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Biomedical subjects

L C Clark

Publications and source records attributed to L C Clark.

At least 19 recordsLinked to original sources
PubMed1992

Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy.

BACKGROUND: Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS: Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported in patients with ICM. CONCLUSIONS: These data suggest that increased myocyte length (an intracellular event), instead of myocyte slippage (an extracellular event), is largely responsible for the chamber dilation in ICM. Furthermore, maladaptive remodeling of myocyte shape (e.g., increased myocyte length/width ratio) may contribute to the elevated wall stress (e.g., increased chamber radius/wall thickness) in ICM.

Animals↗
PubMed1992

Arterial blood gases and brain oxygen availability following infusion of intratracheal fluorocarbon neat liquids.

Eight adult New Zealand Swiss rabbits (3-5 kg) having previously implanted chronic bilateral platinum electrodes in the visual cerebral cortex and subcutaneous silver reference electrodes were tranquilized and monitored in multiple 2-3 hour sessions using voltammetric techniques. Six of these were given intratracheal neat liquid fluorocarbons ranging in boiling point from 132 degrees C to 215 degrees C at doses of 2 or 4cc/kg. Each animal received only one fluorocarbon liquid. Two additional rabbits were match-studied as controls. Half of the rabbits have survived more than five months. Both controls and two experimental rabbits were sacrificed after more than seven months due to gastric hairballs. The period of daytime monitoring sessions, when cathodic brain oxygen currents (aO2), arterial blood gases and pH were obtained, was between 34 and 263 days. In some animals the arterial pCO2 was increased during the first week but the pO2 and pH remained nearly normal in all eight animals throughout. The two best fluorocarbons for liquid breathing on the basis of this limited but intensive work are F-methyldecalin and F-5,6H-dec-5-ene (F44E).

Animals↗
PubMed1992

Response of the rabbit lung as a criterion of safety for fluorocarbon breathing and blood substitutes.

From the first liquid breathing experiments until now, the lung, not surprisingly, has played a central role in the evolution of fluorocarbon blood substitutes. The first breathable fluorocarbon, a mixture of F-alkylfurans(FC75), bp 102 degrees C, while a poor solvent for the lung's lining and a good solvent for oxygen and carbon dioxide, proved to cause a characteristic gas/vapor microbubble embolism following intravenous administration as an emulsion. Higher boiling fluorocarbons, e.g. F-tributylamine (FC47), bp 174 degrees C, do not produce such gas-vapor emboli. However, intermediate boiling compounds such as F-decalin (PP5), bp 141 degrees C, produce lungs which, although they certainly appear not to contain microbubble emboli, do not collapse when the thorax is opened. Such hyperinflated non-collapsible lungs (HNCL) occur in the rabbit after the intravenous infusion of F-decalin emulsions as well as after the intratracheal infusion of F-decalin neat liquid. F-decalin induced HNCL retain their appearance and low specific gravity for many weeks, gradually returning toward normal after many months. F-methyl decalin, bp 165 degrees C, does not cause HNCL after intravascular or intratracheal administration. Fluorocarbons having boiling points between 140 degrees C and 165 degrees C are being tested in order to find a perfluorinate with the highest transpiration rate, and hence vapor pressure, compatible with an acceptable body dwell time. We have given fluorocarbons intratracheally to 75, intravenously to 221 and both intratracheally and intravenously to 8 rabbits. Free radical trapping agents, antineutrophil, antiinflammatory and other drugs have been administered without appreciable decrease of HNCL. Fluorocarbon critical solution temperature, lipid solubility, emulsifiability, and other physicochemical properties may mediate the pulmonary effect. One method of preventing and treating low dose F-decalin-induced HNCL in rabbits is described.

Animals↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