The Upper Midwest Health Study: a case-control study of primary intracranial gliomas in farm and rural residents.

Since several studies indicated that farmers and agricultural workers had an excess risk of brain cancer, the National Institute for Occupational Safety and Health initiated the Upper Midwest Health Study to examine risk of intracranial glioma in the non-metropolitan population. This population-based, case-control study evaluated associations between gliomas and rural and farm exposures among adults (ages 18 to 80) in four upper midwestern states (Iowa, Michigan, Minnesota, Wisconsin). At diagnosis/selection, participants lived in non-metropolitan counties where the largest population center had fewer than 250,000 residents. Cases were diagnosed 1 January 1995 through 31 January 1997. Over 90% of 873 eligible ascertained cases and over 70% of 1670 eligible controls consented to participate. Participants and nonparticipants, evaluated for "critical questions" on main and refusant questionnaires, differed significantly in farming and occupational experience, ethnicity, education, and lifestyle. The 1,175 controls were more likely than the 798 cases to have reported ever drinking alcohol (77% vs. 73%, adjusted odds ratio (OR) 0. 73, 95% confidence interval (CI) 0.59-0.92) and having had panoramic dental x-rays (34% vs. 29%, OR 0. 75, CI 0.61-0.92). Controls spent a greater percentage of their lives in non-metropolitan counties (78% vs. 75%, OR 0.81, CI 0.67-1.09). Among ever-farmers, controls were more likely to have had exposure to farm insecticides (57% vs. 50%, OR 0.75, CI 0.59-0.95) and farm animals (96% vs. 91%, OR 0.48, CI 0.25-0.90). Moving to a farm as an adolescent (ages 11 to 20) vs. as an adult was associated with a greater risk of glioma. In our study sample, farm or rural residence and summary farm exposures were associated with decreased glioma risk. However, nonparticipation by never-farming eligible controls could have affected results. Comparisons of farm chemical exposures may clarify associations between farming and glioma that others have reported.

Lessons learned: geographic information systems and farmworkers in the Lake States.

Agencies serving the estimated 42,000 to 137,000 migrant and seasonal farmworkers in the Lake States (Wisconsin, Michigan, and Minnesota) face distinct challenges, including inadequate access to farmworker data to address their needs. This project developed and evaluated a geographical information system (GIS) database for compiling and displaying existing farmworker data in the Lake States. A three-step study was conducted in the Lake States: (1) a preliminary resource and needs assessment was conducted among agencies serving farmworkers, (2) a GIS product was created using data available from state agencies, and (3) the GIS product was evaluated by an advisory board of qualified occupational health and safety representatives for appropriateness, applications, and ease of use. Agencies participated by sharing their available farmworker data. The GIS product consisted of a CD-ROM with data displayed in a graphic format and downloadable spreadsheet files consolidated by county demographic, crop, housing, and migrant health clinic information. Evaluators of the GIS product found it to be an accessible, unique clearinghouse for farmworker-related data. The GIS product can become a valuable tool for agencies serving farmworkers and those researching farmworker-related issues. Agencies and health professionals require useful and comprehensive databases to track and serve farmworkers, and a multi-agency partnership using GIS technology could provide this capability. Further research is required with improved definitions and resources to apply the GIS product.

Expression and initial promoter characterization of PCAN1 in retinal tissue and prostate cell lines.

Prostate cancer is the most frequently diagnosed neoplasia in men and one of the leading causes of cancer-related deaths in men over 60. In an effort to understand the molecular events leading to prostate cancer, we have identified PCAN1 (prostate cancer gene 1) (also known as GDEP), a gene that is highly expressed in prostate epithelial tissue and frequently mutated in prostate tumors. Here we demonstrate its expression in neural retina, and retinoblastoma cell culture but not retinal pigment epithelial cell culture. We further characterize PCAN1 expression in the prostate cell lines RWPE1, RWPE2, and LnCAP FGC. We demonstrate an increase in expression when the cells are grown in the presence of Matrigel, an artificial extracellular basement membrane. Expression was time dependent, with expression observed on d 6 and little or no expression on d 12. Testosterone was not found to increase PCAN1 expression in this culture system. In addition, normal prostate epithelial cells co-cultured with normal prostate stromal cells did not exhibit PCAN1 expression at any time. To definitively locate the transcription initiation sites, we performed restriction-ligase-mediated 5' RACE, to selectively amplify only mRNA with a 5' cap. An initial characterization of the sequence upstream of the initiation sites determined six possible binding sites for the prostate specific regulatory protein NKX3.1 and four potential binding sites for the PPAR/RXR heterodimer that is involved in the control of cell differentiation and apoptosis.

