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Biomedical subjects

L C Clark

Publications and source records attributed to L C Clark.

At least 55 records · Page 3Linked to original sources

Evaluation of silicone gel as a long-term vitreous substitute in non-human primates.

Two preparations of silicone gels were evaluated as long-term vitreous substitutes in the vitrectomized and lensectomized eyes of primates. Both preparations were injected in liquid form and polymerized in the vitreous cavity. There was no toxic effect on the ocular structures up to 13 months after implantation. Fundus examination and fluorescein angiography were possible through the less rigid gel, whereas the preparation with higher rigidity consistently appeared cloudy.

Animals↗

Results of prenatal alcohol exposure on the dimensions and binucleation of cardiac myocytes in neonatal and weanling rats.

Sprague-Dawley rats were exposed to ethyl alcohol in utero. The effect of chronic prenatal exposure was examined by giving mature females alcohol in isocaloric liquid diets which served as the sole source of liquid and caloric intake before mating and throughout gestation. Controls consisted of females maintained on laboratory chow or an isocaloric liquid diet minus alcohol before and during gestation. The offspring were sacrificed at 21 days of age (weanlings) and the hearts dissociated enzymatically to give purified cardiac myocytes. The effects of daily acute prenatal alcohol exposure were studied by gastric intubation of alcohol to chow-fed females for the duration of pregnancy. The doses used approximated 4 and 5 shots of 80 proof liquor per day by a person weighing 150 lb. These offspring were sacrificed at 2, 6, and 21 days postnatal and cardiac myocytes prepared as above. Heart weights were determined and cardiac myocytes were analyzed for cell length, volume, cross-sectional area, and percent binucleation. Additionally, nuclear DNA content was measured in all of the 21 day offspring. Statistical analysis of the data showed no significant differences between hearts exposed to prenatal alcohol and nonexposed controls with either regimen with the exception of percent binucleation which was significantly but only slightly higher in the 6-day-old hearts. These findings are discussed in relation to anatomical heart defects found in patients with full fetal alcohol syndrome.

Aging↗

Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies.

Procedures for reporting and monitoring the accuracy of biochemical measurements are presented. They are proposed as standard reporting procedures for laboratory assays for epidemiologic and clinical-nutrition studies. The recommended procedures require identification and estimation of all major sources of variability and explanations of laboratory quality control procedures employed. Variance-components techniques are used to model the total variability and calculate a maximum percent error that provides an easily understandable measure of laboratory precision accounting for all sources of variability. This avoids ambiguities encountered when reporting an SD that may taken into account only a few of the potential sources of variability. Other proposed uses of the total-variability model include estimating precision of laboratory methods for various replication schemes and developing effective quality control-checking schemes. These procedures are demonstrated with an example of the analysis of alpha-tocopherol in human plasma by using high-performance liquid chromatography.

Analysis of Variance↗

Vitreon, a new perfluorocarbon.

We evaluated a new liquid perfluorocarbon, perfluorophenanthrene (Vitreon). This material has proven to be non-toxic in vitrectomised rabbit eyes for up to six weeks. Present investigation under FDA guidelines establishes both the safety and efficacy of Vitreon in human eyes. We used Vitreon for intraoperative hydrokinetic retinal manipulation in 15 patients. In cases of proliferative vitreoretinopathy (6), rhegmatogenous retinal detachment (5), giant retinal tear (2), retinal dialysis (1), and tractional retinal detachment (1) the retina was successfully reattached. Postoperatively two patients developed proliferative vitreoretinopathy necessitating further surgery, and one patient developed hypotony. Follow-up showed 100% reattachment rate with a mean duration of 6.3 months. Postoperative visual acuity ranges from light perception to 20/30.

Adult↗

Long-term vitreous replacement in primates with intravitreal Vitreon or Vitreon plus silicone.

