BAG-1 expression in normal and neoplastic endometrium.

OBJECTIVE: BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors. High levels of BAG-1 have been implicated as a prognostic indicator in breast cancer. Whether this observation can be generalized to endometrial cancer remains unknown. METHODS: IRB permission was obtained for use of human discarded tissue. Immunohistochemical analyses were performed on: proliferative endometrium (PEM, 6), secretory endometrium (SEM, 28), "low-grade" neoplastic lesions (complex atypical hyperplasia and grade 1 endometrial adenocarcinomas) (19), and "high-grade" cancers (grade 2 and 3 endometrial adenocarcinomas) (13). The level of total BAG-1 and its isoforms was evaluated by Western blot in lysates from Ishikawa cells (grade 1), MFE 296 cells (grade 2), and SK-UT(2) cells (grade 3). RESULTS: The proportion of "high-grade" cancers with positive cytoplasmic staining for BAG-1 was higher than that of secretory endometrium (P = 0.006). Additionally, the proportion of specimens with positive staining for nuclear BAG-1 expression was significantly higher among high-grade carcinoma specimens compared to secretory specimens (P = 0.009). A high proportion (91%) of all specimens were positive for BCL-2, limiting the ability to subcategorize the other variables analyzed. There was no relationship between positive nuclear BAG-1 expression and either estrogen receptor (ER) or progesterone receptor (PR) expression. BAG-1 was expressed in the three cell lines evaluated and total BAG-1 level was not different among the different cell lines. CONCLUSION: BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis.

Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests.

BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS: One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS: Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.

Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA.

OBJECTIVES: To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS: 239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS: An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS: Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

Advanced practice issues: results of the ONS Advanced Practice Nursing survey.

PURPOSE/OBJECTIVES: To ascertain the critical issues in current advanced practice nurse (APN) roles in oncology. DESIGN: Descriptive. SETTING: National. SAMPLE: 368 Oncology Nursing Society (ONS) APNs in oncology practice. METHODS: Subjects completed an 11-page self-administered questionnaire comprised of 62 multiple-choice and open-ended questions. Subjects were asked to identify level of importance for ONS to address selected issues in each section. MAIN RESEARCH VARIABLES: Demographic information and APN issues regarding practice, outcomes, prescriptive authority, reimbursement, education, continuing education, licensure and certification, legislation, and challenges facing oncology APNs. FINDINGS: The majority of APNs were nurse practitioners working in a hematology/oncology practice in an urban setting providing direct patient care. Priority practice issues were lack of agreement among state boards of nursing related to privileges, lack of understanding of the role by patients and healthcare professionals, and lack of an APN definition. Important APN outcomes were symptom management, quality of life, patient/family satisfaction, and cost of care. Priority educational topics were oncology disease management, pharmacology, advanced physical assessment, and reimbursement. Challenges facing oncology APNs were lack of an APN definition, reimbursement issues, documentation of outcomes, prescriptive authority, variance in education, merging of current roles, certification, loss of cancer specialty, and second licensure. CONCLUSIONS: Numerous APN issues continue to be unresolved. APN outcomes research is needed to validate the oncology APN role in cancer care. IMPLICATIONS FOR NURSING PRACTICE: Survey results and specific recommendations have been forwarded to the ONS Steering Council and Board of Directors for implementation decisions.

Development of a home-based family caregiver cancer education program.

INTRODUCTION: This article describes a home-based educational program developed specifically for family caregivers of cancer patients who receive hospice and home care. The overall aim of this educational program is to specifically address family caregivers' needs for acquisition of necessary knowledge and skills to meet the physical and psychosocial demands associated with caring for a patient with advanced cancer. PROGRAM DEVELOPMENT: Originally, components of this program were offered in a small group discussion format within hospital and community settings. The educational program was transformed to accommodate the unique needs and constraints of homebound family caregivers who have very limited time and/or opportunities for support and education outside of the home. The program is comprised of educational modules that provide hospice and home care professionals with written and audiovisual materials designed to facilitate brief, structured, educational encounters with family caregivers in the home setting. DISCUSSION: Two hundred thirty-seven educational module kits were distributed to professionals affiliated with twenty-four home care and hospice agencies in the Greater Philadelphia area. Results of a telephone survey designed to elicit evaluation data from professional staff members who had used the educational modules are presented. Limitations, plans for future program evaluation, cost implications, and implementation recommendations related to this educational program are described.

Apoptosis during bone-like tissue development in vitro.

