Long-term life satisfaction in ageing women with work disability due to mental and musculoskeletal disorders.

BACKGROUND: Mental disorders (MDs) and musculoskeletal disorders (MSDs) are the major causes of global disability and increase in prevalence with age. AIMS: To support healthy ageing, we studied how work disability due to MDs or MSDs is related to life satisfaction (LS) cross-sectionally and in 5- and 10-year follow-ups among ageing women. METHODS: In the population-based OSTPRE cohort (women aged 58-67 in 1999), data on lifetime permanent work disability pensions (DPs) due to 'MDs only' (n = 337), 'MSDs only' (n = 942) and 'MDs + MSDs' (n = 212) and 'no DP' (n = 6322) until 1999 was obtained from the Finnish national register. The OSTPRE postal enquiry included a four-item life satisfaction (LS) scale (range 4-20: satisfied 4-6, intermediate 7-11, dissatisfied 12-20) at 5-year intervals, in 1999-2004 (n = 6548) and in 1999-2009 (n = 5562). RESULTS: In 1999, the risks of belonging to the dissatisfied LS group (score 12-20) vs. the satisfied group (score 4-6) were higher in 'MDs only' (OR = 4.30; 95%CI 2.95-6.28), 'MSDs only' (OR = 2.69; 2.12-3.40) and 'MDs + MSDs' (OR = 2.72; 1.77-4.16) groups than in the 'no DP' group. In the follow-ups, these risks were OR5yr = 5.59 (3.54-8.84) and OR10yr = 4.94 (2.80-8.73) for 'MDs only', OR5yr = 3.36 (2.58-4.37) and OR10yr = 3.18 (2.40-4.21) for 'MSDs only', and OR5yr = 4.70 (2.75-8.05) and OR10yr = 6.84 (3.53-13.27) for 'MDs + MSDs' (all: p ≤ 0.001). Adjusting for baseline LS did not change the pattern (all p ≤ 0.001). CONCLUSION: Work disability due to MDs and MSDs undermines healthy ageing among women via life dissatisfaction.

Technical note: Investigating the suitability of existing facilities for a new Lu-177 prostate-specific membrane antigen therapy program.

BACKGROUND: 177 Lu prostate-specific membrane antigen (PSMA) therapy prolongs survival for some prostate cancer patients. To adopt this technique, institutions may need to evaluate the suitability of existing infrastructure. PURPOSE: Develop a methodology to determine whether existing facilities can accommodate a 177 Lu-PSMA therapy program. METHODS: Room suitability is defined by both the ability to accommodate 177 Lu-PSMA therapy workflow and to provide appropriate radiation shielding. Two methods of shielding calculation were performed: (1) National Council on Radiation Protection and Measurements report 151 (NCRP-151), with workload defined in terms of the activity of 177 Lu administered, and (2) using the RadPro shielding calculator. This methodology was applied to 131 I therapy, PET-CT uptake, PET-SPECT injection, and orthovoltage therapy rooms. RESULTS: 131 I therapy rooms were found to meet both shielding and workflow requirements. The shielding was found to be adequate for orthovoltage and PET-SPECT facilities, neglecting patient transit between external washrooms. The workflow was the limiting factor for these rooms due to the requirement of dedicated washrooms that shield the patient and contain possible contamination. The PET-CT facility did not meet either criteria. The NCRP-151 method generally predicted a higher dose rate on the other side of shielding than did the RadPro calculator. The dose rate on the other side of concrete shielding as predicted by the NCRP-151 method increased relative to the dose rate predicted by the RadPro calculator as shielding thickness increased. For lead shielding, the dose rate predicted by the NCRP-151 method decreased relative to the result predicted by the RadPro calculator with increasing material thickness. CONCLUSIONS: 131 I therapy, PET-CT uptake, PET-SPECT injection, and orthovoltage therapy rooms were considered. The 131 I treatment rooms were the best candidate for 177 Lu-PSMA therapy, due to their shielding and capability to accommodate the necessary workflow.