Genetics of prostate cancer.

Prostate cancer is the most frequently diagnosed visceral cancer of men, responsible for approximately 40,000 deaths in adult males per year. To identify the genetic causes of prostate cancer, we performed a whole genome scan of affected sib pairs, using DNA markers spaced evenly across the human genome. We demonstrated that regions on chromosomes 1, 4, 5, 7, 8, 11, 16 and 19 might harbor genes that predispose individuals to prostate cancer and may affect tumor growth rate and tumor aggressiveness. Here we present DNA sequence analysis of KIAA 0872 and 17-beta hydroxysteroid dehydrogenase that are located on chromosome 16 within the mapped region, and we demonstrate that neither of these genes carries mutations in the protein coding region or their splice junction sites. These results suggest that these genes are less likely to be associated with the cause of familial prostate cancer.

Identification of a gene frequently mutated in prostate tumors.

Although prostate cancer is the second leading cause of cancer death for men in the United States, the genetics of tumor development are poorly understood. Several expressed sequence tagged genes (ESTs) that are expressed predominantly in the prostate have recently been identified, although their role in the development and maintenance of the prostate is unknown. Here, we demonstrate that the gene identified as UNIGENE cluster Hs. 104215, which codes for a message found predominantly in the prostate, may be important in tumor development. We name this gene PCan1 for Prostate Cancer gene 1. Northern blot experiments were performed using RNA isolated from tumor-derived cell lines and human prostate to determine the expression pattern of the gene. DNA sequencing was used to identify mutations that occurred in tumor tissue. By Northern blot analysis, this gene product was not detectable in LNCaP, DU 145, or PC-3 prostate cancer cell lines, although it was readily observed in RNA isolated from total prostate and from dissected central and peripheral regions of prostate. Sequence analysis of genomic DNA from LNCaP, DU 145, or PC-3 cells demonstrated a G/A polymorphism at position 193. Analysis of matched tumor-derived DNA and blood-derived DNA samples from 11 of 13 patients who had undergone a radical prostatectomy and who were homozygous for A in blood-derived DNA demonstrated mutation of position 193 in matched tumor samples resulting in G/A polymorphism. Sixteen additional patient samples were G/A polymorphic in both blood-derived DNA and tumor-derived DNA and two samples were GG in both blood-derived and tumor-derived DNA. Our results suggest that this gene may be a hot spot for mutation in prostate cancer, especially because our radiation hybrid mapping located this gene within a region identified in linkage mapping studies of affected families with prostate cancer. Loss of heterozygosity in prostate tumors has also been reported at the location of PCan1. Further studies to determine the functional role of this candidate tumor suppressor gene are warranted.

Influence of patient preferences and local health system characteristics on the place of death. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Risks and Outcomes of Treatment.

OBJECTIVE: To examine the degree to which variation in place of death is explained by differences in the characteristics of patients, including preferences for dying at home, and by differences in the characteristics of local health systems. DESIGN: We drew on a clinically rich database to carry out a prospective study using data from the observational phase of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT component). We used administrative databases for the Medicare program to carry out a national cross-sectional analysis of Medicare enrollees place of death (Medicare component). SETTING: Five teaching hospitals (SUPPORT); All U.S. Hospital Referral Regions (Medicare). STUDY POPULATIONS: Patients dying after the enrollment hospitalization in the observational phase of SUPPORT for whom place of death and preferences were known. Medicare beneficiaries who died in 1992 or 1993. MAIN OUTCOME MEASURES: Place of death (hospital vs non-hospital). RESULTS: In SUPPORT, most patients expressed a preference for dying at home, yet most died in the hospital. The percent of SUPPORT patients dying in-hospital varied by greater than 2-fold across the five SUPPORT sites (29 to 66%). For Medicare beneficiaries, the percent dying in-hospital varied from 23 to 54% across U.S. Hospital Referral Regions (HRRs). In SUPPORT, variations in place of death across site were not explained by sociodemographic or clinical characteristics or patient preferences. Patient level (SUPPORT) and national cross-sectional (Medicare) multivariate models gave consistent results. The risk of in-hospital death was increased for residents of regions with greater hospital bed availability and use; the risk of in-hospital death was decreased in regions with greater nursing home and hospice availability and use. Measures of hospital bed availability and use were the most powerful predictors of place of death across HRRs. CONCLUSIONS: Whether people die in the hospital or not is powerfully influenced by characteristics of the local health system but not by patient preferences or other patient characteristics. These findings may explain the failure of the SUPPORT intervention to alter care patterns for seriously ill and dying patients. Reforming the care of dying patients may require modification of local resource availability and provider routines.