Six African green monkeys (six eyes) underwent vitrectomy and vitreous replacement with Vitreon (perfluorophenanthrene) or Vitreon plus silicone. A seventh animal served as a control. Vitreon alone and in combination remained optically clear and allowed fundus examination up to 162 days. No toxic effects to the retina were detectable. Vitreon exhibited some degree of emulsification and formed some globules at 45 days postoperatively. Interestingly, Vitreon emulsification occurred at a later time (80 days) in one of the silicone plus Vitreon eyes. The combination of silicone plus Vitreon may offer the advantage of tamponading the inferior and superior retina in phakic eyes.

Animals↗

Monitoring for clusters of disease: application to leukemia incidence in upstate New York.

The authors propose a procedure for the detection of significant clusters of chronic diseases, with particular reference to cancer. The procedure allows for variations in population density and avoids the problem of "post hoc" formation of hypotheses or self-defined populations. This accounts for several of the principal problems of cluster evaluations. The techniques are practical but "computer-intensive." The procedure, termed the "cluster evaluation permutation procedure," is applied to leukemia incidence data for an Upstate New York region obtained from the New York State Cancer Registry and census files. Comparisons are made with two other recently proposed clustering methods, namely the U-statistic method of Whittemore et al. (Biometrika 1987;74:631-7) and the "geographical analysis machine" of Openshaw et al. (Lancet 1988;1:272-3). Routine examination of disease occurrence with the cluster evaluation permutation procedure would allow state health officials to prioritize case investigations and to respond in a timely and efficient manner to inquiries of reported clusters.

Cluster Analysis↗

Analysis of multi-type recurrent events in longitudinal studies; application to a skin cancer prevention trial.

We consider the statistical modeling and analysis of replicated multi-type point process data with covariates. Such data arise when heterogeneous subjects experience repeated events or failures which may be of several distinct types. The underlying processes are modeled as nonhomogeneous mixed Poisson processes with random (subject) and fixed (covariate) effects. The method of maximum likelihood is used to obtain estimates and standard errors of the failure rate parameters and regression coefficients. Score tests and likelihood ratio statistics are used for covariate selection. A graphical test of goodness of fit of the selected model is based on generalized residuals. Measures for determining the influence of an individual observation on the estimated regression coefficients and on the score test statistic are developed. An application is described to a large ongoing randomized controlled clinical trial for the efficacy of nutritional supplements of selenium for the prevention of two types of skin cancer.

Analysis of Variance↗

Experimental evaluation of perfluorophenanthrene as a high specific gravity vitreous substitute: a preliminary report.

Perfluorophenanthrene, a liquid fluorocarbon with a specific gravity approximately twice that of water, potentially offers certain advantages as a vitreous substitute in vitreoretinal surgery. To determine its efficacy and safety we first purified it by chemical methods used in the preparation of experimental blood substitutes to a level at which it was not at all or only minimally toxic to culture-grown retinoblastoma cells. Nineteen of 22 vitrectomized eyes of white New Zealand rabbits injected with this purified perfluorophenanthrene showed satisfactory clinical tolerance. Light and electron microscopy showed minimal or no toxic effects in the 19 eyes, although uptake of perfluorophenanthrene by some preretinal cells was observed 28 days after implantation. Postoperative light-adapted electroretinography recordings of eight of the injected eyes showed no significant change. Perfluorophenanthrene injected into the anterior chamber of the rabbit eyes had toxic effects on the cornea. If further experimentations confirm our findings, perfluorophenanthrene may be a suitable transparent high-density liquid for temporary use in surgery to repair retinal detachments.

Animals↗

Long-term implantation of voltammetric oxidase/peroxide glucose sensors in the rat peritoneum.

Methods for designing, fabricating, testing in vitro and in vivo, and improving chronically implantable oxidase/peroxide-type polarographic glucose sensors are described. Voltammetric means to evaluate oxygen supply to the sensor and to measure the nearby microcirculation with hydrogen washout techniques using the implanted glucose sensor are outlined. Because some peritoneally implanted sensors have, perhaps surprisingly, remained functional for months, such devices may prove with further development to be useful as the sensing components in artificial pancreatic beta cells for the control of diabetes.