Comorbidity of mental and musculoskeletal disorders in ageing women: A data linkage study using national registries.

BACKGROUND: Mental disorders (MDs) and musculoskeletal disorders (MSDs) are the main causes of disability. Yet, their comorbidity has not received the deserved attention. OBJECTIVE: To investigate the extent of the comorbidity between MDs and MSDs in ageing women using national registries on prescription medications and work disability pensions (DPs). METHODS: The study included 7,809 Finnish women, born during 1932-41, from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort, established in 1989. Lifetime permanent DPs due to: 1) 'MDs only' (n = 359), 2) 'MSDs only' (n = 954), 3) 'MDs + MSDs' (n = 227), were recorded till 2003. The reference group was 'no DP' (n = 6,269). Data from the OSTPRE questionnaires was obtained in 1994. Use of medications was recorded in 1995 and 2003. The use of musculoskeletal or psychotropic medications by women having a DP or medication due to MD, or MSD diagnoses, respectively, was considered as an indicator of comorbidity. RESULTS: In 1995, all DP groups had used psychotropic and musculoskeletal medications more often than the referents. Use of musculoskeletal medications was associated with a higher use of psychotropic medications, and vice versa (OR=2.45; 95% CI 2.17-2.77), compared with non-use. The 'MSDs only' group was more likely to use psychotropic (OR=1.79; 95% CI 1.50-2.12), and the 'MDs only' group musculoskeletal medications (OR=1.38; 95% CI 1.09-1.74), compared with those without DPs. The proportions of medication users were similar in 1995 and 2003; however, the amounts used increased. CONCLUSIONS: There was strong evidence for comorbidity between MDs and MSDs in ageing women. Further research concerning their longitudinal relationships is warranted.

Arthritis in adults, socioeconomic factors, and the moderating role of childhood maltreatment: cross-sectional data from the National Epidemiological Survey on Alcohol and Related Conditions.

These data present associations between socioeconomic status (SES), different types of childhood maltreatment (CM) history and family dysfunction, and arthritis in men and women across a wide age range. Arthritis was less likely among those with higher SES, regardless of CM history. INTRODUCTION: CM has been associated with increased risk of adult-onset arthritis; however, little is known about whether socioeconomic status moderates arthritis risk in those with CM history. We investigated arthritis across education, income, and race/ethnicity and whether CM moderated associations between SES and arthritis. METHODS: Data were drawn from Wave 2 (2004-2005) of the nationally representative (USA) National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n = 34,563; aged ≥ 20 years). Self-reported CM history included physical abuse, sexual abuse, emotional abuse, emotional neglect, physical neglect, and exposure to intimate partner violence (IPV). We used descriptive statistics and logistic regression to determine relationships between SES, CM, and arthritis. Interaction terms were used to test if CM moderated relationships between SES and arthritis. RESULTS: Arthritis prevalence was 21.1% (n = 3093) among men and 30.1% (n = 6167) among women. In unadjusted analyses, women (p ≤ 0.001) and older age (both sexes, p ≤ 0.01) were associated with increased odds of arthritis. All CM types were associated with increased odds of arthritis, except exposure to IPV among women. In sex-stratified, age-adjusted analyses, lower education and income, family dysfunction, being Hispanic or Asian/Native Hawaiian/Pacific Islander, and ≥ 1 physical comorbidity were associated with increased odds of arthritis among those with and without CM: trends were similar for both sexes. In age-adjusted two-way interaction terms, CM did not moderate associations between SES and arthritis. CONCLUSIONS: Although CM was associated with arthritis, associations between SES and arthritis were not amplified. Arthritis was less likely among those with higher SES, regardless of CM history.

Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities.

PURPOSE: The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer. METHODS: An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques. RESULTS: Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%). CONCLUSION: The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

Physical health comorbidities in women with personality disorder: Data from the Geelong Osteoporosis Study.

