U.S. Federal Government attempts to promote primary care training.

The federal government of the United States is concerned that only 30-33% of physicians are in primary care practice and not more than approximately 15-20% of recent medical graduates choose primary care. Moreover, the distribution of interns and residents in primary care in recent years is 40% and after "branching" it is realistically only 25%. The federal government's goal through legislative intervention is to increase the pool of U.S. medical graduates to enter primary care from the current level to at least 50% by the turn of the century. To attain this goal, the government is depending on health care reform legislation and making changes in federal legislation that reimburses graduate medical education through direct and indirect Medicare payments. The federal government hopes to produce incentives to increase the pool of primary care physicians and to place disincentives on subspecialty training by altering direct and indirect Medicare payments in favor of primary care training programs; by limiting residency and fellowship slots; and by removing limits on direct payments at ambulatory care sites for training, including non-hospital settings. There is concern among medical educators that these changes in current legislative interventions will not increase to 50% the numbers of medical graduates choosing primary care careers. Accredited residency and fellowship programs need to assess projected manpower needs immediately to justify their positions for achieving a balanced physician workforce for the twenty-first century.

Impact of President Clinton's Health Security Act on residency programs.

The Clinton Health Security Act calls for a major shift in the emphasis of medical training. While family practice, general pediatrics, general internal medicine, and obstetrics and gynecology stand to benefit, other specialties will see decreases in their programs and their residency slots. In light of the present sparsity of programs in family practice and the prevalent student disinterest in the specialty, only heroic efforts will make possible achievement of the 55/50 ratio of primary care physicians to other specialists outlined by the Clinton plan. Problems inevitable in the transition are described and incentives for change suggested.

AIDS: public response to a telephone information system.

This article reports on Roswell Park Memorial Institute's experience with a taped, telephone information system in the dissemination of informational and educational messages to the public concerning cancer and AIDS. This system, known as CAN-DIAL, has serviced over 400,000 callers since its inception in 1973. A series of tape recorded messages concerning AIDS was introduced in 1984. This study compares and contrasts basic demographic data on approximately 100,000 callers for cancer and AIDS information for the period 1984 to 1988. Results demonstrate CAN-DIAL to be a well-received, responsive, and efficient means of educating the public about cancer and AIDS.

The use of goal attainment scaling to evaluate a cancer research training program for high school and college students.

Goal attainment scaling has been used frequently in the evaluation of mental health services. The purpose of this study was to assess the usefulness of the goal attainment scaling methodology in the evaluation of a cancer research training program. Subjects were 62 high school and college students participating in a summer research program. Prior to the program, all students were asked to predict the specific outcomes they expected to attain in relation to eight independent dimensions of the research training program. At the close of the program students were asked to indicate the outcome they attained for each dimension. Students also ranked the importance of each dimension. The analyses indicated that participants entered the program with accurate expectations of their ultimate achievement and satisfaction with the program. Significant differences were found for expected outcomes on a number of program dimensions for the high school and college students at the preprogram assessment. Significant differences were also found for the high school and college students' importance rankings at both the pre-program and post-program period. Goal attainment scaling proved to be a valuable and flexible technique for the evaluation of a cancer research training program.

The effects of interferon on murine erythropoiesis.

The effects of interferon (IF) on erythropoietin (Ep) action and production were studied in mice. In comparison to control animals, Ep action in exhypoxic, polycythemic mice was significantly decreased (p less than 0.05) following two low dose injections of IF (2.9-3.5 X 10(4) units). In addition, renal Ep production in normal intact mice was also significantly decreased (p less than 0.01) following a single injection of IF (5.4-6.3 X 10(4) units) and hypoxic exposure.

A graduate program designed for medical and other doctoral degree applicants.

The data collected during the evaluation of the natural science program at Roswell Park revealed a high rate of success in preparing students to enter health and science related careers. An average of 50 percent of the entering students each year had been unsuccessful medical school applicants or students preparing to enter Ph.D. programs following an initial research experience. The program assists students in admission to medical and research programs and encourages research participation. Many graduate programs will not accept or find difficulty dealing with students who have career goals in medicine and are not necessarily in research. This is understandable, especially in Ph.D. granting programs with substantial investments of faculty time and funding. The philosophy of the program reported here is to assist the students to enter the career of their choice; however, at the same time, the faculty members insist on a high level of scholarship in course work and research during the program. With this philosophy, the program continues to be successful in attracting students of high quality.

