Ethical and practical implications of the human genome initiative for family medicine.

Major advances in predictive genetic testing resulting from the Human Genome Initiative could change significantly the routine practice of family medicine. Family physicians should be aware that increased genetic information may affect patients' abilities to acquire and maintain insurance and employment and that interested parties will have incentives to seek this information. The social consequences of genetic information, as well as increased health promotion efforts, may raise problems of informed consent and confidentiality. In addition to their ethical implications, these developments will also affect the practice of family physicians in practical ways such as record keeping. We discuss cases that illustrate the potential impact of these emerging technologies on the practice of family medicine.

Insurance and genetic testing: where are we now?

Basic research will spur development of genetic tests that are capable of presymptomatic prediction of disease, disability, and premature death in presently asymptomatic individuals. Concerns have been expressed about potential harms related to the use of genetic test results, especially loss of confidentiality, eugenics, and discrimination. Existing laws and administrative policies may not be sufficient to assure that genetic information is used fairly. To provide factual information and conceptual principles upon which sound social policy can be based, the Human Genome Initiative established an Ethical, Legal, and Social Issues Program. Among the first areas to be identified as a priority for study was insurance. This paper provides a review of life, health, and disability insurance systems, including basic principles, risk classification, and market and regulatory issues, and examines the potential impact of genetic information on the insurance industry.

Metastasis of unknown origin.

Evaluation of the patient with metastasis of unknown origin should be structured to quickly identify treatable tumors or the need for palliation while avoiding prolonged hospital stays and testing that will result in neither improved treatment nor better prognosis. The evaluation should be symptom-directed and pathologically oriented. It is the responsibility of the family physician in caring for a patient with MUO to ensure that communication is facilitated between surgeon, oncologist, pathologist, and patient. The physical examination should include thyroid, breasts, pelvic, and rectal examinations. General lab analyses should include fecal occult blood testing, complete blood count, urinalysis, serum calcium, and liver function studies. Men should have assays for prostate-specific antigen and serum prostatic acid phosphatase. Women should undergo mammography and pelvic ultrasound. Undifferentiated carcinoma is likely to originate from either small cell bronchogenic, lymphoma, or germ cell, and thus, serum should be assayed for HCG and AFP. Further radiologic studies, in the absence of specific symptoms, should be limited to chest radiographs and abdominal CT. Contrast studies should be included only if there is organ dysfunction. Biopsy of the malignant tissue should be done early, and studies should include histochemistry, immunohistology, and electron microscopy. Tissues from female patients should be studied for estrogen and progesterone receptors. When a biopsy is planned, advance communication between the family physician or surgeon and the pathologist greatly increases the chance of identifying a primary site. It is important that the surgeon obtain sufficient material to enable study, not only by standard histologic techniques, but also by electron microscopy, special stains, estrogen receptor activity, hormonal markers, and tumor markers. Treatment of patients for whom a primary tumor remains undiscovered must include toxic therapies only for those with good functional status who are likely to respond. Therapy must be pursued for palliation of symptoms when they develop. As physicians, we must control the urge to do something at those times when doing nothing is more appropriate. We must provide continuous support for both the patient and family, protecting to the best of our ability their quality of life. A physician should never convey the impression that it is "not cost-effective" to look for the source of a patient's malignancy. It can be emphasized that further search for a primary tumor carries both medical risk and expense, yet is unlikely to locate the primary tumor or improve the response to therapy or the quality of life.(ABSTRACT TRUNCATED AT 400 WORDS)

Legal issues in managing breast disease.

The impact of legal issues in breast cancer care reflects the significance of breast cancer as a health concern of women. Breast cancer has emerged as a leading liability risk for primary care physicians, with most cases focusing on delayed diagnosis. Although the clinical impact of delayed diagnosis of breast cancer is often controversial, physicians should strive to diagnose breast cancer as early as possible in the natural history of the disease. No currently available data suggest that a delay of less than 2 months between the onset of symptoms and diagnosis or treatment adversely influences outcome. Techniques that help physicians reduce the liability risks associated with breast cancer care include patient education, adequate documentation and follow-up, and referral or consultation in high-risk situations.

Screening for gynecologic cancer. Vulvar, vaginal, endometrial, and ovarian neoplasms.

