The mechanism of plantar unloading in total contact casts: implications for design and clinical use

Although the total contact cast (TCC) has been shown to be an extremely effective treatment for the healing of plantar ulcers in diabetic patients, little is known about the biomechanics of its action. In this study, plantar pressure and ground reaction force measurements were obtained from over 750 foot contacts as five subjects with known elevated plantar forefoot pressures walked barefoot, in a padded cast shoe, and a TCC. Peak plantar pressures in the forefoot were markedly reduced in the cast compared with both barefoot and shoe walking (reductions of 75% and 86% respectively, P < 0.05). Peak plantar pressures in the heel were not, however, significantly different between the shoe and the TCC, and the longer duration of heel loading resulted in an impulse that was more than twice as great in the cast compared with the shoe (P < 0.05). An analysis of load distribution indicated that the mechanisms by which the TCC achieves forefoot unloading are (1) transfer of approximately 30% of the load from the leg directly to the cast wall, (2) greater proportionate load sharing by the heel, and (3) removal of a load-bearing surface from the metatarsal heads because of the "cavity" created by the soft foam covering the forefoot. These results point out some of the "essential design features" of the TCC (which are different from what had been previously supposed), support the use of the TCC for healing plantar ulcers in the forefoot, but raise questions about its utility in the healing of plantar ulcers on the heel.     

Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. I. Invariants and validation of electron microscopy models

Solutions of selectively deuterated 70 S Escherichia coli ribosomes and of free 30 S and 50 S subunits were studied by neutron scattering using contrast variation. The integrity of the partially deuterated particles was controlled by parallel X-ray measurements. Integral parameters of the entire ribosome, of its subunits and of the protein and rRNA moieties were evaluated. The data allow an experimental validation of the two most recent electron microscopy reconstructions of the 70 S ribosome presented by the groups of J. Frank (Albany) and of M. van Heel & R. Brimacombe (Berlin). For each reconstruction, integral parameters and theoretical scattering curves from the 70 S and its subunits were calculated and compared with the experimental data. Although neither of the two models yields a comprehensive agreement with the experimental data, Frank's model provides a better fit. For the 50 S subunit of van Heel & Brimacombe's model the fit with the experimental data improves significantly when the internal channels and tunnels are filled up. The poorer fit of the latter model is thus caused by its "sponge"-like structure which may partly be due to an enhancement of high frequency contributions in some of the steps of the three-dimensional image reconstruction. It seems therefore unlikely that the ribosome has a "sponge"-like structure with a pronounced network of channels.     

Evaluation of extracellular lipid peroxidation in brain cortex of anaesthetized rats by microdialysis perfusion and high-performance liquid chromatography with fluorimetric detection

OBJECTIVE: In the context of the need to develop practical outcome measures, the present study aimed to assess the sensitivity of the Life Skills Profile (LSP) in terms of differences between hospital-based and community-based clients, and to assess the sensitivity of the LSP to changes over time. In this way, criteria could be established whereby the LSP could be used to determine appropriate changes in locus of care, both in terms of the "cut-off' for hospital-based and community-based tenure, and the level of "clinically significant change' in functioning. METHOD: The LSP was administered at 3-monthly intervals to 200 clients of an area public mental health service with serious mental illness over a 21-month period. Locus of care (hospital or community) was noted at each administration. RESULTS: Clients in the community scored significantly better than those in hospital, however there was a great deal of overlap. Using hospital or community tenure as the variable of interest, a measure of reliable and clinically significant change over a 3-month period based on the LSP was developed. A total LSP score of 116.5 or above best discriminated clients in the community from those in hospital, and a difference of 18 points or more in two LSP obtained 3 months apart was unlikely to have arisen by chance. A simple, two-part criterion of significant change based on these results showed 89% accuracy in matching transition (or lack of transition) between hospital and community with changes in LSP scores. CONCLUSIONS: The results need to be understood within the methodological limitations of the present study. The findings provide users of the LSP with guidelines for the interpretation of repeat assessments. This may encourage more services to use formal reassessment methods to monitor the progress of their clients.     

De-novo reversible stenoses in tortuous arteries during coronary angioplasty due to the accordion effect. A clinical case and review of the literature

During the performance of PTCA, the operator must be able to differentiate true complications from pseudocomplications. Mechanical coronary shortening and vessel wall invagination due to accordion effect, "pseudo-transection", dissection, coronary spasm, and localized thrombosis are sources of iatrogenic obstruction during angioplasty. We report a case in which straightening of a right tortuous coronary artery during angioplasty produced an iatrogenic lesion that has a typical invaginate appearance. Conservative management is indicated in the absence of definitive angiographic aspect of vessel trauma, because they disappear after withdrawal of angioplasty equipment or adequate management of the guidewire.     

Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer

The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer.     

