Although serum testosterone levels decrease acutely in critically ill patients, estrogen levels rise. We hypothesized that increased rates of aromatization of androgens to estrogens underlie the increase in serum estrogen levels. Eleven men and three women (age 42-69 yr) were prospectively studied before and again after elective coronary artery bypass graft surgery (CABG). Each patient received priming doses of [(14)C]androgen and [(3)H]estrogen that were immediately followed by peripheral infusions for 210 min. Eight men and three women received androstenedione (A(4))/estrone (E(1)) and three men received testosterone (T)/estradiol (E(2)). Adipose tissue biopsies were obtained in another six men before and after CABG to evaluate levels of P450 aromatase mRNA. Serum T levels decreased postoperatively in all 17 men (P < 0.001), whereas E(1) levels rose (P = 0.004), with a trend toward a rise in E(2) (P = 0.23). Peripheral aromatization rates of androgens to estrogens rose markedly in all 14 patients (P < 0.0001). Estrogen clearance rates rose (P < 0.002). Mean serum A(4) levels increased slightly postoperatively (P = 0.04), although no increase in A(4) production rates (PRs) was observed. T PRs decreased in two of three men, whereas clearance rates increased in all three. Adipose tissue P450 aromatase mRNA content increased postoperatively (P < 0.001). We conclude that the primary cause of increased estrogen levels in acute illness is increased aromatase P450 gene expression, resulting in enhanced aromatization of androgens to estrogens, a previously undescribed endocrine response to acute illness. Both increased T clearance and decreased T production contribute to decreased serum T levels. Animal studies suggest that these opposing changes in circulating estrogen and androgen levels may be important to reduce morbidity and mortality in critical illness.

The gorgonian octocoralLeptogorgia virgulata (Phylum Coelenterata, Class Anthozoa) is rarely overgrown by fouling organisms and is avoided by most predators. Laboratory experiments suggest that secondary metabolites and calcium carbonate spicules interact synergistically to provideL. virgulata with an effective defense against predatory fish. In spite of these defenses,L. virgulata is consumed by the symbiotic, trophically specialized gastropodNeosimnia uniplicata, which closely mimics the appearance of the gorgonian.Neosimnia uniplicata is readily eaten by fish and appears not to acquire an effective antipredator defense from its gorgonian host. Extracts ofLeptogorgia virgulata andNeosimnia uniplicata strongly inhibited the settlement of the barnacleBalanus atnphitrite. Bioassay-directed purification of the more potent antifouling agents fromL. virgulata led to the isolation of two previously described, diterpenoid hydrocarbons, known as pukalide and epoxypukalide. A third inhibitor of barnacle settlement, whose structure is presently unknown, was obtained from bothL. virgulata andN. uniplicata. When assayed for ability to inhibit barnacle settlement, these three compounds possessed EC50 values ranging from 19 to 55 ng/ml. These secondary metabolites may prevent the overgrowth ofL. virgulata by fouling organisms in nature. The allelochemicals ofL. virgulata, N. uniplicata, and other marine organisms may provide nonpolluting alternatives to existing, commercial antifoulants based on derivatives of tri-n-butyltin.

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In this paper we describe a theory of DNA histogram debris generation and compensation that can be applied to paraffin-embedded frozen tissue preparations. The theory predicts the distribution of fragments generated from single and multiple random sectioning of threedimensional ellipsoids representing nuclei. The fragment distribution is assumed to be a major component of the underlying debris in DNA histograms. A comparison of S-phase fractions (SPF) from matched tissue prepared by frozen and formalin-fixed paraffin-embedded DNA methods demonstrates the usefulness of the theory.Key terms: DNA histogram analysis, cell cycle analysis, debris subtraction, debris compensation, S-phase analysis, paraffin processing Although over 100 retrospective clinical flow cytometry studies have examined DNA index and prognosis ( l l ) , less than 15% of these studies attempted to examine S-phase fraction (SPF). This low percentage is presumably due to investigators' lack of confidence in SPF estimates because of paraffin-embedded derived debris contamination in the S-phase region. Haag et al. (9) demonstrated that compensating for debris with either a n algebraic or exponential function yielded SPF estimates that were more comparable with 3H-thymidinelabeling indices. A few studies have compensated for debris with an exponential and have found SPF to be a more important prognostic factor than DNA index (8,2,3).In our own retrospective studies (Bagwell, unpublished results) we have found exponential debris compensation has a strong tendency to overcompensate for debris in the S-phase region in many samples resulting in abnormally low SPF estimates (see Fig. 1). The debris distribution for formalin-fixed paraffin-embedded tissue generally does not decrease as an exponential just prior to the GO-G1 peak. The mismatch in shape between the observed debris distribution and the exponential model component can result in poor computer regression fits and highly variable estimates of SPF.In this paper we present a theory that describes the distribution of debris resulting from random sectioning through nuclei. Although the presented theory is similar to that published by Bins et al. (7), the assumed geometry, calculated probability distributions, and method of compensation is fundamentally different. The shape of the debris curve presented in this paper is calculated from the observed histogram and is subsequently used as a model component in a Marquardt nonlinear least-squares algorithm ( 5 ) . We refer to this type of model component, with its shape derived from the histogram, as a histogram-dependent model component. The initial idea behind this technique was suggested to us by Dr. Dennis Way and Dr. Benjamin Love at the Annual Application Courses held in 1986 and 1987 and more recently a similar compensation algorithm has been implemented by Rabinovitch (13). We describe the theory in detail and test it with matched samples that have been prepared by frozen and paraffin-embedded DNA methods. MATERIALS AND METHODS Sample Selection, ...

The statewide registry showed a postoperative stroke plus death rate of 2.8%, comparable with the NASCET and ACAS findings. Although this study had inherent limitations, the results from one state, including a variety of community practices, achieved results comparable with those of landmark trials.