Incidence of advanced intravenous access in 2 urban EDs.

BACKGROUND: In an emergency department (ED), intravenous (IV) access is frequently accomplished by inspection and palpation of peripheral veins. Failure of these methods indicates severe IV access difficulty and necessitates advanced techniques. Here, we estimate the incidence of advanced IV access in 2 urban EDs with varying resident coverage. METHODS: In this multiple-cohort study, we enrolled data from 2 neighboring urban EDs-a tertiary care ED and a community hospital affiliate. The 2 have similar volumes but the tertiary care ED has more resident coverage (112 vs 20 hours/d). In a prospective data collection (April 2012-2013), we enrolled consecutive patients during hours of scheduled shifts for research assistants. In a retrospective data collection (March 2011-2012), we reviewed charts of a random sample of patients from each ED for similar outcomes. We calculated the incidence of advanced IV access by dividing the number requiring advanced techniques by the number requiring IV access. RESULTS: We determined IV outcomes for 790 patients in the prospective cohort and 669 patients in the retrospective cohort. Between groups, there was no difference in the incidence of advanced IV access in the prospective collection (P = .08) or in the retrospective collection (P = .7). Pooling data from both cohorts and both hospitals, the overall incidence was 3.2 [95% confidence interval, 1.9-5.2] per 100 attempts. CONCLUSION: Advanced IV access is needed in 3.2% of IV attempts in 2 urban EDs with varying levels of resident coverage. We found similar incidence in both EDs.

Tumor progression in serial passages of the Dunning R3327-G rat prostatic adenocarcinoma: growth rate response to endocrine manipulation.

Serial passages of the poorly differentiated, androgen-sensitive R3327-G prostatic adenocarcinoma were used to study the progressive changes that occur in tumor growth rate and androgen sensitivity. Different in vivo transplant generations (21st to 28th) were compared. The tumor doubling and animal survival times resulting from the implantation of the 21st to 22nd generation (21-22G) tumor cells in intact male rats were significantly greater than those resulting from the implantation of 23-28G tumor cells. The most dramatic difference between early (21-23G) and late (26-28G) tumor generations, however, was in androgen sensitivity. The 26-28G tumors displayed androgen sensitivity only when implanted into animals castrated 2 to 7 days previously. Tumors grown in the pretreated castrates grew at a significantly slower rate than those in intact rats and the pretreated castrates had longer survival times than the intact rats. When 26-28G tumors were allowed to grow in intact rats to approximately 1 cu cm and then the rats were castrated, no significant difference in the growth rate between these tumors and tumors grown in intact rats was observed. In contrast, the androgen sensitivity of 21-23G tumors could be demonstrated, regardless of whether treatment was started before or after implantation. The fact that androgen sensitivity was still evident under certain conditions in late-generation R3327-G tumors demonstrates that the basic mechanism involving androgen response was still present, although functioning at a much reduced level.

Effects of the gonadotropin-releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) on R3327-G rat prostatic tumor growth.

The synthetic gonadotropin releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) was tested for its ability to inhibit androgen-sensitive R3327-G rat prostatic tumor growth in Copenhagen X Fischer F1 male rats. The chronic administration of leuprolide at 50 micrograms per kg. body weight or 1000 micrograms per kg. body weight significantly reduced serum testosterone levels and testis weights. Only chronic leuprolide administration at high concentration (1000 micrograms per kg.) compared with orchiectomy in reducing the rate of tumor growth, prolonging survival, and affecting changes in DNA content per cell as quantitated by flow cytometry. The DNA content changes and cell kinetic responses of R3327-G tumors to these treatments were related to the extent to which serum testosterone levels were reduced. The data suggest that for some prostatic cancers gonadotropin releasing hormone agonist administration must reduce serum testosterone levels to those achieved by orchiectomy for maximal growth rate inhibition.

In vivo selection of androgen-insensitive cells in R3327-G rat prostate tumors: diethylstilbestrol diphosphate treatment versus orchiectomy.

Tumors grown in diethylstilbestrol diphosphate (DES)-treated rats grew significantly more slowly than tumors grown in orchiectomized animals, and tumors grown in orchiectomized animals grew significantly more slowly than tumors grown in controls (intact male rats). When these tumors (phase I) were dispersed and reimplanted into DES-treated, orchiectomized, or control rats in all possible combinations (phase II), a partial selection of androgen-insensitive cells was observed in tumors grown in DES-treated animals. Tumors grown in DES-treated phase I animals responded significantly less to DES treatment or orchiectomy in phase II. In contrast, tumors from phase I orchiectomized animals showed the same responses to orchiectomy in phase II. Since the administration of exogenous testosterone propionate prevented the growth rate inhibitory effects of both DES treatment and orchiectomy, the added effect of DES seemed to be antiandrogenic.

Effects of Thorotrast in humans.

Thorotrast, a patented radiological contrast medium that was widely used from 1930-1950, is a thorium dioxide colloid that has been neutralized and stabilized by protective colloids, which are decomposition products of starch, and which are now generally known as dextrans. The deposition of Thorotrast depends on its radiological use, its method of preparation, and the age of the preparation; however, the major site is the reticulo-endothelial system, where it is retained for long times. Some of its decay products, principally 228Ra and 224Ra, escape from the colloidal particles and deposit in the skeleton. The biological end-points that have been observed in the several human populations that are known to have received Thorotrast are Thorotrastomas, malignant hepatic neoplasms, and other neoplasms of the reticulo-endothelial system (RES), skeletal sarcomas, and leukemias in excess of the number expected. The question to be reviewed in this paper is whether irradiation, or chemical and mechanical effects on the reticulo-endothelial system, or a combination thereof, is the causative factor in the occurrence of these RES neoplasms.