The success of the Pap smear in screening for cervical cancer illustrates many of the tenets of screening for disease. Unfortunately, no other gynecologic malignancy shares this success. Detection of most gynecologic malignancies occurs once they have become symptomatic and on clinical examination at the interval cancer-related checkup as recommended by the ACS. These examinations, done yearly in women older than 40 and every 3 years in younger women, can go a long way in the detection of genital tract disease. In detecting vulvar neoplasms, visual inspection of the entire perineum coupled with palpation to include Bartholin's glands and early biopsy of suspicious vulvar lesions promotes earlier diagnosis. Self-examination similar to breast self-examination and increased patient awareness are potential education goals for physicians as well as cancer and medical societies. Vaginal examination at the cancer checkup should continue. The finding that most vaginal cancers are picked up by abnormal cytology while they are still asymptomatic argues strongly for Pap testing after menopause. The knowledge that women who are status posthysterectomy for benign disease are not protected from developing vaginal cancers mandates continued Pap testing in this population as well. Because endometrial cancer is common, primary care physicians should maintain a high index of suspicion. Aspiration biopsy is a simple office-based procedure with low risk and good yield, and any woman in the perimenopausal and postmenopausal period who presents with atypical bleeding patterns should be evaluated. Although not recommended as a general screening test, the ACS does advocate endometrial sampling in the high risk woman at the time of menopause. The greatest challenge to primary care physicians may be the early detection of ovarian cancer. No single test is available, nor is any advocated in screening for this lethal disease. Currently, only periodic physical examination is recommended at the cancer checkup interval. Ultrasound, both transabdominal and transvaginal, may help in detecting adnexal masses, but is not sensitive enough to differentiate benign from malignant lesions. In this setting, and in the patient with suspected ovarian cancer, CA 125 and AFP may be helpful in determining which patients require surgical exploration. Women with positive family histories for ovarian cancer require greater vigilance and close follow-up with serial ultrasound and CA 125 determinations. As the population ages, cancer, which is primarily a disease of age, will continue to increase in incidence.(ABSTRACT TRUNCATED AT 400 WORDS)

Cervical cancer screening. Past success and future challenge.

Population screening for cervical cancer resulted in significant reduction in the morbidity and mortality from cervical cancer. An increased understanding of the relationship of HPV infection with cervical cancer and the natural history of cervical cancer precursor lesions further solidifies and expands the biological basis for cervical cancer screening. Pap tests in asymptomatic women remain the cornerstone of cervical cancer screening. Clinicians should be cognizant of the significant false-negative rate of Pap smears. Meticulous attention to proper Pap smear technique is necessary to maximize the sensitivity of the test. Further research is needed to establish the role of cervicography and HPV DNA hybridization techniques in cervical cancer screening.

Chloride transport in Anacystis nidulans.

Anacystis nidulans will take up and accumulate chloride ions. When the external concentration was 0.2 mM Cl(-) the level in the cells was 2.8 mM Cl(-) and under these conditions the flux across the cell surface was in the region of 10(-13)equiv Cl(-)·sec(-1)·cm(-2). It is suggested that this Cl(-) influx is active and operates against an electrochemical potential gradient estimated to be 117 mV or 2.68 kcal/mole. The uptake of (36)Cl was inhibited by low temperatures and there was a net loss of Cl(-) from the cells with the level decreasing towards the equilibrium value as estimated from K(+) distribution. Although the active influx of Cl(-) was often stimulated by light this was not always the case. Dark storage treatment and regulation of the chlorophyll a/phycocyanin ratios as well as total pigment content of the cells did not clarify the conditions which brought about light stimulation. Moreover, the metabolic inhibitors CCCP and CMU and also the use of anaerobic conditions did not clearly indicate the relationship between the influx mechanism and light-dark metabolism and no firm conclusions could be made about the nature of the energy source. The variation in the degree of light stimulation probably reflects the fact that in this procaryotic organism the photosynthetic and respiratory units are located on the same membrane systems and are in very close proximity to the probable site of the Cl(-) pump, the plasmalemma.

Cation regulation in Anacystis nidulans.

Anacystis nidulans accumulates K(+) in preference to Na(+). The majority of the internal K(+) exchanges with (42)K by a first order process at rates of about 1.3 pequiv·cm(-2)·sec(-1) in the light and 0.26 pequiv·cm(-2)·sec(-1) in the dark. Although the K(+)/K(+) exchange was stimulated by light and inhibited by 10(-4) M CCCP and 10(-5) M DCMU there are several indications that this cation is passively distributed in Anacystis. Inhibition of the exchange by CCCP and DCMU occurred at concentrations greater than those required to inhibit photosynthesis and the K(+) fluxes were stimulated by low temperatures. Moreover, although valinomycin stimulated the exchange this compound did not induce a net K(+) leak. Assuming K(+) is passively distributed and in free solution within the cytoplasm, as indicated by osmotic studies, would imply that there is an active Na(+) extrusion pump operating in this organism. As yet there are no firm conclusions about the nature of the energy source for this efflux pump.