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Biomedical subjects

D E Robinson

Publications and source records attributed to D E Robinson.

At least 19 recordsLinked to original sources

Ankle arthrodesis and its relationship to ipsilateral arthritis of the hind- and mid-foot.

It has been suggested that arthrodesis of the ankle leads to osteoarthritis of the joints of the ipsilateral hind- and midfoot. We believe these studies overlooked the presence of osteoarthritic changes in these joints before the arthrodesis. We reviewed the pre-operative radiographs of 70 patients with osteoarthritis of the ankle who underwent 71 ankle arthrodeses (one was bilateral). The talonavicular, calcaneocuboid, subtalar and naviculocuneiform joints were given an osteoarthritis score according to Kellgren and Lawrence. The mean age at operation was 54.9 years and the most common indication was for post-traumatic osteoarthritis (52 cases). A total of 68 patients showed pre-existing arthritis in either the hind- or mid-foot, with the subtalar joint the most commonly affected. Ipsilateral hind- and mid-foot arthritis is almost universally present in patients with arthritis of the ankle requiring arthrodesis. The presence of such changes may not be a consequence of this arthrodesis.

Adult↗

Arthroscopic ankle arthrodesis.

We reviewed 116 patients who underwent 118 arthroscopic ankle arthrodeses. The mean age at operation was 57 years, 2 months (20 to 86 years). The indication for operation was post-traumatic osteoarthritis in 67, primary osteoarthritis in 36, inflammatory arthropathy in 13 and avascular necrosis in two. The mean follow-up was 65 months (18 to 144). Nine patients (10 ankles) died before final review and three were lost to follow-up, leaving 104 patients (105 ankles) who were assessed by a standard telephone interview. The preoperative talocrural deformity was between 22 degrees valgus and 28 degrees varus, 94 cases were within 10 degrees varus/valgus. The mean time to union was 12 weeks (6 to 20). Nonunion occurred in nine cases (7.6%). Other complications included 22 cases requiring removal of a screw for prominence, three superficial infections, two deep vein thromboses/pulmonary emboli, one revision of fixation, one stress fracture and one deep infection. Six patients had a subtalar fusion at a mean of 48 months after ankle fusion. There were 48 patients with excellent, 35 with good, 10 with fair and 11 with poor clinical results.

Adult↗

Arthroscopic treatment of osteochondral lesions of the talus.

We reviewed, retrospectively, 65 patients who had undergone arthroscopic treatment for osteochondral lesions of the talus. The 46 men and 19 women with a mean age at operation of 34.25 years, were followed up for a mean of 3.5 years. The medial aspect was affected in 45 patients and the lateral aspect in 20. All the lateral lesions and 35 (75%) of the medial lesions were traumatic in origin. Medial lesions presented later than lateral lesions (3 v 1.5 years) and had a much greater incidence of cystic change (46% v 8%). At follow-up, 34 patients had achieved a good result, and 17 and 14 fair and poor results, respectively. Of the 14 poor results, 13 involved medial lesions. Cystic lesions had a poor outcome in 53% of patients. Excision and curettage led to better results than excision and drilling of the base. Further arthroscopic surgery for patients with a poor result was disappointing. There was no association between outcome and the patient's age.

Adolescent↗

Femoral impaction grafting in revision hip arthroplasty with irradiated bone.

We evaluated the results of femoral impaction grafting with the Exeter stem (Stryker Howmedica Osteonics, Newbury, UK) and irradiated bone-graft. We followed 57 hips for an average of 27 months. Endo-Klinik grading showed 8 grade 1, 22 grade 2, and 27 grade 3 hips. Radiographic analysis revealed cortical repair in 34% and graft incorporation in 39% but no evidence of trabecular remodeling. Moderate subsidence (5-10 mm) occurred in 7 patients (12.5%), and massive subsidence (>10 mm) occurred in 4 patients (7%). Complications included 6 dislocations, 3 periprosthetic fractures, and 2 stem revisions. Impaction grafting with the Exeter system produces satisfactory results for most patients, but a few hips perform poorly, and the reasons for this are unclear. We have concerns about irradiated bone-graft because the characteristic changes of graft remodeling are not seen.

Adult↗

Toxicity, bioaccumulation and tissue partitioning of dieldrin by the shrimp, Macrobrachium faustinum de Sassure, in fresh and brackish waters of Jamaica.