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥ 25 years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.

Is there an interaction between socioeconomic status and FRAX 10-year fracture probability determined with and without bone density measures? Data from the Geelong Osteoporosis Study of female cohort.

FRAX(©) evaluates 10-year fracture probabilities and can be calculated with and without bone mineral density (BMD). Low socioeconomic status (SES) may affect BMD, and is associated with increased fracture risk. Clinical risk factors differ by SES; however, it is unknown whether aninteraction exists between SES and FRAX determined with and without the BMD. From the Geelong Osteoporosis Study, we drew 819 females aged ≥50 years. Clinical data were collected during 1993-1997. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles. BMD was measured by dual energy X-ray absorptiometry at the same time as other clinical data were collected. Ten-year fracture probabilities were calculated using FRAX (Australia). Using multivariable regression analyses, we examined whether interactions existed between SES and 10-year probability for hip and any major osteoporotic fracture (MOF) defined by use of FRAX with and without BMD. We observed a trend for a SES * FRAX(no-BMD) interaction term for 10-year hip fracture probability (p = 0.09); however, not for MOF (p = 0.42). In women without prior fracture (n = 518), we observed a significant SES * FRAX(no-BMD) interaction term for hip fracture (p = 0.03) and MOF (p = 0.04). SES does not appear to have an interaction with 10-year fracture probabilities determined by FRAX with and without BMD in women with previous fracture; however, it does appear to exist for those without previous fracture.

Clinical consequences of changing the sliding window IMRT dose rate.

Changing pulse repetition frequency or dose rate used for IMRT treatments can alter the number of monitor units (MUs) and the time required to deliver a plan. This work was done to develop a practical picture of the magnitude of these changes. We used Varian's Eclipse Treatment Planning System to calculate the number of MUs and beam-on times for a total of 40 different treatment plans across an array of common IMRT sites including prostate/pelvis, prostate bed, head and neck, and central nervous system cancers using dose rates of 300, 400 and 600 MU/min. In general, we observed a 4%-7% increase in the number of MUs delivered and a 10-40 second decrease in the beam-on time for each 100 MU/min of dose rate increase. The increase in the number of MUs resulted in a reduction of the "beam-on time saved". The exact magnitude of the changes depended on treatment site and planning target volume. These changes can lead to minor, but not negligible, concerns with respect to radiation protection and treatment planning. Although the number of MUs increased more rapidly for more complex treatment plans, the absolute beam-on time savings was greater for these plans because of the higher total number of MUs required to deliver them. We estimate that increasing the IMRT dose rate from 300 to 600 MU/min has the potential to add up to two treatment slots per day for each IMRT linear accelerator. These results will be of value to anyone considering general changes to IMRT dose rates within their clinic.

Poster - Thur Eve - 11: A realistic respiratory trace generator and its application to respiratory management techniques.

Respiratory motion complicates radiotherapy treatment of thoracic and abdominal tumours. Simplified respiratory motions such as sinusoidal and single patient traces are often used to determine the impact of motion on respiratory management techniques in radiotherapy. Such simplifications only accurately model a small portion of patients, as most patients exhibit variability and irregularity beyond these models. We have preformed a comprehensive analysis of respiratory motion and developed a software tool that allows for explicit inclusion of variability. We utilize our realistic respiratory generator to customize respiratory traces to test the robustness of the estimate of internal gross target volumes (IGTV) by 4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT for regular breathing motion. When amplitude variability was introduced the accuracy of the estimate slightly, but the absolute differences were still < 3 mm for both modalities. Poor agreement was shown with the addition of baseline drifts. Both modalities were found to underestimate the IGTV by as much as 30% for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate accuracy. The respiratory trace generator was advantageous for examining the difference between 4DCT and CBCT IGTV estimation under variable motions. It provided useful implementation abilities to test specific attributes of respiratory motion and detected issues that were not seen with the regular motion studies. This is just one example of how the respiratory trace generator can be utilized to test applications of respiratory management techniques.