Protection of normal tissues with 2-aminoethylisothiouronium during local pelvic radiation in monkeys.

Intestinal and bladder injury are the main limiting factors to radiation therapy in patients with pelvic neoplasms. 2-Amino-ethylisothiouronium (AET) is a radiation-protective agent when given systemically but absorbs poorly from the intestines. Accordingly, it was explored for the local protection of the bowel and bladder during radiation to the pelvis. Radiation localized to the pelvis in various high fractionated doses and various schedules was applied to pairs of stumptailed monkeys (Macaca arctoides): one was always a control; and the other was treated with AET. AET was applied to the bladder through a catheter and to the rectum with a cotton tampon during the time of radiation. After radiation, AET was removed by repeated washings. Control animals developed hemorrhage, diarrhea, and emaciation and died at various times after completion of the radiation course; biopsy of rectal mucosa showed severe radiation damage. AET-treated animals had only occult blood in the stools and suffered slight weight loss; rectal biopsies showed normal tissues 2 weeks after radiation.

LNCaP model of human prostatic carcinoma.

The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) human male karyotype with several marker chromosomes. The malignant properties of LNCaP cells are maintained. Athymic nude mice develop tumors at the injection site (volume-doubling time, 86 hr). Functional differentiation is preserved; both cultures and tumor produce acid phosphatase. High-affinity specific androgen receptors are present in the cytosol and nuclear fractions of cells in culture and in tumors. Estrogen receptors are demonstrable in the cytosol. The model is hormonally responsive. In vitro, 5 alpha-dihydrotestosterone modulates cell growth and stimulates acid phosphatase production. In vivo, the frequency of tumor development and the mean time of tumor appearance are significantly different for either sex. Male mice develop tumors earlier and at a greater frequency than do females. Hormonal manipulations show that, regardless of sex, the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender of hormonal status of the host.

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.

Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents.

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.

Factors affecting immune responsiveness in vitro of germfree allogeneic radiation chimeras. I. Differences between donor and host strains.

An important aspect of bone marrow transplantation has been focused upon. It has been demonstrated that significant differences between in vitro responses of germfree DBA/2 mice (donor strain) and of C3H/He (recipient strain) exist. The PHA response of spleen cells from germfree C3H/He mice is greater than that of DBA/2 mice. However, the reverse is true in regard to Con A responsiveness. In fact, calculation of a Con A/PHA ratio reveals a striking difference between strains. B cell reactivity as assessed by LPS mitogenic responsiveness is similar in both strains. The cell mediated responsiveness of DBA/2 mice is also diminished as measured by mixed lymphocyte reaction and cell mediated cytotoxicity. An inverse correlation between plaque forming cell (PFC) responses in vitro and the Con A/PHA ratio in DBA/2 mice is suggestive of a predominance of inherent suppressor cell activity in this strain. These characteristics of the DBA/2 immune responsiveness may be a factor in the apparent T cell unresponsiveness seen in DBA/2 leads to C3H/He mouse allogeneic bone marrow chimeras.

Depletion of phenylalanine in the blood of phenylketonuric patients using a PAL-enzyme reactor. An in vitro study.

Blood samples obtained from eight adult phenylketonuric individuals had a mean phenylalanine level of 25 mg/dl. When these samples were circulated through multitubular enzyme-reactors prepared with immobilized phenylalanine ammonia lyase an average of 77% of phenylalanine was metabolized within 30 minutes. We conclude that phenylalanine in human phenylketonuric blood is just as susceptible to metabolism by PAL-enzyme reactors as phenylalanine that is added to normal blood, or that is circulating in dogs and monkeys made hyperphenylalaninemic by experimental means.

Inhibition of Friend virus (FVP)-induced murine erythropoiesis with prostaglandin (PGF2 alpha): potentiation and inhibition of erythropoietin and prevention of both with PGD2.

An erythropoietin-independent virus-induced murine erythroleukemia (FVP) is used to compare the effects of an erythropoiesis inhibitory factor (EIF) isolated from human urine with the effects of prostaglandin F2 alpha. The consequent inhibition of FVP-induced erythropoiesis suggests that EIF and PGF2 alpha have similar effects on the FVP-induced erythropoiesis in mice, and the effect of PGF2 alpha is indirect. The similarity of the actions of EIF and PGF2 alpha may indicate a potential role for prostaglandins in the physiological control of some types of erythrocytosis.