Androgen- and estrogen-receptor content in spontaneous and experimentally induced canine prostatic hyperplasia.

To gain insight into the mechanism by which steroidal hormones influence the development of canine prostatic hyperplasia, nuclear and cytosolic androgen- and estrogen-receptor content, as measured under exchange conditions by the binding of [(3)H]R1881 (methyltrienolone) and [(3)H]estradiol, respectively, were quantitated in the prostates of purebred beagles of known age. In young dogs with spontaneously arising and experimentally induced (androstanediol plus estradiol treatment) prostatic hyperplasia, nuclear, but not cytosolic, prostatic androgen-receptor content was significantly greater than that determined in the normal prostates of age-matched dogs (3,452+/-222 and 4,035+/-274 fmol/mg DNA vs. 2,096+/-364 fmol/mg DNA, respectively). No differences were observed between the androgen-receptor content of the normal prostates of young dogs and the hyperplastic prostates of old dogs. The cytosolic and nuclear estrogen-receptor content of spontaneously arising prostatic hyperplasia in both young and old animals was similar to that found in normal prostates. The administration of estradiol plus androstanediol to castrate dogs significantly increased the prostatic nuclear androgen-receptor content over that found in dogs treated only with androstanediol. This estradiol-associated increase in nuclear androgen-receptor content was accompanied by the development of benign prostatic hyperplasia. Estradiol treatment of castrate dogs resulted in an increase in prostatic nuclear estrogen-receptor content, in the appearance of a putative prostatic cytosolic progesterone receptor, and in an alteration of the epithelium of the prostate to one characterized by squamous metaplasia. Treatment of castrate dogs with both estradiol and androstanediol resulted in a reduction in prostatic nuclear estrogen-receptor content, disappearance of the progesterone receptor, and loss of squamous metaplasia. An increase in nuclear androgen-receptor content, thus, appears to be an important event in the development of both spontaneously arising and experimentally induced canine prostatic hyperplasia. The mechanism of androgen-estrogen synergism in the experimental induction of canine benign prostatic hyperplasia may be explained by estradiol-mediated increases in nuclear androgen-receptor content. Because androstanediol blocked certain estradiol-mediated events within the prostate, a negative feedback mechanism may exist in which the response of the canine prostate to estrogens is modulated by rising levels of androgen.

Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues.

The potent synthetic androgen methytrienolone (R 1881), which does not bind to serum proteins, was utilized to characterize binding to receptors in human androgen responsive tissues. Cytosol extracts prepared from hypertrophic prostates (BPH) were utilized as the source of receptor for the initial studies. High affinity binding was detected in the cytosol of 29 of 30 samples of BPH (average number of binding sites, 45.8+/-4.7 fmol/mg of protein; dissociation constant, 0.9+/-0.2 nM). This binding had the characteristics of a receptor: heat lability, precipitability by 0-33% ammonium sulfate and by protamine sulfate, and 8S sedimentation coefficient. High affinity binding was also detected in cytosol prepared from seminal vesicle, epididymis, and genital skin but not in non-genital skin or muscle. However, similar binding was demonstrated in the cytosol of human uterus. The steroid specificities of binding to the cytosol of male tissues of accessory reproduction and of uterus were similar in that progestational agents were more effective competitors than natural androgens. Binding specificities in cytosol prepared from genital skin were distinctly different and were similar to those of ventral prostate from the castrated rat in that dihydrotestosterone was much more potent than progestins in competition. Thus binding of R 1881 to the cytosol of prostate, epididymis, and seminal vesicle has some characteristics of binding to a progesterone receptor. When the nuclear extract from BPH was analyzed, high affinity binding was demonstrated that conformed to the specificities of binding to an androgen receptor. Here dihydrotestosterone was a more potent competitor than progestational agents. Similar patterns of binding were detected in the crude nuclear extracts from seminal vesicle, epididymis, and genital skin but not in uterus, muscle, or non-genital skin. We conclude that the androgen receptor is not demonstrable in the cytosol of prostate, epididymis, or seminal vesicle of non-castrated men but can be measured in the cytosol of genital skin and the nuclear extracts of androgen responsive tissues. Because steroid hormones exert their major influence within the nucleus of target tissues, the measurement of nuclear receptor may provide valuable insight into the regulation of growth of target tissues.

Estrogen receptors in the human prostate, seminal vesicle, epididymis, testis, and genital skin: a marker for estrogen-responsive tissues?

