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Biomedical subjects

D Wilkie

Publications and source records attributed to D Wilkie.

At least 19 recordsLinked to original sources

Translabial sonography of vaginal fibroids: report of 2 cases and review of the literature.

OBJECTIVE: To determine the role of translabial sonography in the diagnosis of vaginal fibroids. METHODS: Two women with vaginal masses of undetermined origin were examined by various imaging procedures, including translabial sonography. RESULTS: Initial examinations, which included transabdominal sonography, cystoscopy, and cystourethrography, yielded inconclusive findings. Translabial sonography, however, suggested isolated vaginal leiomyomas in both patients, and in both the diagnosis was confirmed histologically after surgery. CONCLUSIONS: Translabial sonography should be considered as an adjunct to transabdominal and transvaginal sonography for patients with suspected vaginal fibroids.

Adult↗

Valuation of consumption and sale of forest goods from a Central American rain forest

Researchers recognize that society needs accurate and comprehensive estimates of the economic value of rain forests to assess conservation and management options. Valuation of forests can help us to decide whether to implement policies that reconcile the value different groups attach to forests. Here we have measured the value of the rain forest to local populations by monitoring the foods, construction and craft materials, and medicines consumed or sold from the forest by 32 Indian households in two villages in Honduras over 2.5 years. We have directly measured the detailed, comprehensive consumption patterns of rain forest products by an indigenous population and the value of that consumption in local markets. The combined value of consumption and sale of forest goods ranged from US$17.79 to US$23.72 per hectare per year, at the lower end of previous estimates (between US$49 and US$1,089 (mean US$347) per hectare per year). Although outsiders value the rain forest for its high-use and non-use values, local people receive a small share of the total value. Unless rural people are paid for the non-local values of rain forests, they may be easily persuaded to deforest.

Journal Article↗

Mutuality and solidarity: assessing risks and sharing losses.

Mutuality is the principle of private, commercial insurance; individuals enter the pool for sharing losses, and pay according to the best estimate of the risk they bring with them. Solidarity is the sharing of losses with payment according to some other scheme; this is the principle of state social insurance; essential features of solidarity are comprehensiveness and compulsion. Private insurance is subject to the uberrima fides principle, or utmost good faith; each side declares all it knows about the risk. The Disability Discrimination Act requires insurers to justify disability discrimination on the basis of relevant information, acturial, statistical or medical, on which it is reasonable to rely. It could be very damaging to private insurance to abandon uberrima fides. However, although some genetic information is clearly useful to underwriters, other information may be so general as to be of little use. The way in which mortality rates are assessed is also explained.

Cost Sharing↗

Morphological and structural characteristics of the proximal femur in human and rat.

Because the ovariectomized rat model of postmenopausal osteoporosis is the most commonly used small animal model to investigate consequences of bone loss on bone structure and strength, or to assess benefits of the various therapeutic strategies to improve bone mass and strength, the attempt was made to compare histoanatomical and structural characteristics of the femoral neck between human and rat models. In addition to different biomechanics, there is a significant difference in gross- and microanatomy of the proximal femur between humans and rats. Percent of the cortical bone component is much higher in rats (72.5%) relative to humans (12.5%). Also, cortical bone at the femoral neck in rats is evenly distributed, whereas in humans there is a considerable difference in the amount of the cortical bone between the superior half of the femoral neck with cortical thickness being only 0.3 mm, and the inferior half of the neck having 6-mm-thick cortex. Humans have far more cancellous bone at the femoral neck (22.7% average) relative to rats (6.8%). In addition, cancellous bone at the femoral neck in humans is unevenly distributed between the bone center and its periphery. Human samples exhibited striking differences in the cancellous bone structure between weight-bearing and tensile trabecular groups exhibiting clear trabecular orientation consisting of plates and rods, and trabeculae around the neutral bone axis with little mechanical activity exhibiting rod-like trabeculae only. Although humans and rats have a periosteum covering the femoral neck, and each lacks the muscular attachment at intracapsular portions of the femoral neck, rats, in contrast to humans, have the ability to quickly adapt cortical thickness and increase inertia to meet mechanical needs via modeling-dependent periosteal apposition.

