Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n=13) or a mean dosage of 0.07 mg/kg per day (n=4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient,P<0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in preadolescents receiving FK-506 but no prednisone (P<0.02 andP<0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.     

Human cytomegalovirus infection up-regulates interleukin-8 gene expression and stimulates neutrophil transendothelial migration.

Virus-induced alterations in the cellular expression of chemokines may be important in directing the migration of specific leucocyte subsets to sites of infection, thereby playing a pivotal role in viral pathogenesis. We show here that cytomegalovirus (CMV) infection of human fibroblasts resulted in significantly increased expression of the C-X-C or alpha-chemokine interleukin-8 (IL-8), at both the mRNA and protein levels. Increased IL-8 production was seen following infection with the high passage laboratory CMV strains AD169, Towne, or Davis, as well as the low passage clinical CMV isolates Toledo or C1F. The increase in IL-8 production had functional consequences, as demonstrated by the ability of supernatants from CMV-infected fibroblasts to significantly enhance neutrophil transendothelial migration. The latter was independent of alterations in adhesion molecule expression on the endothelial cells, and was abrogated by neutralizing antibodies specific for IL-8. Direct infection of endothelium with the endothelial cell-tropic CMV strain C1FE, also resulted in enhanced neutrophil transendothelial migration. Neutrophils play an important role in the dissemination of CMV throughout the body, and thus CMV-induced neutrophil recruitment would be expected to enhance CMV dissemination. Increased production of chemokines in response to CMV infection could also disrupt the fine balance between a beneficial and a destructive immune response, thereby potentially contributing to pathology.     

Reconstruction of the fossa navicularis

Fossa navicularis strictures have troubled urologists for years. Although several flap procedures have been described none truly leaves a normal-appearing penis postoperatively. A new technique is described of the reconstruction of the fossa navicularis with a ventral transverse island flap on a broad, dependable pedicle. All 5 patients who have undergone the procedure have excellent cosmetic and functional results. The appearance of the penis postoperatively is normal, with a median followup of 17 months. Early reconstruction of fossa strictures may avoid the sequelae of more conservative attempts at management, thus, correcting the fossa stricture itself before the occurrence of penourethral stricture disease secondary to repeated dilations, meatotomy and internal urethrotomy.     

Velocity and flow quantitation in the superior sagittal sinus with ungated and cine (gated) phase-contrast MR imaging

Normal blood flow and velocity in the superior sagittal sinus were measured in 30 patients. A fast two-dimensional ungated phase-contrast (PC) pulse sequence was compared with a peripherally gated cine PC technique for velocity and flow quantitation. The same imaging parameters were used for both methods. Measured values for mean velocity and flow obtained with the two methods were compared by using regression analysis and t testing. For blood flow, the correlation coefficient was 0.976. For velocity measurements, r was 0.950. Mean flow was 285 mL/min ± 19 with the ungated PC method and 281 mL/min ± 19 with the cine PC method. The mean velocities measured with the two methods were 12.94 cm/sec ± 1.1 and 13.59 cm/sec ± 1.1, respectively. There was no significant difference (paired t test) between the methods for mean flow or velocity data. This was true even though flow in the superior sagittal sinus is moderately pulsatile, as shown with the cine PC technique. The ungated PC method provided these data in 13 seconds versus 3.5 minutes for the cine PC method.     

Intravenous Gammaglobulin (IVIG): A Novel Approach to Improve Transplant Rates and Outcomes in Highly HLA-Sensitized Patients

Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their introduction, IVIG products were also found to be effective in the treatment of autoimmune and inflammatory disorders. Over the past 2 decades, the list of diseases where IVIG has a demonstrable beneficial effect has grown rapidly. These include Kawasaki disease, Guillain-Barre syndrome, myasthenia gravis, dermatomyositis and demyelinating polyneuropathy. Recently, we have described a beneficial effect on the reduction of anti-HLA antibodies with subsequent improvement in transplantation of highly HLA-sensitized patients as well as a potent anti-inflammatory effect that is beneficial in the treatment of antibody-mediated rejection (AMR). These advancements have enabled transplantation of patients previously considered untransplantable. These studies and relevant mechanism(s) of action will be discussed here.     

Should nurses be studying bioscience? A discussion paper

The growth of bioscience knowledge over the last two decades has increased the potential benefits of scientifically based patient care by contributing to the theory of clinical care. However, there is little evidence that knowledge, derived from the human biosciences is being fully incorporated into nursing theory and practice.Nursing has developed its own unique professional body of knowledge, heavily influenced by behavioural science. If nursing theory leans towards behavioural science, but practice is devoted to problems of biological disturbance, nursing may be facing a widening theory-practice gap, greater than other professions. The theory-practice gap in nursing may be widened by the exclusion of bioscience from nursing theory. Nurses' relative disinterest in the natural sciences can be attributed both to sociological reasons and to problems stemming from the symbol-object dichotomy that recur in the teaching of natural sciences. Reflection on practice and examination of education method are suggested as strategies for re-introducing bioscience into nursing theory and practice. A challenge facing nurse educators is the integration of biological science into the nurses' conceptual ecologies. For, if nursing fails to make bioscience its own, much of the clinical welfare of patients will become a medical monopoly.