Cancer screening and prevention in rural Wisconsin: the Greater Marshfield Experience.

BACKGROUND: Providing medical services to rural residents results in unique challenges to providers and patients. Cancer screening (CS) and early detection services (EDS) are frequently underutilized with rural residents often presenting with advanced cancer at diagnosis. A comprehensive approach to determine barriers and overcome them constitutes "The Greater Marshfield Experience." METHODS: Focus groups with rural residents determined the greatest barriers to receipt of CS and EDS were distance, cost, time from work and self-reliant behavior. Directives to address these concerns were to keep information simple and provide services at the workplace. In response, Marshfield Clinic and its research division developed a collaborative research partnership with public health agencies (PHA), federally funded government programs and volunteer agencies. RESULTS: In-house activities to remove barriers for providing CS and EDS included the development of a separate screening unit for these activities. Reminder systems were employed to notify patients of the need and availability of preventative services. Co-payments for health screening services were eliminated from the clinic owned health plan. Area residents near poverty level were encouraged to enroll in federally subsidized health plans that promoted and paid for CS and EDS. Federally funded cancer screening studies were implemented that funded breast and cervical cancer screening and evaluated the benefits of screening for prostate, lung, colorectal and ovarian cancers (PLCO). Outreach activities included developing partnerships with local PHA and minority groups and providing mobile screening services to remote areas. CONCLUSION: Concentrated, collaborative efforts to develop in-house systems and outreach activities resulted in delivery of CS and EDS in remote areas.

Seriously ill hospitalized adults: do we spend less on older patients? Support Investigators. Study to Understand Prognoses and Preference for Outcomes and Risks of Treatments.

OBJECTIVE: To determine the effect of age on hospital resource use for seriously ill adults, and to explore whether age-related differences in resource use are explained by patients' severity of illness and preferences for life-extending care. STUDY DESIGN: Prospective cohort study. SETTING: Five geographically diverse academic acute care medical centers participating in the SUPPORT Project. PATIENTS: A total of 4301 hospitalized adults with at least one of nine serious illnesses associated with an average 6-month mortality of 50%. MEASUREMENTS: Resource utilization was measured using a modified version of the Therapeutic Intervention Scoring System (TISS); the performance of three invasive procedures (major surgery, dialysis, and right heart catheter placement); and estimated hospital costs. RESULTS: The median patient age was 65; 43% were female, and 48% died within 6 months. After adjustment for severity of illness, prior functional status, and study site, when compared with patients younger than 50, patients 80 years or older were less likely to undergo major surgery (adjusted odds ratio .46), dialysis (.19), and right heart catheter placement (.59) and had median TISS scores and estimated hospital costs that were 3.4 points and $ 71.61 lower, respectively. These differences persisted after further adjustment for patients' preferences for life-extending care. CONCLUSIONS: Compared with similar younger patients, seriously ill older patients receive fewer invasive procedures and hospital care that is less resource-intensive and less costly. This preferential allocation of hospital services to younger patients is not based on differences in patients' severity of illness or general preferences for life-extending care.

Teens teach skin cancer prevention.

Cumulative sun exposure has been linked to about 95 percent of all skin cancers. Farmers and their families, by nature of their occupations, are exposed to an abundance of sun over a long period of time and, therefore, are at an increased risk for skin cancer. Because education is known to be a primary means of health, Future Farmers of America (FFA) peer facilitators (teen educators) provided third graders in rural communities sun protection education with the hope that the message would reach the entire family. The FFA facilitators (n = 217) from 39 FFA organizations throughout Wisconsin were trained with skin cancer and sun protection information. The FFA facilitators then gave presentations on sun protection to third graders (n = 2,007) in their school districts. Control schools included 57 facilitators and 669 third graders. Evaluation involved pre-, post-, and six-month follow-up surveys testing knowledge gained by the third graders. Students who correctly responded to a question on the post-survey after incorrectly answering it on the pre-survey were said to have had a knowledge gain for that question. By using chi-square tests, the intervention group demonstrated a statistically significant (P < 0.001) higher proportion of students experiencing knowledge gain than did the control group from pre- to post-surveys for nine of the 10 questions. Summary statistics were used to describe the study population. In addition to skin cancer knowledge questions, the survey of facilitators included sun protection behavior and attitude questions. This intervention was able to use peer educators as instructors to demonstrate knowledge gain in the youths of the target population. The pilot project materials costs were +0.55 per third grade student and +3.50 per facilitator. Using a school-based organization such as FFA provided a cost-effective means of reaching the rural population.

Results of a rural breast health education demonstration project.