Animals↗

Polarographic cerebral oxygen availability, fluorocarbon blood levels and efficacy of oxygen transport by emulsions.

In order to relate blood perfluorocarbon (PFC) level to brain tissue oxygen availability (aO2) and respiratory oxygen (FIO2), twelve conscious rabbits with chronically implanted platinum cathodes were infused with six types of emulsions in 14 infusions and their response to oxygen and carbogen breathing recorded. Blood was removed for sampling and to avoid a volume overload. Blood lactate was measured as an indicator of adequacy of perfusion. Glucose, osmotic pressure, packed cell volume, PFC by combustion and volatilization were also measured in blood samples. Methyl prednisolone was administered to 5 rabbits. Blood PFC levels measured by the commonly used centrifugation method (Fluorocrit) were subject to considerable variation, depending mainly upon centrifugation time. Fluorocrit values after Oxypherol infusion decreased from an average of 43% for 5 minutes to 15% for 30 minutes centrifugation. Fluorocrit tended to slightly increase with time of centrifugation when phospholipid was used as the emulsifier, early in PFC infusion and on the next day. Blood fluorocarbon was always lower, about half that of 30 minutes of centrifugation, when determined by combustion or by volatilization, than by centrifugation. The increase in brain a O# response to oxygen and carbogen was observed at a lower PFC blood level than expected and in some animals appeared in either the right or left hemisphere, but not in both, suggesting that oxygen transport, at least near the electrode, was by other than oxygen solubility in blood PFC. Blood lactate proved to be an excellent monitor of whole body perfusion. Animals with a blood lactate above 5 mM/L at 1 hour post infusion died the following day. The fluorocrit after 5, 10, 20, and 30 minutes of centrifugation, which we have named the "fluoro-gram," can have a sharp downward, a slight upward curve, or stay level, depending upon the type of emulsifier, the amount of PFC circulating and the time it has circulated. The fluorocarbon-induced increases in aO2 persist through the third day. This enhanced cerebrocortical aO2 current can be very roughly calculated as: aO2 current equals the air aO2 current plus (the 30 minute fluorocrit times K) where K for oxygen is 0.05 and for carbogen is 0.07. Some enhancement of the aO2 current in oxygen lingers to the fifth day after the blood PFC level is vanishingly small. Methyl prednisolone has a transient effect in suppressing the PFC enhanced oxygen and carbogen aO2 responses and no effect on the Oxypherol fluorogram.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The epidemiology of selenium and cancer.

Evidence supporting the hypothesis that decreased Se status is associated with an increased risk of cancer is increasing. This paper reviews the epidemiological studies of the Se and cancer hypothesis and discusses their strengths, limitations, problems of interpretation, and methodological issues.

Basal Cell Carcinoma↗

Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.

Emulsions of fluorocarbons are finding considerable use in physiology for intravascular oxygen transport. Their wide clinical application as blood substitutes, anti-shock, and anti-ischemic agents seems imminent. Whole body NMR imaging is rapidly gaining clinical application and may one day almost completely supplant X-ray imaging. All of the 19F compounds used in biocompatible fluorocarbon emulsions give 19F signals identical to those in the corresponding neat liquid. In concentrations of 10% w/v they are readily imaged. The paramagnetic oxygen molecule reduces T1 in such a way as to make possible whole body imaging of oxygen. T1 typically decreases from 1-4 to 0.3-0.5 seconds and is an inverse linear function of oxygen tension. Spin-lattice relaxation times versus oxygen tensions from 0 to 600 torr have been obtained for F-decalin, F-tributylamine, and F-44E. The usefulness of these 19F effects in clinical NMR imaging depends upon the sensitivity of the method and the tolerable dose. The 19F signal may find use in monitoring 19F compounds as vapors or gases dissolved in plasma or in perfluorocarbons in neat liquid or particle form.

Animals↗