Aged↗

High-pressure replica technique for in vitro imaging of pore morphologies in teeth.

The presence of a natural pore morphology is an essential factor in chemical and mechanical stability of teeth. Common histological methods give only an insufficient picture of the three-dimensional pore distribution in sound or carious teeth. This paper describes a new technique to obtain complete images of the pore structure in teeth or other biological hard tissues. Whole extracted human teeth from orthodontic therapy are mechanically cleaned and organic remnants removed chemically. After being (partly) dried, the teeth are penetrated by a freshly prepared and colored (rhodamine B dye) two-component epoxy resin. The resin is pressed into the pores and cavities of the teeth with pressures of up to 2000 bar in a high-pressure vessel by means of a manually driven piston screw pump for pressure generation. The resin fills all hollow spaces of the tooth down to sizes below 0.1 micron. The pulp and the root canals are cast in massive forms of the hardened epoxy resin, giving an exact replica of the natural structure. The penetrated samples in the form of whole, intact teeth are investigated microscopically so that the pore morphology of the tooth surface, including carious defects, can be examined. The structure of the pores extending into the interior of the tooth can be made visible by dissolution of the hard tissue--for example, in acid solutions. Micro-cavities filled with the resin are observed in thin, ground, and polished cross- and longitudinal sections cut from the teeth. The colored resin induces a high contrast to the dental apatite material. In fluorescence microscopy, only the resin structures are visible.

Animals↗

Mitochondrial activity and cytotoxicity of vitamin A (retinol) in yeast and human cell cultures. Protective effect of antioxidants.

Vitamin A inhibited the growth of yeast and human cells in a dose-dependent but selective manner in cultures utilizing a non-fermentable carbon and energy source. At sub-inhibitory concentrations in yeast cultures (approximately 100 micrograms/mL), the vitamin had a stimulatory effect on the mitochondrial system, foreshortening the lag phase in the adaptation to non-fermentable substrate. At inhibitory concentrations, vitamin A depressed mitochondrial protein synthesis relative to cytoplasmic protein synthesis and induced the mitochondrial mutation petite but had little or no mutagenicity with respect to nuclear genes at the concentrations used. The vitamin showed a dose-dependent cytotoxicity (lethality) in both yeast and human cells. All of these deleterious effects were overcome to a large extent by the presence of antioxidants implicating free-radical metabolites in much of the toxicity.

Antioxidants↗

Effect of antioxidants on the mitochondrial activity and toxicity of the cancer drug methylglyoxal bis (guanylhydrazone) in yeast and mammalian cells.

Mitochondria of yeast cells were primary targets of methylglyoxal bis (guanylhydrazone) (MGBG) from the following criteria: (1) selective inhibition of growth of cells utilizing a non-fermentable energy source, (2) inhibition of mitochondrial protein synthesis compared with cytosolic protein synthesis and (3) selective mutagenesis of the mitochondrial genome compared with nuclear mutagenesis. Evidence of primary antimitochondrial activity of MGBG in mammalian cells was provided by greater potency of the drug in guinea pig keratinocyte cultures utilizing glutamine as carbon and energy source compared with fermentable glucose. Cell death was used as a measure of drug toxicity in both yeast and mammalian systems. The antioxidants glutathione, vitamin E and vitamin C reversed toxicity and antimitochondrial activity to a large extent implying that toxic free radical metabolites of the drug are of significance in cellular activity of MGBG.

Animals↗

Cancer pain intensity measurement: concurrent validity of three tools--finger dynamometer, pain intensity number scale, visual analogue scale.