Euphorigenic doses of cocaine reduce [123I]beta-CIT SPECT measures of dopamine transporter availability in human cocaine addicts

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [123I]beta-CIT ([123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n = 6) were injected with [123I]beta-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28 +/- 0.03 and 0.56 +/- 0.07 mg/kg) produced significant (P < 0.0005) reductions in the specific to non-specific equilibrium partition coefficient, V3" (6 +/- 6 and 17 +/- 3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED50) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.     

Reliability of potential clinical measures of muscle tone in the elbows of patients after stroke

In order to establish a genotype-phenotype relationship, we have identified both mutant phenylalanine hydroxylase (PAH) genes in 108 phenylketonuria (PKU) patients (27 different alleles, 54 different genotypes). One major group of patients with very high pretreatment phenylalanine values ("classical" PKU) exclusively comprised homozygotes of the PKU mutations I65T, G272X, F299C, Y356X, R408W, IVS12nt1, and compound heterozygotes of various combinations of these alleles with G46S, R261Q, R252W, A259T, R158Q, D143G, R243X, E280K, or Y204C. A second major group of patients with lower phenylalanine values ("mild" PKU) comprised mutations A300S, R408Q, Y414C in various compound heterozygous states, and R261Q, R408Q, Y414C in homozygotes. The phenylalanine values in these groups were non-overlapping. In addition, a smaller group of patients formed the transition between the two main groups. In sib pairs 4 of 15 had discordant pretreatment phenylalanine values. Conclusion: Our results are consistent with the view that allelic heterogeneity at the PAH locus dominates the biochemical phenotype in PKU and that genotype information is able to predict the metabolic phenotype in PKU patients.     

Selegiline and lymphocyte superoxide dismutase activities in Parkinson''s disease

Health care: public, private or both? In Great Britain, about 13% of the population is covered by private health insurance, and everyone else is served by the public health care system known as the National Health Service, or NHS. Caroline Richmond, who examined the impact of private medical practice in Britain, says people become private patients for one compelling reason: to avoid the NHS's notoriously long waiting lists for surgery. According to Professor Alan Maynard, a health care researcher, the mainstays of the private sector are the "three h's" --hips, hernias and hemorrhoids-- along with some elective surgery, particularly in gynecology and opthalmology. Another small sector focuses on fertility regulation and cosmetic surgery. Although the levels are not monitored closely, physician consultants are not permitted to earn more than 10% of their income from private practice.     

Development of the cocaine relapse interview: an initial report

Although fine-grained analyses of circumstances surrounding relapses have been conducted with alcoholics, smokers and opiate users, there is comparatively little information about the relapse process in cocaine abusers. The Cocaine Relapse Interview (CRI) is a structured interview that gathers information on the onset, course and termination of cocaine relapse episodes. This article describes the development of the CRI and presents initial data on its reliability and validity. Sections of the CRI assess experiences on the day of the relapse, experiences during the week prior to the relapse, attributions for the relapse, experiences following initial use of cocaine and factors in terminating the relapse. Most of the subscales in each section of the CRI had adequate internal consistency and test-retest reliabilities. Validity studies indicated that most of the subscales that assess experiences prior to relapse differentiated relapsers from two control groups of non-relapsers, and that several subscales and individual items from the sections that assess experiences following initial use and factors in termination differentiated "lapsers" from "relapsers". Limitations of the CRI and recommendations for its use were also discussed.     

Activation of host cell protein kinase C by enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli (EPEC) consists of a group of diarrhea-producing E. coli strains, common in developing countries, which do not produce classical toxins and are not truly invasive. EPEC strains adhere to mammalian cells in an intimate fashion, trigger a localized increase in intracellular calcium levels, and elevate inositol phosphate production. We hypothesized that these mediators could activate host cell protein kinase C (PKC) and tested this idea in vitro with two cultured human cell lines, HeLa cells and T84 cells. Using a recently described subculturing protocol to "induce" or accelerate EPEC adherence, we infected the cells with EPEC at a multiplicity of infection of approximately 100:1 for 30 to 60 min. Under these conditions, EPEC E2348 increased membrane-bound PKC activity 1.5- to 2.3-fold in HeLa cells and T84 cells, respectively. The increase in membrane-bound PKC activity was accompanied by a decrease in cytosolic PKC activity in EPEC-infected HeLa cells. Nonadherent laboratory E. coli strains such as HB101 and H.S. failed to trigger any consistent change in PKC production, similar to the nonadherent mutant strains derived from E2348, JPN15 (plasmid cured) and CVD206 (eaeA). In addition, immunoblots performed on extracts of T84 cells with a monoclonal antibody against PKC-alpha showed an increased PKC content in membranes of EPEC-infected cells. Finally, EPEC-infected T84 cells showed a 60% increase in responsiveness to the E. coli heat-stable toxin. We conclude that mediators produced in response to EPEC adherence activate PKC in intestinal and nonintestinal cells.