Poster - Thur Eve - 55: Monte Carlo simulations of variations in planned dose distributions in a prostate patient population.

Clinical outcome studies with clear and objective endpoints are necessary to make informed radiotherapy treatment decisions. Commonly, clinical outcomes are established after lengthy and costly clinical trials are performed and the data are analyzed and published. One the challenges with obtaining meaningful data from clinical trials is that by the time the information gets to the medical profession the results may be less clinically relevant than when the trial began, An alternative approach is to estimate clinical outcomes through patient population modeling. We are developing a mathematical tool that uses Monte Carlo techniques to simulate variations in planned and delivered dose distributions of prostate patients receiving radiotherapy. Ultimately, our simulation will calculate a distribution of Tumor Control Probabilities (TCPs) for a population of patients treated under a given protocol. Such distributions can serve as a metric for comparing different treatment modalities, planning and setup approaches, and machine parameter settings or tolerances with respect to outcomes on broad patient populations. It may also help researchers understand differences one might expect to find before actually doing the clinical trial. As a first step and for the focus of this abstract we wanted to see if we could answer the question: "Can a population of dose distributions of prostate patients be accurately modeled by a set of randomly generated Gaussian functions?" Our results have demonstrated that using a set of randomly generated Gaussian functions can simulate a distribution of prostate patients.

Using cone-beam CT projection images to estimate the average and complete trajectory of a fiducial marker moving with respiration.

Stereotactic body radiotherapy of lung cancer often makes use of a static cone-beam CT (CBCT) image to localize a tumor that moves during the respiratory cycle. In this work, we developed an algorithm to estimate the average and complete trajectory of an implanted fiducial marker from the raw CBCT projection data. After labeling the CBCT projection images based on the breathing phase of the fiducial marker, the average trajectory was determined by backprojecting the fiducial position from images of similar phase. To approximate the complete trajectory, a 3D fiducial position is estimated from its position in each CBCT project image as the point on the source-image ray closest to the average position at the same phase. The algorithm was tested with computer simulations as well as phantom experiments using a gold seed implanted in a programmable phantom capable of variable motion. Simulation testing was done on 120 realistic breathing patterns, half of which contained hysteresis. The average trajectory was reconstructed with an average root mean square (rms) error of less than 0.1 mm in all three directions, and a maximum error of 0.5 mm. The complete trajectory reconstruction had a mean rms error of less than 0.2 mm, with a maximum error of 4.07 mm. The phantom study was conducted using five different respiratory patterns with the amplitudes of 1.3 and 2.6 cm programmed into the motion phantom. These complete trajectories were reconstructed with an average rms error of 0.4 mm. There is motion information present in the raw CBCT dataset that can be exploited with the use of an implanted fiducial marker to sub-millimeter accuracy. This algorithm could ultimately supply the internal motion of a lung tumor at the treatment unit from the same dataset currently used for patient setup.

A pragmatic protocol for I-131 rhTSH-stimulated ablation therapy in patients with renal failure.

PURPOSE: Ablation of thyroid remnants in patients with differentiated thyroid carcinoma and renal failure can be challenging because of the altered and variable clearance rates of iodine from the blood secondary to variations in dialysis protocols, which complicate the selection of the appropriate I-131 dose. The advent of recombinant human TSH allows a simpler approach to dosimetry and ablation without rendering the patient hypothyroid. Avoidance of hypothyroidism may be an important consideration for patients who are experiencing various morbidities from conditions associated with renal failure. METHOD: Three patients on dialysis, who had undergone total thyroidectomy and were euthyroid on L-thyroxine replacement, were given diagnostic doses of I-131 followed by blood and whole-body retention measurements through serial dialyses to determine individual blood clearance rates. After administration of rhTSH, each patient received an ablative dose of I-131 calculated to keep total body dose below 1 Gy. RESULTS: The treatments were administered without complications, and in follow-up imaging of 2 available patients, the ablations were demonstrated to be complete. CONCLUSION: Dosimetry performed on euthyroid dialysis patients permits I-131 dose selection and avoids the additional morbidity of hypothyroidism.