In an effort to identify those human male sex accessory tissues that may be under the physiological influence of estrogen, cytosolic and nuclear estrogen receptors were measured with two ligand systems that used either [3H]R2858 [moxesterol(11 beta-methoxy-17-ethynyl-1,3,5,(10)-estratriene-3,17 beta-diol)] or [3H]estradiol plus 1 microM dihydrotestosterone with diethylstilbestrol to correct for nonspecific binding. In seminal vesicles, high affinity binding was identified in cytosol (6 of 7 determinations) and nuclear extract (4 of 7 determinations); in the epididymis, high affinity binding was also present in the cytosol (10 of 12 determinations) and nuclear extract (10 of 11 determinations). In contrast, no high affinity binding was demonstrated in cytosol from the testis (0 of 5 determinations) or genital skin (0 of 7 determinations), and only low levels of nuclear receptor (80 fmol/g tissue) were present in the testis (3 of 5 determinations) and genital skin (1 of 7 determinations). In nonhyperplastic prostatic tissue, high affinity binding was present [in the cytosol of periurethral zone tissue (3 of 7 determinations) and nuclear extract (1 of 7 determinations), in cytosol of peripheral zone tissue (7 of 8 determinations) and nuclear extract (4 of 7 determinations), and in prostatic carcinoma cytosol (5 of 12 determinations) and nuclear extract (10 of 13 determinations)]. In contrast, no high affinity binding was present in either cytosol or nuclear extract from benign hyperplastic prostatic tissue. The finding of estrogen receptors in the human epididymis, seminal vesicle, and prostatic carcinoma suggests that estrogen, in addition to androgen, may act in the physiological regulation of these organs. However, the direct role of estrogen in the induction and maintenance of benign prostatic hyperplasia remains to be defined.

A microassay for the measurement of androgen receptors in human prostatic tissue.

A microassay utilizing R 1881 (methyltrienolone) has been developed for the measurement of androgen receptor sites in the cytosol and nuclear extract of human prostatic tissue. Binding of R 1881 to the progesterone binding molecule in cytosol was eliminated by the addition of triamcinolone acetonide. Utilizing a six tube, single point assay, the number of binding sites estimated in nuclear extract averaged 95% of the number measured by a full 7 point Scatchard analysis; the number estimated by the microassay in cytosol averaged 91%. When the single point assay was applied to needle biopsy specimens (200 mg of tissue), the estimated number of binding sites in nuclei averageed 83% of the number measured in bulk tissue (2 grams) utilizing a 7 point Scatchard analysis; the number in cytosol estimated by the microassay on needle biopsy specimens averaged 73%. It is hoped that this technique may be useful in correlating receptor content with hormonal responsiveness in men with metastatic carcinoma of the prostate.

Randomized clinical trial of a quality improvement intervention in nursing homes.

PURPOSE: The purpose of the study was to determine if simply providing nursing facilities with comparative quality performance information and education about quality improvement would improve clinical practices and subsequently improve resident outcomes, or if a stronger intervention, expert clinical consultation with nursing facility staff, is needed. DESIGN AND METHODS: Nursing facilities (n = 113) were randomly assigned to one of three groups: workshop and feedback reports only, workshop and feedback reports with clinical consultation, and control. Minimum Data Set (MDS) Quality Indicator (QI) feedback reports were prepared and sent quarterly to each facility in intervention groups for a year. Clinical consultation by a gerontological clinical nurse specialist (GCNS) was offered to those in the second group. RESULTS: With the exception of MDS QI 27 (little or no activity), no significant differences in resident assessment measures were detected between the groups of facilities. However, outcomes of residents in nursing homes that actually took advantage of the clinical consultation of the GCNS demonstrated trends in improvements in QIs measuring falls, behavioral symptoms, little or no activity, and pressure ulcers (overall and for low-risk residents). IMPLICATIONS: Simply providing comparative performance feedback is not enough to improve resident outcomes. It appears that only those nursing homes that sought the additional intensive support of the GCNS were able to effect enough change in clinical practice to improve resident outcomes significantly.

Increasing role of economic analysis in the health care industry.

As the health care industry continues to absorb an ever-larger portion of society's resources, increasing pressure is being placed on the industry to justify its decisions about the outcomes of the services it renders relative to their costs. Emphasis is being shifted from accessibility to and availability of health care to the cost-effective delivery of those services. This focus on cost effectiveness is creating intense pressure on the various segments of the industry to justify their existence as cost-effective providers of services. To demonstrate cost effectiveness, the various segments are searching for tools to assist them. In this article, an outline of a mechanism for evaluating the cost effectiveness of providing physical therapy services is presented.

Availability and accessibility of rural health care.

The 1980s saw a retrenchment of the ideology that government intervention could solve the problems of inadequate access to health services in rural areas. Increased emphasis was placed on an ideology that promoted deregulation and competitive market solutions. During the 1980s, the gap in the availability of physicians in metropolitan versus nonmetropolitan areas widened. Also during that time period, the gap between metropolitan and nonmetropolitan populations' utilization of physician services widened. In addition, many indicators of the health status of nonmetropolitan residents versus metropolitan residents worsened during the 1980s. As we enter the 1990s, concern about equitable access to needed health care services and for the vulnerability and fragility of rural health systems has resurfaced. A number of national policies and a research agenda to improve accessibility and availability of health services in rural areas are being considered.

