilization of part-time PCPs (138 dollars [95% confidence interval (CI), 108 dollars to 167 dollars]) was similar to that of full-time PCPs (139 dollars [95% CI, 108 dollars to 170 dollars], P = .92). Patient satisfaction was similar for part-time and full-time PCPs. CONCLUSIONS: In these academic primary care practices, rates of patient satisfaction, compliance with screening guidelines, and resource utilization were similar for part-time PCPs compared to full-time PCPs. Productivity per clinical hour was markedly higher for part-time PCPs. Despite study limitations, these data suggest that academic part-time PCPs are at least as efficient as full-time PCPs and that the quality of their work is similar.     

Spinal and bulbar muscular atrophy (SBMA): Somatic stability of an expanded CAG repeat in fetal tissues

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron degenerative disease caused by an expanded trinucleotide repeat. Unlike most other trinucleotide repeat diseases, SBMA shows limited meiotic instability, and evidence thus far indicates absence of somatic instability in adults. Data regarding the presence of fetal tissue somatic mosaicism is unavailable. We present a family in which a woman whose father had SBMA requested prenatal testing. After informed consent, molecular genetic evaluation showed the male fetus to carry the SBMA repeat elongation. Testing of fetal tissues after elective pregnancy termination showed no somatic mosaicism in the CAG repeat length. This is the first report of molecular genetic analysis of multiple tissues in an affected fetus, and only the second report of prenatal diagnosis in SBMA.     

Markedly different course of Friedreich’s ataxia in sib pairs with similar GAA repeat expansions in the frataxin gene

Friedreich’s ataxia (FA) is most frequently caused by intronic trinucleotide repeat expansions in the frataxin gene on chromosome 9. The broad clinical spectrum includes late-onset FA (LOFA) and FA with retained reflexes (FARR). The size of the GAA expansions accounts for most, but not all, of the clinical variability. We report the unusual occurrence of LOFA and FARR in two siblings of patients with classical early-onset FA in two families. In spite of the markedly different course of the disease, the respective siblings harboured GAA repeat expansions of similar size in leucocytes. Since haplotype-related variability is not likely among siblings, we suppose that this intrafamilial phenotype variability is due to somatic mosaicism, with the more severely affected siblings harbouring the larger expansions in spinal cord and other affected tissues. In view of these results, genetic counseling and predictions on the course of FA are particularly difficult, even if an expansion mutation is found. Received: 5 May 1998 / Revised, accepted: 15 July 1998     

Place learning and object recognition by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex

The acquisition of a water maze-based allocentric place learning task and an exploration based object recognition task were studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. None of the groups showed impairments of object recognition. Ablations of the prefrontal cortex caused a mild impairment in the acquisition of the place learning task. The two fimbria-fornix transected groups exhibited a severe impairment during the acquisition of this task. All groups reached criterion level task performance eventually. All groups were subjected to a number of behavioural and pharmacological challenges in order to elucidate the neural and cognitive mechanisms of this behavioural recovery. During a no-platform session both the fimbria-fornix transected group and the prefrontally ablated group demonstrated a normal preference for the former platform position. The combined lesion group, however, failed to show a similar preference for this position. The outcome of the pharmacological challenges demonstrated that while the task performance of all four groups relied equally on catecholaminergic mediation, only the task solution of the fimbria-fornix transected group was significantly impaired by disturbance of the catecholaminergic systems. The data indicated a high likelihood that prefrontal cortical mechanisms contribute to the recovery of allocentric place learning after fimbria-fornix transections.