The 2-week no observed effect (NOEC) and lowest observed effect (LOEC) concentrations of dieldrin were determined for Macrobrachium faustinum de Sassure in fresh and brackish waters. LOEC1,10,50,95 values in fresh water were 0.001, 0.003, 0.011 and 0.058 microg l(-1), respectively, and in brackish water, 0.00006, 0.00027, 0.00165, and 0.0172 microg l(-1), respectively. The 96-hr LC10, LC50 and LC95 values were 0.029, 0.123 and 0.771 microg l(-1), respectively. It is proposed that NOEC and LOEC be redefined to take into account the percentage of individuals affected, the severity of symptoms and the recovery of poisoned individuals. Two new terms are proposed--Median Observable Effect Concentration (MOEC) for pronounced toxic symptoms in most individuals but mortality in <50%, and Pronounced Observed Effect Concentration (POEC), which inflicts mortality in >50% individuals. Bioaccumulation of dieldrin by M. faustinum from surrounding fresh and brackish waters were rapid and fairly uniform for the first 48 h when the bioconcentration equilibrium (14.4 +/- 0.42 ng g(-1) at 0.001 microg l(-1) and 42.5 +/- 1.72 ng g(-1) at 0.01 phi g l(-1)) was achieved. Relative partitioning of residues (ng g(-1) wet wt.), after 24h exposure to 0.001 microg l(-1) of dieldrin in fresh water, in the different tissues was hepatopancreas > gonads > gills > large claws > muscle and exoskeleton. Shrimp which had accumulated 10.5 +/- 0.52 ng g(-1) dieldrin in fresh and brackish water, eliminated only about 52% of the residues after eight days in uncontaminated water.

Animals↗

Iliopsoas hematoma with femoral neuropathy presenting a diagnostic dilemma after spinal decompression.

STUDY DESIGN: Case report of an iliopsoas hematoma with femoral neuropathy appearing 8 weeks after a posterior spinal decompression procedure. OBJECTIVES: To describe a potential complication and differential diagnosis for nerve root symptoms following spinal decompression. SUMMARY OF BACKGROUND DATA: Iliopsoas hematoma is usually a complication of anticoagulation, hemophilia, or trauma. It has not been described previously as a complication of posterior spinal decompression. Femoral neuropathy results from compression within the iliopsoas compartment. METHODS: A 53-year-old woman reported pain in the right side of her groin and an increasing fixed flexion deformity of the right hip 8 weeks after a posterior, midline, spinal decompression. A femoral neuropathy later developed. Magnetic resonance imaging and computed tomography were performed. RESULTS: Imaging studies demonstrated a diffusely enlarged iliopsoas. Exploration revealed a large hematoma, which was evacuated. The compartment was fully decompressed with resolution of the nerve root symptoms within 48 hours. CONCLUSIONS: Iliopsoas pathology is a rare cause of nerve root symptoms and presented diagnostic difficulties after an apparently successful spinal decompression.

Compartment Syndromes↗

Inactivation of protein farnesyltransferase by active-site-targeted dicarbonyl compounds.

Upon farnesylation by protein farnesyltransferase (FTase), key proteins become compartmentalized in cells. For example, cell membrane localization is essential for the mitogenic role of mutant Ras protein, which acts as a switch for cancer cell proliferation. We report that alpha-dicarbonyl compounds derived from the isoprenoid skeleton or other hydrophobic groups potently obstruct farnesylation of a Ras model peptide by human recombinant FTase in vitro. A geranyl-derived isoprenoid diketone, 5,9-dimethyl-8-decene-2,3-dione, at 17 microM caused a 62% reduction in FTase activity after 30 minutes. A farnesyl-derived isoprenoid diketone, 5,9,13-trimethyl-8,12-tetradecadiene-2,3-dione, at 93 microM caused a 94% reduction after 30 minutes. Other dicarbonyl compounds found to be effective against FTase in vitro were (+/-)-6-(camphorquinone-10-sulfonamido)-hexanoic acid, 4,4'-biphenyldiglyoxaldehyde, dehydroascorbic acid 6-palmitate, 2-oxododecanal, and phenylglyoxal. Higher concentrations of the alpha-dicarbonyl compound resulted in more rapid and more extensive inactivation. These findings demonstrate that alpha-dicarbonyl compounds targeted to FTase interfere with protein farnesylation in vitro and may lead to derivatives that have utility as chemotherapeutic agents.

Alkenes↗

Background and framework for ILSI's collaborative evaluation program on alternative models for carcinogenicity assessment. International Life Sciences Institute.