Rural populations and rural physicians: estimates of critical mass ratios, by specialty.

As physicians and other providers of health care services see their traditional markets erode, an increasingly important element of any provider location decision is the determination of a population base or "critical mass" that can professionally and financially support a given set of health care services. While the size of a local population is not the sole determinant of success, ultimately an adequate population base to support a given spectrum of services must be defined, and providers increasingly need tools for evaluating opportunities in the new economic market. This is especially true in rural areas. An earlier supply and demand model for estimating the critical mass of population needed to support a physician in any one of 25 specialties and subspecialties in urban and suburban areas is adapted to the rural market. The assumptions inherent in the earlier model are examined and the issue of "critical mass" is examined from a rural health care perspective in this paper.

Effects of second office and hospital consulting practices of physicians on rural communities.

This research examined the prevalence of second offices and hospital consulting practices of physicians in Missouri, the characteristics of physicians participating in such practices, the change in availability of services through these practices, the characteristics of counties and hospitals involved, and the practice organization of participating physicians. The assessment of the factors was conducted within the conceptual framework of community and physician characteristics, practice form and organization, and health system resources. In 1993, 64 of the 93 nonmetropolitan counties in Missouri gained, on average, 1.3 full-time equivalent physicians through second office and hospital consulting practices. Eighteen nonmetropolitan counties lost, on average, 0.4 full-time equivalent physicians through these practices; 11 nonmetropolitan counties were not affected. The majority of physicians engaged in these two types of practices are nonprimary care specialists. Consequently, in addition to the net contribution to total physician service availability, many nonmetropolitan counties gained access locally to a wider variety of specialty services. This change in availability of physician services, not generally incorporated in decisions, needs to be considered when policy efforts are undertaken to change the spatial and specialty distribution of physicians.

Necessary conditions for supporting a general surgeon in rural areas.

Loss of a general surgeon in a rural community cna alter the referral patterns, the image and utilization of the local hospital, and even the market share of local primary care physicians. Prior research has not defined the necessary and/or sufficient conditions for a rural county to be able to support a local general surgeon. Based upon empirical analysis of 96 rural Missouri counties and the limited literature available on rural surgeons and physician referral rates, a first approximation of those conditions are offered. We conclude that a rural county with a hospital, a population base of more than 15,000 people, and at least 11 potential referring physicians has sufficient conditions to enable it to support a local general surgeon. Among those rural Missouri counties not meeting the above conditions but having a general surgeon in 1984, we estimate that 8 to 10 potential referring physicians appear to be the minimum necessary condition for supporting a rural general surgeon through patient referral. From those conclusions, we argue that any rural hospital currently without a surgeon should re-examine its situation. To prepare for a competitive future, such a hospital should take every opportunity to expand the referral base necessary to support a full-time local surgeon rather than place long-term reliance upon itinerant general surgeons.

Using telemedicine to avoid transfer of rural emergency department patients.

Access to emergency treatment in rural areas can often mean the difference between life and death. Telemedicine technologies have the potential of providing earlier diagnosis and intervention, of saving lives and of avoiding unnecessary transfers from rural hospital emergency departments to urban hospitals. This study examined the hypothetical impact of telemedicine services on patients served by the emergency departments of two rural Missouri hospitals and the potential financial impact on the affected hospitals. Of the 246 patients transferred to the hub hospital from the two facilities during 1996, 161 medical records (65.4 percent) were analyzed. Using a conservative approach, only 12 of these cases were identified as potentially avoidable transfers with the use of telemedicine. Of these 12, 5 were admitted to the hub hospital after transfer. In addition to this conservative estimate of avoidable transfers based on current availability of resources in the rural hospitals, two more aggressive scenarios were developed, based on an assumption of increased service availability in the rural hospitals. Economic multipliers were used to estimate the financial impacts on communities in each scenario. This evaluation study demonstrates the potential value of telemedicine use in rural emergency departments to patients, rural hospitals and rural communities.

Profitable capitation requires accurate costing.

In the name of costing accuracy, nurses are asked to track inventory use on per treatment basis when more significant costs, such as general overhead and nursing salaries, are usually allocated to patients or treatments on an average cost basis. Accurate treatment costing and financial viability require analysis of all resources actually consumed in treatment delivery, including nursing services and inventory. More precise costing information enables more profitable decisions as is demonstrated by comparing the ratio-of-cost-to-treatment method (aggregate costing) with alternative activity-based costing methods (ABC). Nurses must participate in this costing process to assure that capitation bids are based upon accurate costs rather than simple averages.

Assessing contributors to cost of care in nursing homes.