Although the visual analogue scale (VAS) and number scales are known to be valid and sensitive measures of pain intensity, some older individuals are unable to use them. For individuals who lack the ability to use these scales, valid alternative measures of pain intensity would be useful for research and clinical practice. The purpose of this study was to examine the concurrent validity of a new measure of pain intensity, the Finger Dynamometer (FD), in a sample of 15 adults with advanced stage cancer pain. In a repeated measures correlational design each patient rated present pain intensity using the FD, a Pain Intensity Number Scale (PINS), and a VAS at four separate times. Data analyses using Kendall Correlational Coefficients indicated weak to moderate correlation between the FD and PINS (gamma = .47 to .68; p less than .01) and between the FD and VAS (gamma = .38 to .46; p less than .05) at each measurement time. Strong correlation was found between the VAS and the PINS (gamma = .77 to .89; p less than .001). Findings support the concurrent validity of the VAS and the PINS but indicate that further research is necessary to establish the psychometric properties of the FD as a measure of pain intensity in chronic pain models, such as cancer pain. Recommendations are made regarding important variables to be considered in further research with the FD.

Evaluation Studies as Topic↗

Primary mitochondrial activity of gossypol in yeast and mammalian cells.

Gossypol showed primary antimitochondrial activity in yeast cells in that the drug (1) inhibited growth of cells utilizing mitochondrial substrates as carbon and energy sources, and (2) selectively inhibited mitochondrial protein synthesis. Primary antimitochondrial activity was demonstrated in guinea-pig keratinocytes (GPK) by early arrest of growth and loss of viability in medium with glutamine (a mitochondrial substrate) as carbon and energy source compared with cells utilizing glucose. Gossypol depressed oxygen uptake directly in respiring cells. Gossypol interacted with the known antimitochondrial agents ethidium bromide and 5-fluorouracil (FU), potentiating the activity of FU but reversing that of ethidium bromide in yeast and GPK. Also, the activity of the mitochondrial inhibitor oligomycin was reversed by the presence of gossypol in yeast cells but not tested in GPK. The uptake and retention of the mitochondria-specific dye rhodamine 123 were much depressed by gossypol in GPK. Gossypol showed little or no inhibitory effects in yeast or GPK in the presence of ethanol (0.2-0.5%). The drug was not mutagenic with respect to the yeast mitochondrial system. It was tentatively suggested that mitochondrial perturbation could explain the antifertility effect of gossypol if it is assumed that mitochondria have a special role to play in spermatogenesis and sperm motility, making these tissues more sensitive to mitochondrial inhibitors than somatic cells.

Animals↗

Expression of the primary biliary cirrhosis antigens in yeast: aspects of mitochondrial control.

The mitochondria of 21 yeast strains were tested for the expression of primary biliary cirrhosis (PBC) specific antigens. The amounts of the antigens in the mitochondrial preparations varied with the strains. Genetic analysis of the strain differences in antigen expression indicated nuclear control which was complex. Those strains expressing the least amounts of antigens exhibited coagulating mitochondria in organellar preparations. Additional evidence relating expression of antigens to the physiological/structural state of mitochondria was that cells grown in the presence of the mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP), failed to produce any antigens, and that glucose repression of mitochondria suppressed antigen expression. Blockage of mitochondrial protein synthesis either through petite mutation or by culture in the presence of erythromycin decreased the content of antigens in the mitochondria but did not completely block antigen production. The presence of the PBC antigen in the mitochondria of these cells with nonfunctional mitochondrial synthesizing machinery further indicates that these antigens are cytoplasmically synthesized. Analysis of the pre- and postmitochondrial fractions of all homogenates confirmed that the antigens are not only cytoplasmically synthesized but also have an extramitochondrial location in cells, probably in the plasma membrane.

Antigens, Fungal↗

Enrichment of collagen and gelatin degrading activities in the plasma membranes of human cancer cells.

Interactions between connective tissue substrates and proteinases localized to the surface of cancer cells are implicated in cancer invasion. In this report we have compared the enrichment of collagen and gelatin degrading activities and cysteine proteinase(s) in well-characterized (enzyme markers and electron microscopy) subcellular membrane fractions isolated from human small cell lung cancer lines (NCI-H69 and NCI-H82) and the RWP-1 pancreatic cancer line. With each cell line collagenolytic, gelatinolytic, and cysteine proteinase activities were enriched 5- to 128-fold in the plasma membrane fractions with differences noted between microvilli versus smooth membrane profiles. Incubation of tumor plasma membranes with methyl-3H-labeled collagen resulted in extensive degradation of the gamma, beta, alpha 1, and alpha 2 chains, suggesting the combined action of metalloproteinases. Treatment of tumor plasma membranes with the chaotropic agent, 2 M KCl, did not diminish membrane collagen- or gelatin-degrading activity, but extensively leached out the cysteine proteinase, suggesting that the latter enzyme is not an integral membrane protein. Enzyme inhibitors specific for metalloproteinases and cysteine proteinase were used to corroborate enzymatic classification. In conclusion, we have demonstrated variations in the localization of proteinases in the plasma membrane domains of different human cancer cells.