The willingness of the agencies involved in the regulation of pharmaceuticals to accept data from newly proposed models for carcinogenicity testing (eg, transgenic animals, neonatal rodent models, initiation-promotion models) has stimulated international interest in gaining experience and a greater understanding of the strengths and limitations of the specific models. Over a 4-year period, the International Life Sciences Institute (ILSI) Health and Environmental Science Institute (HESI) has coordinated a large-scale collaborative research program to help to better characterize the responsiveness of several models proposed for use in carcinogenicity assessment. The overall objective of this partnership among industry, government, and academic scientists was to evaluate the ability of these new models to provide useful information for human cancer risk assessment. This research program reflected a commitment of nearly US$35 million by over 50 industrial, govemment, and academic laboratories from the United States, Europe, and Japan. Evaluation of the models required the development of standardized protocols to allow reproducibility and comparability of data obtained across multiple laboratories. Test compounds were selected on the basis of mechanistically meaningful carcinogenic activity or noncarcinogenicity in the rodent bioassay as well as humans. Criteria were established for dose selection, pathology review, quality control, and for evaluation of study outcome. The database from these studies represents an important contribution to the future application of new models for human cancer risk assessment. Beyond the data, the collaborative process by which the models were evaluated may also represent a prototype for assessing new methods in the future.

Academies and Institutes↗

Convenient preparation of O-linked polymer-bound N-substituted hydroxylamines, intermediates for synthesis of N-substituted hydroxamic acids.

[reaction: see text] An efficient procedure for preparation of O-linked polymer-bound N-substituted hydroxylamines by reduction of resin-bound oximes with borane.pyridine complex in the presence of dichloroacetic acid is reported. Other reducing systems commonly used for imine or oxime reduction were ineffective, including borane.pyridine in the presence of acetic acid. Oximes derived from a variety of aromatic and aliphatic aldehydes and ketones were successfully reduced. The N-substituted products were acylated and cleaved from resin to afford N-substituted hydroxamic acids.

Journal Article↗

Elastography--the movement begins.

The advent of real-time ultrasound in the 1970s, together with a growing interest in tissue characterization, led to a number of investigators using the nature of tissue motion to distinguish healthy from diseased tissue. Our group at the (then) Ultrasonics Institute demonstrated the use of phase methods for detecting very small tissue motions, using natural stimuli. The method could also be applied in the lag (autocorrelation) domain to directly measure the amount of deformation to high accuracy. This method was also applied to measuring the amount of dilatation of blood vessels using both conventional and intravascular ultrasound. A basic limitation of these techniques was the poor spatial resolution, and quasistatic methods soon replaced this method of measuring tissue deformation. However, a new way of assessing the health of tissues had been established.

Blood Vessels↗

Lessons learned in applying the U.S. EPA proposed cancer guidelines to specific compounds.

An expert panel was convened to evaluate the U.S. Environmental Protection Agency's "Proposed Guidelines for Carcinogen Risk Assessment" through their application to data sets for chloroform (CHCl3) and dichloroacetic acid (DCA). The panel also commented on perceived strengths and limitations encountered in applying the guidelines to these specific compounds. This latter aspect of the panel's activities is the focus of this perspective. The panel was very enthusiastic about the evolution of these proposed guidelines, which represent a major step forward from earlier EPA guidance on cancer-risk assessment. These new guidelines provide the latitude to consider diverse scientific data and allow considerable flexibility in dose-response assessments, depending on the chemical's mode of action. They serve as a very useful template for incorporating state-of-the-art science into carcinogen risk assessments. In addition, the new guidelines promote harmonization of methodologies for cancer- and noncancer-risk assessments. While new guidance on the qualitative decisions ensuing from the determination of mode of action is relatively straightforward, the description of the quantitative implementation of various risk-assessment options requires additional development. Specific areas needing clarification include: (1) the decision criteria for judging the adequacy of the weight of evidence for any particular mode of action; (2) the role of mode of action in guiding development of toxicokinetic, biologically based or case-specific models; (3) the manner in which mode of action and other technical considerations provide guidance on margin-of-exposure calculations; (4) the relative roles of the risk manager versus the risk assessor in evaluating the margin of exposure; and (5 ) the influence of mode of action in harmonizing cancer and noncancer risk assessment methodologies. These points are elaborated as recommendations for improvements to any revisions. In general, the incorporation of examples of quantitative assessments for specific chemicals would strengthen the guidelines. Clearly, any revisions should retain the emphasis present in these draft guidelines on flexibility in the use of scientific information with individual compounds, while simultaneously improving the description of the processes by which these mode-of-action data are organized and interpreted.

