Reduction of Immunosuppression for Transplant-Associated Skin Cancer: Rationale and Evidence of Efficacy

BACKGROUND: Solid organ transplant recipients may develop numerous or life-threatening skin cancers. In addition to aggressive standard treatment of skin cancer, reduction of immunosuppression has been considered an adjuvant therapeutic strategy, albeit without direct proof of efficacy. OBJECTIVE: To review the rationale for and evidence supporting the efficacy of reduction of immunosuppression for severe skin cancer in transplant recipients. METHODS: Review of the literature regarding direct and indirect evidence on reduction of immunosuppression for transplant-associated skin cancer. RESULTS: Although there are no randomized controlled trials of reduction of immunosuppression as a therapeutic intervention for transplant patients with skin cancer, multiple lines of evidence suggest that this strategy may be an effective adjuvant therapy. A randomized trial has demonstrated a lower incidence of skin cancer in transplant recipients after reduction of immunosuppression, albeit in a cohort not previously affected by skin cancer. Case series of reduction or cessation of immunosuppression demonstrate a lower incidence of skin cancer or improved outcomes of preexisting skin cancer. Lower overall immunosuppression is associated with a lower incidence of skin cancer. Multiple cancers affecting the skin have been shown to regress with reduction of immunosuppression. CONCLUSIONS: Reduction of immunosuppression may be an effective adjuvant therapeutic strategy when confronting severe transplant-associated skin cancer. The risks of reduction of immunosuppression must be better defined, and randomized trials of this strategy are necessary.     

Immunocytochemical identification of outer segment proteins in the rd chicken

Immunoreactivities of two monoclonal antibodies (MAbs) that recognize cone photopigments were tested in the retinas of congenitally blind retinal degenerate (rd) chicks and compared to normally sighted carrier chicks, heterozygous for the mutation. MAb OS-2 had been previously determined to label rod and most cone outer segment membranes in normal chick retinas and is believed to bind to an epitope that is common to several photopigments in chickens. MAb COS-1 labels specifically middle-to-long-wavelength-sensitive cone photopigments in a number of vertebrate species. In rd chicks MAb OS-2 labeled the same number of rod outer segments at the same densities as carrier chicks. However, cone outer segments were less frequently and significantly less heavily labeled with this MAb at all ages tested (1 day, 1 week and 2 weeks post hatching). MAb COS-1 labeled the same number of cone outer segments in both rd and carrier retinas at 1 day of age, however, those outer segments that were labeled in rd specimens had significantly fewer gold particles on them. At both 1 week and 2 weeks of age, rd chick retinas had a significant reduction in numbers of cone outer segments labeled by COS-1. These findings support the hypothesis that the cone photopigment protein is abnormal in the rd chick model of hereditary blindness and retinal degeneration.     

Ultrastuctural studies of the primate lateral geniculate nucleus: Morphology and spatial relationships of axon terminals arising from the retina,visual cortex (area 17), superior colliculus,parabigminal nucleus,and pretectum of Galago crassicaudatus

The electron microscopic autoradiographic tracing method has been used to examine the morphology and postsynaptic relationships of five projections (retina, cortical area 17, superior colliculus (tectal), parabigeminal nucleus, and pretectum) to the dorsal lateral geniculate nucleus of the greater bush baby galago crassicaudatus. Retinal terminals have been examined in the contralaterally innervated layer of each of the three matched pairs [parvi-(X-cell), magno- (Y--cell), and koniocellular (small, W-cell)] of geniculate layers. These terminals are large and contain pale mitochondria and round vesicles (RLPs). RLPs are presynaptic to juxtasomatic regions of parvi-and magnocellular neurons. In contrast, RLPs innervate more distal regions of konicellular neurons. Labeled cortical, tectal, and parabigeminal terminals are relatively small and contain round vesicles na dark mitochondria. Cortical terminals in each of the three representative layers are presynaptic to small diameter dendrites. No convergence of cortical and retinal terminals has been seen in any layer. Labeled tectal and parabigminal terminals are found primarily in the koniocellular layers, but the latter are also seen in all other layers. Tectal and parabigeminal terminals have been observed converging with retinal terminals on dendrites of some koniocellular neurons. Labeled pretectogeniculate terminals contain densely packed pleomorphic vesicles, dark mitochondria, and a dark cytoplasmic matric. These terminals, which are present in each of the representative layers, are presynaptic to conventional dendrites and profiles containing loosely despersed pleomorphic vesicles and a pale cytoplasmic matrix. © 1994 Wiley-Liss, Inc.     

Diverse implications of a national health crisis: A qualitative exploration of community nurses' SARS experiences.

The purpose of this study was to enhance our understanding of the influence of the SARS crisis on the work and personal lives of community nurses.A total of 941 community nurses employed in a range of health-care settings in the province of Ontario, Canada, provided qualitative information about their perceptions of the impact of SARS in their workplace and in their personal lives. Themes and subthemes from the data were organized into 2 categories: The Experience (operational, organizational, and personal narratives), and Learning from the Experience (opportunities for personal learning, professional and policy development, and insight into policy and administrative implications). The findings are discussed within a framework of the learning opportunity presented by the crisis at the local, national, and international levels. The roles of effective communication, emergency response coordination, and education are considered with respect to policy development and administrative responses to infectious disease protocol. The findings are particularly relevant at this time of heightened fear of global epidemics.     

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.     

Insulin production by pancreatic islets of obese-hyperglycemic mice cultured for one week in different glucose concentrations.

Culture of pancreatic islets isolated from obese-hyperglycemic mice (gene symbol ob) for one week in media containing widely different concentrations of glucose (3.3, 5.6 or 16.7 mM) was found to markedly influence the functional behaviour of the islet B-cells. Thus, the insulin content of islets cultured at 3.3 or 16.7 mM glucose (subphysiological or supraphysiological glucose concentrations respectively) was markedly reduced. Islets cultured in 5.6 or 16.7 mM glucose displayed a normal insulin secretory response when stimulated with glucose, whereas islets cultured in a subnormal glucose concentration (3.3 mM) showed a reduced insulin response to glucose stimulation in batch type incubations and also lacked a second phase of insulin secretion in islet perifusion experiments. The rate of insulin biosynthesis of non-cultured ob/ob islets was higher than that of islets from their lean siblings but culture for one week in 3.3 mM glucose induced a pronounced impairment of the insulin biosynthesis in islets of obese as well as lean mice. The present data indicate that the hyperfunction of the islets of the ob/ob mouse at least in part is a reversible phenomenon, suggesting that inherent properties of islet B-cells do not act as "primary" factors in the development of the obese-hyperglycemic syndrome.