Cell Membrane↗

Effects of haloperidol and d-amphetamine on perceived quantity of food and tones.

The hypothesis that dopamine (DA) receptor agonists and antagonists affect "hedonia" associated with natural rewards was tested, using a psychophysical procedure previously shown to be sensitive to both the sweetness of food and the motivational state of rats. Rats were first trained to discriminate between two different quantities of a rewarding stimulus by pressing one of two levers. Perceived quantity was subsequently derived from generalization trials of intermediate quantities. Haloperidol (0.03-0.083 mg/kg), a DA receptor antagonist, did not influence perceived food quantity, an indirect marker of hedonic value. On the other hand, d-amphetamine (0.25-1.0 mg/kg) affected perceived food quantity in a dose-dependent fashion, and in the same direction as occurs after increasing hunger or food sweetness. Both haloperidol and amphetamine influenced the perceived quantity of a stimulus without natural reinforcing properties (a tone), but the effect of amphetamine on the perceived quantity of this initially neutral stimulus was opposite in direction to that observed with food. These results suggest that whereas amphetamine affects hedonic processes, haloperidol does not. In addition, it seems that haloperidol probably produces its actions through effects on motor mechanisms or by interfering with the response-facilitating properties of rewards.

Animals↗

Purification of a hemolytic factor from ras oncogene transformed fibroblasts.

Transformation of NIH-3T3 fibroblasts by the Harvey murine sarcoma viral oncogene or by cultivation of fibroblasts under low serum conditions (spontaneous) resulted in the acquisition of hemolytic activity, as demonstrated by coincubation of the transformed fibroblasts with 59Fe-labeled red blood cells. The tumor Hemolytic Factor was partially purified from conditioned media produced by T-24 human bladder transformed fibroblasts by ammonium sulfate precipitation, followed by anion and gel filtration chromatography. The hemolytic factor has a molecular weight of 66,000 as documented by SDS-PAGE and is destroyed by heating to 60 degrees C.

Animals↗

Continuous infusion of spinally administered narcotics for the relief of pain due to malignant disorders.

The INFUSAID model #400 totally implantable drug delivery system was implanted in 17 patients for the continuous infusion of spinally administered preservative-free morphine sulfate. Sixteen patients had pain of malignant origin, and one patient had pain secondary to meningomyelocele. Over time, there was a consistent mean improvement in analgesia scores ranging from 50% to 70% of the control levels for 16 of the patients with cancer-related pain. This form of pain therapy was not successful in treating the benign pain of the patient with meningomyelocele. Overall, the patients with cancer were pleased with their pain therapy, experienced few complications, and reported improved quality of life. Continuous infusion of spinally administered narcotics using a totally implantable drug delivery system such as the INFUSAID model #400 is a safe, complication-free procedure for the control of cancer-related pain.

Aged↗

Effect of aspirin on mitochondrial mutagens in Saccharomyces cerevisiae.

The mitochondrial mutation petite was induced in yeast cells by ethidium bromide (EB), Adriamycin (ADR) and 4-nitroquinoline-N-oxide (NQO). In the presence of aspirin in concentrations ranging from 0.1 to 1.0 mg/ml, the mutagenicity of EB and ADR was reversed but petite induction by NQO was unaffected. At these concentrations, aspirin also reversed mitochondrial inhibition by oligomycin, a non-mutagenic inhibitor of the organellar ATPase complex. Cells grown in the presence of aspirin alone showed a significantly higher rate of oxygen uptake than untreated control cultures when the drug concentration ranged from 0.05 to 1.0 mg/ml. At concentrations of 2 mg/ml and above, aspirin inhibited mitochondrial respiration.

Aspirin↗