Animals↗

Fate and transport of ethoprophos in the Jamaican environment.

The hydrolytic half lives of ethoprophos in distilled, river, brackish and open sea water were 25, 133, 65 and 81 days, respectively. Under laboratory conditions, volatilisation of the residues after 12 h was 1.4-3.6, 2.3-4.5 and 6.5-20.2% from a sandy loam soil with 1, 10 and 20% moisture levels, respectively. Photolysis in soil was significantly faster (P < 0.05) in direct sunlight (T1/2 of 4.7 days) than in the shade (T1/2 of 12.3 days). The microbial degradation of ethoprophos was more than two-fold faster in unsterile soil (T1/2 of 10.9 days) than in sterile soil (T1/2 of 28.8 days). The runoff of ethoprophos from unweeded plantation soil at 23 degrees slope was significantly (P = 0.015) less than at 38 degrees slope; the amounts lost after 9 weeks and 27.5 mm of rainfall were 89.4 and 91.2%, respectively, of the applied amount from the two respective slopes. In the weeded plots, 93.6 and 92.4% of the applied insecticide were lost from 23 degrees and 38 degrees slopes, respectively. Under laboratory conditions, between 67.0 and 85.1% of ethoprophos leached through the soil columns. Under field conditions, after 9 weeks and 25 mm of rainfall, only 2.8 and 2.0% residues were recovered at a depth of 10-15 cm from unweeded and weeded slopes, respectively at 23 degrees slope, and 2.2 and 1.9% from the two respective plots at 38 degrees slope.

Biodegradation, Environmental↗

Tetrahydropapaveroline injected in the ventral tegmental area shifts dopamine efflux differentially in the shell and core of nucleus accumbens in high-ethanol-preferring (HEP) rats.

Since the 1970s tetrahydropapaveroline (THP) and other tetrahydroisoquinoline alkaloids have been implicated in the etiology of alcoholism. When injected into the cerebral ventricle or at specific sites in the mesolimbic system such as the ventral tegmental area (VTA), THP evokes spontaneous and intense intake of alcohol in the nondrinking animal. Further, THP evokes the extracellular efflux of dopamine in the nucleus accumbens (NAC), which comprises, in part, the postulated alcohol drinking "circuit" of neurons. The purpose of this study was to characterize the action of a THP reactive structure, the VTA, on the activity of dopamine and its metabolism in the NAC. In the anesthetized high-ethanol-preferring (HEP) rat, artificial CSF was perfused for 10 min at a rate of 10 microl per min specifically in either the core or shell of the NAC. A microbore push-pull cannula system was selected over a microdialysis probe because of its superior recovery of neurotransmitters and tip exposure of less than 1.0 mm. After a series of 5-min perfusions, a single microinjection of 5.0 microg/microl of THP was made in the ipsilateral VTA while the NAC was perfused simultaneously. Sequential samples of the NAC perfusate were assayed by an HPLC coulometric system to quantitate the concentrations of dopamine and its metabolites, DOPAC and HVA, as well as the 5-HT metabolite, 5-HIAA. The results showed that THP injected in the VTA caused a significant increase by 94 +/- 23% in the efflux of dopamine from the core of the NAC. Conversely, the THP injected identically in the VTA suppressed the efflux of dopamine within the shell of the NAC by 51 +/- 10%. The levels of DOPAC, HVA and 5-HIAA within the core and shell of the NAC generally paralleled the increase and decrease in efflux, respectively, of dopamine. CSF control injections in the VTA as well as injections outside of the VTA failed to alter dopamine or metabolite activity in the NAC. These results demonstrate that the presence of THP in the VTA alters directly the function of the pathway of mesolimbic neurons generally and the dopaminergic system specifically. That such a perturbation could account for the induction of alcohol preference is proposed in relation to a reinforcing mechanism involving opioidergic and dopaminergic elements.

Alcoholism↗

The role of certification in the buyer/planner position: a case study at Harley-Davidson Motor Company.

The use of buyer/planners may becoming more popular. If they are, the reason is probably that many companies are integrating materiel management skill sets as a way of increasing the effectiveness of their supply chains. Harley-Davidson recently created a supply management function composed of buyer/planners. This article describes the method it used to achieve the transition, the training plan it implemented to support the process, and the role management played in achieving success.

Administrative Personnel↗

Genetics of alcoholism: rapid development of a new high-ethanol-preferring (HEP) strain of female and male rats.

