Disease management

The disease management approach to patient care seeks to coordinate resources across the healthcare delivery system. The growing interest in evidence based medicine and outcomes, and a commitment to integrated care across the primary, secondary, and community care sectors, all contribute to making disease management an attractive idea. A combination of patient education, provider use of practice guidelines, appropriate consultation, and supplies of drugs and ancillary services all come together in the disease management process. But its effectiveness is largely untested, so evaluation is essential.     

Cerebral malaria

There is no established protocol for selection among the different retentive material-attachment combinations for clasps other than tradition or laboratory preference. Various wrought-wire, cast-metal, and thermoplastic materials were subjected to several fabrication procedures and tested in a custom-designed force displacement apparatus. The wrought wires included ADA Spec. No. 7 type I and type II alloys and other precious and nonprecious alloys. A graphic means was devised to allow the rational selection of wrought-wire clasp-arm combinations for placing clasps on canine and premolar teeth. Guidelines for using straight wire data for curved wire applications are indicated.     

Cement versus cementless fixation in total knee arthroplasty

A prospectively studied group of 55 uncemented Press Fit Condylar total knee arthroplasties was compared retrospectively with a matched group of 51 cemented Press Fit Condylar total knee arthroplasties at a mean of 10 years after operation. For the cemented group, the pain and function scores improved from 32 and 45 preoperatively to 95 and 77, respectively. For the uncemented group the scores improved from 33 and 50 preoperatively to 93 and 60, respectively. There were 10 revisions in the uncemented group for femoral or tibial aseptic loosening or osteolysis compared with two revisions in the cemented group. Exclusive of problems related to patellar metal backing, survival to revision for aseptic failure or radiographic loosening was 72% in the uncemented group and 94% in the cemented group at 10 years. A significantly higher revision rate was found in the uncemented compared with cemented total knee arthroplasty of the Press Fit Condylar design.     

Frequent clones of p53-mutated keratinocytes in normal human skin

The multiple genetic hit model of cancer predicts that normal individuals should have stable populations of cancer-prone, but noncancerous, mutant cells awaiting further genetic hits. We report that whole-mount preparations of human skin contain clonal patches of p53-mutated keratinocytes, arising from the dermal-epidermal junction and from hair follicles. These clones, 60-3000 cells in size, are present at frequencies exceeding 40 cells per cm2 and together involve as much as 4% of the epidermis. In sun-exposed skin, clones are both more frequent and larger than in sun-shielded skin. We conclude that, in addition to being a tumorigenic mutagen, sunlight acts as a tumor promoter by favoring the clonal expansion of p53-mutated cells. These combined actions of sunlight result in normal individuals carrying a substantial burden of keratinocytes predisposed to cancer.     

Study of the beta -delayed neutron decay of 18N

The shortage of suitable liver donors for children has motivated the use of ABO-incompatible (ABO-I) grafts for transplantation in urgent situations. However, survival after ABO-I liver grafts has been reported at about 30% as compared with 80% in cases of ABO-identical or -compatible liver grafts. This difference has been attributed to antibody-mediated, hyperacute or chronic liver rejection, due to preformed ABO antibodies (alloantibodies). In this study, we report our results with ABO-I livers in children without alloantibodies at the time of transplantation. From January 1988 to June 1993, 143 OLT were performed in 122 children. Eight children received 8 ABO-I liver grafts. Of these, 7 patients were included in the study. All 7 were alloantibody free before OLT. Five children were spontaneously alloantibody free, while in 2 children, the plasma alloantibodies were eliminated before and after transplantation using intravenous infusion of specific blood group antigens of the donor blood group (soluble antigens). Immunosuppression consisted of a triple-drug treatment combining CsA, AZA, and steroids. The follow-up period was between 10 and 48 months. One child died from a surgical complication. Six children survived, but 1 died 10 months later from intestinal obstruction. There were no graft losses and no episodes of hyperacute or chronic rejection. The graft and patient survival rate was 71%. There was a 28% incidence of rejection, but all were mild (requiring steroid boluses only). Our results suggest that the absence of ABO alloantibodies at the time of and after transplantation can protect ABO-I liver grafts against antibody-mediated rejection, whether hyperacute or chronic, and that soluble antigens are effective in eliminating alloantibodies in children.     

Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat

In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation.     

Engineering dental pulp-like tissue in vitro

Injury or infection of adult dental pulp often necessitates root canal therapy. This terminates dentin formation and subsequent tooth maturation. In addition, the synthetic materials currently utilized to replace lost tooth structure are not capable of completely replacing the function of the lost tissue, and often fail over time. This report describes a technique to engineer new pulp-like tissues utilizing cultured cells and synthetic extracellular matrices. Fibroblasts were obtained from human adult dental pulps and multiplied in culture. These cells were subsequently seeded onto synthetic matrices fabricated from fibers (approximately 15 microns in diameter) of polyglycolic acid (PGA). The pulp-derived fibroblasts adhered to the fibers, proliferated, and formed a new tissue over 60 days in culture with a cellularity similar to that of native pulp. These tissues may find application in the regeneration of oral tissues and may provide novel systems in which to study the biocompatibility of materials and chemicals used in dentistry.     

Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

Distinctiveness and Correlation in Conceptual Structure: Behavioral and Computational Studies.

Patients with category-specific deficits have motivated a range of hypotheses about the structure of the conceptual system. One class of models claims that apparent category dissociations emerge from the internal structure of concepts rather than fractionation of the system into separate substores. This account claims that distinctive properties of concepts in the living domain are vulnerable because of their weak correlation with other features. Given the assumption that mutual activation among correlated properties produces faster activation in the normal system, the authors predicted a disadvantage for the distinctive features of living things for unimpaired adults. Results of a speeded feature verification study supported this prediction, as did a computational simulation in which networks mapped from orthography to semantics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)