The Healthy People 2000-National Health Promotion and Disease Prevention Objectives call for an increase in breast health education to the public to increase women's knowledge about breast cancer and the benefits of screening. A breast health outreach education intervention for community health professionals was designed, implemented, and evaluated. The barriers to continuing education of health professionals of rural areas were addressed. Low-cost, county-based seminars using a comprehensive breast health education curriculum were provided for community health professionals. The intervention demonstrated an increase in a professional's knowledge about breast cancer and breast cancer screening, and an increase in their breast self-examination skills. Six months after intervention, community health professionals reported an increase in the frequency of their breast self-examination performance.

The treatment of older adult patients with acute myeloid leukemia by triple infusion chemotherapy.

Adult patients (> or = 56 years old) with acute myeloid leukemia (AML) received induction therapy consisting of daunorubicin (60 mg/m2), etoposide (80 mg/m2), and cytarabine (200 mg/m2) daily for 5 days by continuous i.v. infusion (120 hours). The initial protocol was modified so that patients who were not hypoplastic after the first cycle of chemotherapy received a second cycle of treatment, utilizing 30 mg/m2 of daunorubicin/24 hours for 5 days plus etoposide and cytarabine as used in the first cycle. Two courses of consolidation with etoposide and cytarabine at the same dose and schedule were given. Patients were then maintained on cytarabine monthly. Twelve of 29 previously untreated patients (41%) achieved complete remission (CR). Excluding patients with secondary AML, 48% of all patients (11/23) achieved CR, including 56% > or = 70 years old. The median duration of CR was 41 weeks and median survival of CR patients was 54 weeks. Six of 13 patients (46%) with relapsed AML achieved CR. Toxicity in these older adult patients has been mild. Two patients (8%) had severe mucositis and one had severe (bloody) diarrhea. Most patients developed a mild transient asymptomatic rash. Triple infusion chemotherapy (TIC) may be as effective as other chemotherapy regimens for AML in older adults and has acceptable toxicity.

Skin cancer prevention: a peer education model.

Results from a quasi-experimental project indicate that skin cancer prevention and sun protection education can successfully be promoted by using peer educators. Senior high students (40) facilitated and taught a sun protection curriculum to third-grade students (508) enrolled at the experimental sites. The curriculum's effects were assessed with pre-program, post-program, and 6-month follow-up survey-instruments. The experimental sites using high school (peer) facilitators were effective in conveying knowledge to younger students based on knowledge gained on the post-program surveys. Overall, the intervention group demonstrated a mean improvement of 3.4 questions on the post-program survey, while the control group improved 0.1 questions (p < 0.01). Additional benefits included a knowledge gain by the peer facilitators, a self-reported possible increase in desired behavior change, and an improved attitude about sun protection. Implications for pediatric clinical practice are noted.

Health education delivery by Wisconsin veterinarians.

Established methods of health promotion for the general population are not as effective with rural populations, in part because conventional health education delivery systems may not penetrate isolated rural areas. In particular, the self-reliant behaviors of farmers make them less likely to seek traditional forms of health care, including health promotional activity. Yet farmers place a great deal of trust in their veterinarian and highly rate veterinarian integrity. Wisconsin veterinarians expressed an interest in the health of their human clients as well as the health of the animals in their care. An education demonstration project was developed to determine farmers' acceptance of veterinarians delivering human health information to their workplace (farms). Thirteen veterinarians who provide services in one north central Wisconsin county delivered skin cancer and sun protection information to farmers as part of their routine herd health checks. Participating farmers reported this to be an acceptable way to receive information about human health issues. This novel method of education delivery may be an effective means to disseminate human health information to difficult-to-reach rural populations.

Cancer education interventions for rural populations.

To respond to major needs expressed by 15 farm family focus group participants, education interventions were designed to overcome barriers to primary prevention for skin cancer. Farmers are at high risk for developing skin cancer because of occupational exposure. In an attempt to increase skin cancer prevention education in a rural population, three demonstration projects were developed and field tested. Projects were designed to overcome barriers defined by the focus groups. One project evaluated a school-based education intervention. A second project evaluated a family-based education intervention. Knowledge gain was the evaluation endpoint of these two projects. Significant knowledge gain was demonstrated for these projects. A third project was designed to deliver skin cancer information directly to farmers using veterinarians. Farmers found this method of delivery acceptable.

Hematopoietic growth factors. A promising future for use in bone marrow dysfunction.

The clinical future of hematopoietic growth factors appears promising. They will probably achieve broad clinical application in a wide variety of hematologic disorders. Their use in infectious diseases associated with granulocytopenia and in cancer-treatment regimens as adjuvant agents against myelosuppression and perhaps as stimulants of the natural anti-cancer effects of host cells also seems appropriate.