We present evidence of cell death by apoptosis during the development of bone-like tissue formation in vitro. Fetal rat calvaria-derived osteoblasts differentiate in vitro, progressing through three stages of maturation: a proliferation period, a matrix maturation period when growth is downregulated and expression of the bone cell phenotype is induced, and a third mineralization stage marked by the expression of bone-specific genes. Here we show for the first time that cells differentiating to the mature bone cell phenotype undergo programmed cell death and express genes regulating apoptosis. Culture conditions that modify expression of the osteoblast phenotype simultaneously modify the incidence of apoptosis. Cell death by apoptosis is directly demonstrated by visualization of degraded DNA into oligonucleosomal fragments after gel electrophoresis. Bcl-XL, an inhibitor of apoptosis, and Bax, which can accelerate apoptosis, are expressed at maximal levels 24 h after initial isolation of the cells and again after day 25 in heavily mineralized bone tissue nodules. Bcl-2 is expressed in a reciprocal manner to its related gene product Bcl-XL with the highest levels observed during the early post-proliferative stages of osteoblast maturation. Expression of p53, c-fos, and the interferon regulatory factors IRF-1 and IRF-2, but not cdc2 or cdk, were also induced in mineralized bone nodules. The upregulation of Msx-2 in association with apoptosis is consistent with its in vivo expression during embryogenesis in areas that will undergo programmed cell death. We propose that cell death by apoptosis is a fundamental component of osteoblast differentiation that contributes to maintaining tissue organization.

Ifosfamide. Patient care management.

Ifosfamide is an antineoplastic drug with efficacy and activity in numerous cancers. This drug can be administered safely in a hospital setting if toxicities and side effects are monitored frequently by a well-informed and educated nursing staff. Problems may occur in any bodily system, such as the kidney, central nervous system (CNS), gastrointestinal tract, and bone marrow. This article reviews appropriate ways to monitor for complications and plan correct nursing interventions. Ifosfamide (Ifex, Mead Johnson) is an alkylating agent that is not cell cycle specific. One of its metabolites, acrolein, is responsible for hematuria. Concurrent administration of mesna (Mesnex, Mead Johnson) is used to prevent this complication. The metabolite chloroacetaldehyde may be responsible for CNS toxicities. When kidney function and electrolytes are within normal limits and psychotropic medications are not given concomitantly, this rarely occurs. Gastrointestinal toxicities are usually not severe, but may include occasional nausea and vomiting. Hematologic toxicity includes platelet-sparing myelosuppression, which can be successfully supported with the administration of growth factors.

Methotrexate associated Peyronie's disease in the treatment of rheumatoid arthritis.

We describe two patients with rheumatoid arthritis treated with methotrexate (MTX) who developed Peyronie's disease during the course of their treatment. In one of the patients the penile fibrosis resolved on stopping the drug. The other patient's penile fibrosis partially resolved on stopping the drug. We suggest that Peyronie's disease can be a side-effect of MTX in the treatment of rheumatoid arthritis.

Hormonal regulation of cell death in rabbit uterine epithelium.

It is known that estrogen (E) and progesterone (P) play important roles in the regulation of endometrial growth. In the rabbit endometrial epithelium, a balance is maintained between cell proliferation and cell death which seems to be under ovarian hormonal control. In this study the authors determined cell proliferation by quantitating the mitotic index (MI) and cell death by quantitating the death index (DI) in uterine histologic sections from whole animals that were hormone treated versus control rabbits. E caused proliferation of uterine epithelial cells and decreased the DI transiently, while P also increased proliferation but decreased the DI dramatically. In a time course study, after a single injection of human chorionic gonadotropin to induce pseudopregnancy, there was transient decrease in the DI and an increase in the MI between Days 2 and 5. In pseudopregnant animals, hormones had no effect in intact animals, but after ovariectomy there was about a 124-fold increase in the DI, which could be prevented by P administration. The predominant type of cell death observed in this system is apoptosis (97.5%), as opposed to necrosis (2.5%). Thus, it is proposed that cell death may be as important as cell proliferation in the regulation of normal uterine epithelial growth.

Evidence for soluble factors regulating cell death and cell proliferation in primary cultures of rabbit endometrial cells grown on collagen.

Primary cultures of rabbit endometrial cells grown on collagen substrates exhibit cyclic changes in DNA content throughout extended periods of culture. These cycles are characterized by periods of significant increases and decreases in the DNA content of the cultures or number of cells present, yet through the entire duration of culture there is no net change in the total DNA. The rates of cell proliferation and cell death change through time in culture with the same periodicity as the changes in DNA. Neither changes in the rate of cell proliferation nor the rate of cell death alone are sufficient to account for the changes in DNA. Rather, there appears to be a feedback mechanism operating between cell proliferation and cell death such that when one increases, the other increases concomitantly in order to maintain a homeostasis in total culture mass. This homeostasis appears to be mediated by a soluble cell proliferation factor (CPF) and a cell death factor (CDF) produced by the cells. CPF and CDF may be obtained from either conditioned media or cultured cell extracts. These biological activities are heat and trypsin sensitive. The major mode of cell death in these cultures appears to be apoptosis or programmed cell death, characteristic of renewing epithelia. The data suggest that this tissue culture model system represents a renewing cell population containing stem cells and their progeny, whose total growth is strictly regulated by CPF and CDF. As such, it provides a model system in which to study homeostasis and how it may be altered in hyperplasia and neoplasia, as well as its regulation by hormones.