5-HT(3) receptors, alcohol and aggressive behavior in mice.

Alcohol is a positive modulator at the 5-HT(3) receptor, which has been implicated in alcohol drinking, anxiety and aggression. The reported experiments explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol-heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of alcohol, after which they confronted an intruder. Half of the CFW mice exhibited consistently increased aggressive behavior after alcohol and were designated as showing alcohol-heightened aggression, the others showed no increase and were designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist, ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of CFW mice without affecting non-aggressive behaviors. Zacopride also reduced aggression effectively in both groups of mice, but at high doses began to affect walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type mice (WT) were tested for aggressive behavior in their home cage. In those individuals that fought in tests of resident-intruder aggression, no differences were found in aggression after alcohol intake. In tests of aggression without alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of 56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive effects, although these effects depend on the genetic background of the mice.

Ovarian follicular growth and atresia: the relationship between cell proliferation and survival.

Growth factors and steroids play an important role in the regulation of ovarian follicular development. In cattle, two of the earliest detectable differences between the healthy dominant follicle selected for development to the ovulatory stage and subordinate follicles destined to undergo atresia are the greater availability of IGF and the greater capacity to produce estradiol in the dominant follicle. We have shown that IGF-I and estradiol stimulate the proliferation of bovine granulosa cells in vitro and promote granulosa cell survival by increasing resistance to apoptosis. Furthermore, the ability of IGF-I and estradiol to increase resistance to apoptosis is tied to their ability to promote progression through the cell cycle. Blocking the cell cycle at the transition between the first gap phase and the DNA synthesis phase using a specific inhibitor prevented the protective effects of IGF-I and estradiol against apoptosis. Further experiments showed that the protective effect of IGF-I against apoptosis is mediated by the stimulation of phosphatidylinositol 3-kinase and its downstream target, protein kinase B/Akt. Constitutive activation of Akt by the infection of granulosa cells with a recombinant Akt adenovirus protected against apoptosis, and this effect also depended on cell cycle progression. These experiments show that the protective effect of estradiol and IGF-I against apoptosis depends on unperturbed progression through the cell cycle. Once follicles have developed to the preovulatory stage, the LH surge induces terminal differentiation of granulosa cells and withdrawal from the cell cycle. Bovine granulosa cells withdraw from the cell cycle by 12 h after the LH surge and become resistant to apoptosis, even in the absence of growth factors. Treatment with a progesterone receptor antagonist in vitro caused reentry of granulosa cells into the cell cycle and susceptibility to apoptosis, suggesting that induction of progesterone receptor expression by the LH surge is required for cell cycle withdrawal and resistance to apoptosis. In summary, the susceptibility of granulosa cells to apoptosis depends on the cell cycle. Proliferating granulosa cells in growing follicles depend on growth factors for survival, whereas cells that have terminally differentiated in response to the LH surge are resistant to apoptosis and relatively independent of growth factors for survival.

Susceptibility of ovarian granulosa cells to apoptosis differs in cells isolated before or after the preovulatory LH surge.