A genetically based animal model of alcoholism has been developed in a relatively short period of 3 years. The new strain is characterized by an intense preference for ethanol over water as well as unique behavioral, neurochemical and other attributes. This new strain, termed high-ethanol-preferring (HEP) rats, was derived initially from selective cross-breeding of a variant strain of female Harlan Sprague-Dawley (SD) rats with the outbred Wistar line of male ethanol-preferring (P) rats. In this study, drinking patterns of both genders were obtained over 10 days by presenting water and ethanol in concentrations ranging from 3% to 30%. To expedite the development of the new strain, only three to five female and male rats served as breeders, which were chosen from all litters on the basis of their maximum g/kg intake integrated with proportion of ethanol to total fluid values. Profiles of intake of preferred concentrations of ethanol were obtained over 24 h of unlimited access as well as during 2-h intervals of limited access to ethanol. Levels of blood ethanol were measured in both female and male HEP animals during bouts of ethanol drinking in the limited access paradigm. By the sixth generation of HEP rats, ethanol consumption of the females often exceeded that of any other rat genetically bred to drink ethanol (e.g., at a concentration of 15.7%, 10.3 g/kg per day). Seven additional characteristics are notable: 1) the HEP rats prefer ethanol in the presence of a nutritious chocolate drink or nonnutrient sweetened solution (aspartame); 2) high levels of blood ethanol are associated with their drinking; 3) females drink significantly greater g/kg amounts of ethanol than HEP males and prefer a higher percent concentration of ethanol; 4) the drinking of ethanol by the female HEP animals does not fluctuate during the estrous cycle; 5) neurochemical assays show differential profiles of 5-HT, dopamine, and their metabolites in different regions of the brain; 6) measures of activity using the elevated plus maze, open field, and cork gnawing reveal differences between genders of HEP rats and SD rats; and 7) the HEP animals are without phenotypically expressed abnormalities. Finally, one cardinal principle derived from this study revealed that the breeding strategy to develop high-ethanol-drinking rats centers on the use of multiple solutions of ethanol whereby the intakes of ethanol in concentration of 9% through 20% dictate the ultimate selection of breeding pairs over successive F generations. Further, it is concluded that because of an intense rise in ethanol drinking of the F1 generation of female HEP rats well above that of the parental SD female breeders, the complex genotypic characteristic of the male P rat is predominantly responsible for evoking ethanol drinking in female offspring.

Alcohol Drinking↗

Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans?

The purpose of the workshop "Do Peroxisome Proliferating Compounds Pose a Hepatocarcinogenic Hazard to Humans?" was to provide a review of the current state of the science on the relationship between peroxisome proliferation and hepatocarcinogenesis. There has been much debate regarding the mechanism by which peroxisome proliferators may induce liver tumors in rats and mice and whether these events occur in humans. A primary goal of the workshop was to determine where consensus might be reached regarding the interpretation of these data relative to the assessment of potential human risks. A core set of biochemical and cellular events has been identified in the rodent strains that are susceptible to the hepatocarcinogenic effects of peroxisome proliferators, including peroxisome proliferation, increases in fatty acyl-CoA oxidase levels, microsomal fatty acid oxidation, excess production of hydrogen peroxide, increases in rates of cell proliferation, and expression and activation of the alpha subtype of the peroxisome proliferator-activated receptor (PPAR-alpha). Such effects have not been identified clinically in liver biopsies from humans exposed to peroxisome proliferators or in in vitro studies with human hepatocytes, although PPAR-alpha is expressed at a very low level in human liver. Consensus was reached regarding the significant intermediary roles of cell proliferation and PPAR-alpha receptor expression and activation in tumor formation. Information considered necessary for characterizing a compound as a peroxisome proliferating hepatocarcinogen include hepatomegaly, enhanced cell proliferation, and an increase in hepatic acyl-CoA oxidase and/or palmitoyl-CoA oxidation levels. Given the lack of genotoxic potential of most peroxisome proliferating agents, and since humans appear likely to be refractive or insensitive to the tumorigenic response, risk assessments based on tumor data may not be appropriate. However, nontumor data on intermediate endpoints would provide appropriate toxicological endpoints to determine a point of departure such as the LED10 or NOAEL which would be the basis for a margin-of-exposure (MOE) risk assessment approach. Pertinent factors to be considered in the MOE evaluation would include the slope of the dose-response curve at the point of departure, the background exposure levels, and variability in the human response.

Animals↗