In 1994 12.7% of the population was 65 and over, while 10.6% were 85 and over. Expenditures for nursing homes reached $72.3 billion in 1994 (much of which is tax-supported) accounting for 8.7% of all personal health money spent. Data from the 1993 Missouri Medicaid cost reports for 403 nursing homes were reviewed to determine differences in costs per resident day (PRD) and discover which factors most influenced these differences. Mid-sized facilities with 60-120 beds reported the lowest resident-related PRD costs. PRD expenses for aides and orderlies were higher in tax-exempt facilities, which was thought to be related to their "more altruistic" mission. Investor-owned facilities showed significantly greater administrative costs PRD, which may relate to higher administrative salaries and fancier offices. The authors suggest further study that would incorporate location, occupancy rate, quality of care, case mix, and payer mix data.

An evaluation of satisfaction with telemedicine among health-care professionals.

A survey was conducted among non-doctor health-care professionals in six rural counties in Missouri. The purpose of the survey was to establish baseline data to evaluate the effect of changes in the health-care sector, especially technology changes, on the job satisfaction, career satisfaction, relationships and communication activities of health professionals. The survey included three rural counties in which integrated telecommunication and interactive video telemedicine services were being installed, but before significant activities had begun, and three comparator counties without substantial integrated telecommunications infrastructure and telemedicine services. During a one-month study period, 1108 questionnaires were distributed. The total response rate was 50.1% (n = 555). Of the respondents, 30.3% indicated that technology in health-care was having a large effect on their work, although only 18.2% indicated that telemedicine and telecommunications were having a large effect. No systematic differences were found among the health professionals in the two communities at the time telemedicine equipment was being installed.

A method for identifying comparison counties: application to a rural telemedicine evaluation project.

The evaluation of telemedicine activity in rural communities is complicated by the fact that most telemedicine sites are chosen because of their existing telecommunications infrastructure and institutional relationships, not by a random selection process. In addition, it is difficult to draw conclusions about the effects of telemedicine without a careful analysis of parallel changes in communities which do not have access to telemedicine services. We have developed a method of identifying comparable counties based on an aggregate measure of health status. A set of 66 variables was collected in a previous project to develop a model to evaluate the relative health status of the population in Missouri. A stepwise regression was used to identify a subset of 15 variables that had the highest predictive value for the health status of a county. Distance measures were then used to identify six counties which were most similar to three telemedicine counties. The method can be used with any study set chosen non-randomly, to identify similar objects that can be used for comparative purposes.

A compilation of state activities in legislatively mandated reporting of health services data.

The health care crisis and efforts for reform have taken a variety of forms. Apparently a majority of states have decided that the federal government will develop solutions to this problem slowly, if at all, and have undertaken a variety of activities on their own to address the problem. One state response has been to mandate the collection of data related to health services in an effort to assist purchasers of health care to make more prudent buying decisions. This article contains the results of a survey conducted among the states that have legislatively mandated the collection of health-related data and presents a compilation and discussion of their activities.

CAH to CAH: EHR implementation advice to critical access hospitals from peer experts and other key informants.

UNLABELLED: The US government allocated $30 billion to implement electronic health records (EHRs) in hospitals and provider practices through policy addressing Meaningful Use (MU). Most small, rural hospitals, particularly those designated as Critical Access Hospitals (CAHs), comprising nearly a quarter of US hospitals, had not implemented EHRs before. Little is known about implementation in this setting. Socio-technical factors differ between larger hospitals and CAHs, which continue to lag behind other hospitals in EHR adoption. OBJECTIVE: The main objective is to provide EHR implementation advice for CAHs from a spectrum of experts with an emphasis on recommendations from their peers at CAHs that have undertaken the process. The secondary objective is to begin to identify implementation process differences at CAHs v. larger hospitals. METHODS: We interviewed 41 experts, including 16 CAH staff members from EHR teams at 10 CAHs that recently implemented EHRs. We qualitatively analyzed the interviews to ascertain themes and implementation recommendations. RESULTS: Nineteen themes emerged. Under each theme, comments by experts provide in-depth advice on all implementation stages including ongoing optimization and use. We present comments for three top themes as ranked by number of CAH peer experts commenting - EHR System Selection, EHR Team, and Preparatory Work - and for two others, Outside Partners/Resources and Clinical Decision Support (CDS)/Knowledge Management (KM). Comments for remaining themes are included in tables. DISCUSSION: CAH experts rank the themes differently from all experts, a likely indication of the differences between hospitals. Comments for each theme indicate the specific difficulties CAHs encountered. CAH staffs have little or no EHR experience before implementation. A factor across themes is insufficient system and process knowledge, compounded by compressed implementation schedules. Increased, proactive self-education, via available outside partners and information resources, will mitigate difficulties and aid CAHs in meeting increased CDS requirements in MU Stages 2 and 3.