The luteinizing hormone (LH) surge initiates the final stages of ovarian follicle development, and induces ovulation and luteinization of preovulatory follicles. To investigate whether exposure to the LH surge alters follicle cell susceptibility to apoptosis, granulosa and theca cells were isolated from bovine preovulatory follicles before and 14 h after injection of GnRH to induce an LH surge. Granulosa cells isolated before the LH surge were susceptible to apoptosis induced by soluble Fas ligand or serum withdrawal, while cells isolated after the LH surge were resistant to apoptosis. Resistance to Fas-mediated apoptosis was not associated with decreased Fas mRNA or protein levels. Pretreatment of granulosa cells isolated after the LH surge with the protein synthesis inhibitor cycloheximide rendered the cells susceptible to Fas-mediated apoptosis, indicating that inhibition of apoptosis was mediated by expression of labile survival factors. Theca cells were sensitive to Fas-mediated apoptosis before and after exposure to the LH surge. Resistance to apoptosis of granulosa cells from preovulatory follicles after the LH surge may be important for normal ovulation and luteinization.

Control of vancomycin-resistant enterococcus in health care facilities in a region.

BACKGROUND: In late 1996, vancomycin-resistant enterococci were first detected in the Siouxland region of Iowa, Nebraska, and South Dakota. A task force was created, and in 1997 the assistance of the Centers for Disease Control and Prevention was sought in assessing the prevalence of vancomycin-resistant enterococci in the region's facilities and implementing recommendations for screening, infection control, and education at all 32 health care facilities in the region. METHODS: The infection-control intervention was evaluated in October 1998 and October 1999. We performed point-prevalence surveys, conducted a case-control study of gastrointestinal colonization with vancomycin-resistant enterococci, and compared infection-control practices and screening policies for vancomycin-resistant enterococci at the acute care and long-term care facilities in the Siouxland region. RESULTS: Perianal-swab samples were obtained from 1954 of 2196 eligible patients (89 percent) in 1998 and 1820 of 2049 eligible patients (89 percent) in 1999. The overall prevalence of vancomycin-resistant enterococci at 30 facilities that participated in all three years of the study decreased from 2.2 percent in 1997 to 1.4 percent in 1998 and to 0.5 percent in 1999 (P<0.001 by chi-square test for trend). The number of facilities that had had at least one patient with vancomycin-resistant enterococci declined from 15 in 1997 to 10 in 1998 to only 5 in 1999. At both acute care and long-term care facilities, the risk factors for colonization with vancomycin-resistant enterococci were prior hospitalization and treatment with antimicrobial agents. Most of the long-term care facilities screened for vancomycin-resistant enterococci (26 of 28 in 1998 [93 percent] and 23 of 25 in 1999 [92 percent]) and had infection-control policies to prevent the transmission of vancomycin-resistant enterococci (22 of 25 [88 percent] in 1999). All four acute care facilities had screening and infection-control policies for vancomycin-resistant enterococci in 1998 and 1999. CONCLUSIONS: An active infection-control intervention, which includes the obtaining of surveillance cultures and the isolation of infected patients, can reduce or eliminate the transmission of vancomycin-resistant enterococci in the health care facilities of a region.

Relationship of Fas ligand expression and atresia during bovine follicle development.

The Fas antigen (Fas) is a cell surface receptor that may be involved in the initiation and progression of follicle cell apoptosis during atresia. Fas initiates apoptosis in sensitive cells after binding Fas ligand (FasL). Other experiments have shown that expression of Fas mRNA and responsiveness to Fas-mediated apoptosis vary in bovine granulosa and theca cells during follicle development. In the present study, FasL mRNA content was measured and Fas and FasL protein expression was examined in bovine granulosa and theca cells of healthy dominant follicles and the two largest atretic subordinate follicles on day 5 of the oestrous cycle (day 0 = oestrus), and of dominant follicles from the first wave of follicle development after they had become atretic and showed no growth for 4 days. FasL mRNA content was higher in granulosa cells from atretic compared with healthy follicles. FasL mRNA content was also higher in theca cells from atretic subordinate compared with healthy dominant follicles on day 5, but did not differ between theca cells from healthy and atretic dominant follicles. Immunohistochemical staining for FasL was more intense in theca compared with granulosa cells and in atretic compared with healthy follicles. Immunohistochemical staining for Fas was more intense in granulosa compared with theca cells and in atretic subordinate compared with healthy dominant follicles on day 5. Immune cells, known to express Fas and FasL, were localized in the theca, but not the granulosa, cell layer of all follicles. Higher concentrations of Fas and FasL in cells from atretic follicles, together with the previous demonstration of increased responsiveness of granulosa cells from subordinate follicles to FasL-induced apoptosis, support a potential role for FasL-mediated apoptosis during ovarian follicle atresia.