Hormone sensitivity of the R3327-G rat prostate adenocarcinoma: growth rate, DNA content, and hormone receptors.

The growth of the R3327-G rat prostatic adenocarcinoma was significantly reduced when implanted in orchiectomized male rats (ORCH tumors). Tumors grown in intact animals (control tumors) had a doubling time of 7.4 days as compared to 9.2 days in ORCH tumors. A computer-based analysis of flow cytometric DNA histograms also detected significant differences between control and ORCH tumors. ORCH tumors were found to have 25% fewer cells with hyperdiploid DNA than control tumors (p less than 0.01). This androgen sensitivity in growth rate and the proportion of hyperdiploid cells were further reflected in the binding of [3H]methyltrienolone ([3H]-R1881) to cytoplasmic (cytosol) and nuclear tumor extracts. ORCH tumor cytosols had a [3H]R1881 binding capacity which was 70% lower than controls (6071 fmol/g tumor tissue). Nuclear [3H]R1881 binding in ORCH tumors was undetectable in seven of eight samples while in control tumors, binding was detectable in five of six preparations. Sucrose density gradient analysis showed that cytosolic [3H]R1881 receptors sedimented at 8.1 S in low salt and 4.6 to 3.3S in high salt. Nuclear [3H]R1881 receptors in high salt sedimented at 4.1 to 3.3S. Competition experiments using [3H]R1881 showed that [3H]-R1881 receptors were primarily androgenic, although some displacement by estradiol did occur. In contrast, [3H]estradiol binding was found to be highly specific. The binding capacity of [3H]estradiol in ORCH tumor cytosols was 30% higher than controls (962 fmol/g tumor issue), while binding to ORCH and control nuclear extracts was similar. These data suggest that the inhibition of androgen-sensitive R3327-G tumor cells was related to the concentration of androgen receptors and that this in turn was expressed as a reduction in the proportion of hyperdiploid cells.

Flow cytometric analysis of the response of the R3327-G rat prostatic adenocarcinoma to endocrine manipulation.

The technique of flow cytometric DNA histogram analysis (FCM) shows there to be two distinct cell populations (diploid vs aneuploid) in the poorly differentiated R3327-G rat prostatic adenocarcinoma. The following study compares tumor weight measurements with several FCM computer-based methods designed to determine rapidly the proliferative status of tumors. Hypophysectomy, bilateral adrenalectomy, orchiectomy, sham operations, or diethylstilbestrol treatments were initiated when the tumors were palpable (day 21) and continued until the tumors were excised (day 52). Hypophysectomy, orchiectomy, adrenalectomy, and diethylstilbestrol treatments all resulted in significant inhibition by tumor weight. Quantitation of the percentage of mid-S phase aneuploid cells by summation gave the best correlation with tumor weight. Tumors grown in hypophysectomized, orchiectomized, adrenalectomized, or diethylstilbestrol-treated animals showed a significant reduction in the proportion of mid-S phase cells as compared with controls. The calculation of the percentage of all aneuploid cells was significantly reduced in hypophysectomy, orchiectomy, and diethylstilbestrol-treated animals. However, tumors grown in adrenalectomized animals were not significantly different from controls by this method. Adrenalectomy was found to be the least effective form of therapy, and this was reflected in all of the parameters measured. These data show that FCM analysis may be useful in the quantitation of prostatic carcinoma response to therapy.

The dynamics of life: aging.

Biologic aging arises from various causes, including deterioration of cells by mutations, destruction of the cells in organs through infections, aging by failure to eliminate harmful waste products, poisoning from external sources, and by radiation damage. All of these processes lead to equations of the kind observed experimentally for the aging process, so that a proper assessment of the various factors contributing to aging is especially complicated. Many nonbiological processes in which the products of reaction speed up the aging reaction lead to the familiar equation for the rate of aging. Corrosion of metals is exhibited as a typical example of this; many other examples could be given. The general equation for depth of anesthesia brought about by lipid-soluble materials and how this effect can be mimicked by accumulation of waste products is shown to simulate the typical aging curve; it is well known that such waste products are a frequent cause of death.

The dynamics of life. V. Applying the steady-state theory of mutations to human cancer.

In papers I, II, and III of this series the steady-state theory of mutations was developed and applied to the extensive data on the effect of radiation on beagles acquired here during the past twenty years. In this paper the theory is used to interpret H. B. Dorn's data on the incidence of 21 kinds of cancer in both male and female Americans. The theory shows the nature of the heterogeneity in the population of various disorders. The agreement found confirms the steady-state theory of mutations in an interesting way.

The dynamics of life, 3. Mechanisms of nonsurvival and the relation of dose size.

From the steady-state theory of mutation rates we have the probability, q, of the occurrence of a critical change at some site in a cell that leads to genetic alternation, and the probability, p = 1 - q, that the site either is not changed or that it has been repaired. In this paper the formal theory is extended to include survival of biological systems. Single and multiple mechanisms of nonsurvival, and multiple factors acting on a single mechanism, are considered. The number of sites that must be altered to lead to nonsurvival is examined and found to be greater than one. The effect of independent action on separate sets of sites, and the relationship between dose size and survival time are given.

The dynamics of life. II. The steady-state theory of mutation rates.

The statistical effect of internal irradiation on the survival of beagles is similar to that of aging, with the exception that death occurs earlier. Since biological processes are close to equilibrium most of the time, the above observation suggests that death ensues when the rate of insult has exceeded the rate of recovery to a sufficient extent that the reserves are depleted and the steady state can no longer be maintained. The steady-state theory of mutation rates is derived from first principles, and, through absolute rate theory, is completely general and is not limited to a specific kind of cellular alteration. However, the nature of the cellular alterations that lead to nonsurvival are considered. The young growing system is also considered in the context of this theory.