Evaluation of a successful vancomycin-resistant Enterococcus prevention intervention in a community of health care facilities.

BACKGROUND: In April 1997, vancomycin-resistant enterococci (VRE) emerged in several health care facilities in the Siouxland region and a VRE Task Force was formed. From 1997 through 1999, an evaluation of VRE prevalence at 30 facilities was performed. METHODS: In 1999, we conducted a survey and focus groups of health care workers to address initial reactions to VRE, feasibility of the Task Force recommendations, and lessons learned. RESULTS: Personnel at 29 (97%) facilities surveyed completed the questionnaire, and 15 health care workers from 11 facilities participated in 5 focus groups. The outcomes of expanded education and improved awareness of VRE for patients and health care workers were ranked the No. 1 priority overall and by long-term care facility personnel. Respondents agreed that Task Force recommendation adherence had significantly improved infection control (83%) and that the Task Force was an appropriate mechanism to coordinate infection control efforts (90%). Focus groups commented that it was most difficult to educate family members about VRE; they expressed concern about variation between VRE policies, especially between acute care and long-term care facilities, and about the quality of life of isolated patients. CONCLUSIONS: Our data illustrate that this intervention has been far-reaching and include the development of a health care infrastructure that may be used as a model to address additional health care issues (eg, emerging pathogens or biological threats).

Apoptosis of bovine granulosa cells after serum withdrawal is mediated by Fas antigen (CD95) and Fas ligand.

Ovarian follicular atresia occurs by apoptosis of granulosa and theca cells. The Fas antigen (Fas), a cell surface receptor that triggers apoptosis when activated by Fas ligand (FasL), may be involved in this process. A possible role of the Fas pathway in mediating serum withdrawal-induced apoptosis of granulosa cells was examined. Granulosa cells collected from 5- to 10-mm bovine follicles were cultured in DMEM-F12 containing serum for 3 days, deprived of serum, and live cells were counted at various times after serum withdrawal. Cell death increased significantly 6 h after serum withdrawal (21% +/- 7%; P: < 0.05 vs. 0 h) and continued to increase until 24 h (43% +/- 6%). No further increases in cell death were observed through 72 h. Detection of the translocation of phosphatidylserine to the outer surface of the cell membrane by annexin V binding indicated that cells died by apoptosis. Quantitative reverse transcriptase-polymerase chain reaction assays showed no changes in Fas mRNA levels but a 4.7-fold increase in FasL mRNA 3 h after serum withdrawal (P: < 0.05 vs. 0 h). FasL mRNA remained elevated through 24 h and returned to basal levels at 48 h. Immunohistochemical staining showed that both Fas and FasL protein increased on the cell surface within 3 h and remained elevated through 12 h (the last time point tested). Binding of FasL to Fas was blocked with two reagents that bind to the extracellular domain of FasL: an anti-FasL antibody and Fas:Fc, a chimeric protein consisting of the Fc portion of human immunoglobulin G and the extracellular domain of human Fas. Cell death 24 h after serum withdrawal was reduced 55% +/- 10% and 34% +/- 12% by anti-FasL antibody and Fas:Fc, respectively (P: < 0.05 vs. no blocking protein). In conclusion, serum withdrawal-induced apoptosis of bovine granulosa cells is mediated at least partially by Fas/FasL interactions. These results are consistent with a potential role of Fas in an autocrine or paracrine pathway to trigger ovarian follicular atresia.