Artificial urinary sphincter insertion in renal transplant recipients

The prosthetic urinary sphincter has contributed significantly to the improved management of urinary incontinence during the past 25 years. However, the safety of these devices in immunosuppressed patients is not well reported. We describe the successful insertion of the AMS 800 artificial urinary sphincter in two renal transplant recipients.     

Time of day effects on sympathoadrenal and pressor reactivity to exercise in healthy men

Summary To investigate the influence of time of day on sympathoadrenal and pressor reactivity during exercise, eight trained men [age, mean (SD), 24 (0.5) years; maximal oxygen uptake ( ), 4.7 l·min^–1] performed bouts of static (ST) and dynamic (DYN) exercise at 0600–0800 hours (AM) and at 1600–1800 hours (PM). The ST protocol utilized a two-leg isometric contraction at 30% maximum voluntary contraction until failure, and was monitored by a strain gauge interfaced from a leg extension apparatus to a computer. Heart rate (f_c) and blood pressure ( ) responses were recorded at rest, after 1 and 2 min of exercise, and at failure. Epinephrine (EPI) and norepinephrine (NE) levels were recorded before exercise, and after 2 min of exercise. The DYN exercise protocol involved stationary. cycling for consecutive 6-min periods at 60% and 80% . f_c, , EPI, and NE were recorded before exercise and at each workload. No differences were observed in preexercise or exercise f_c under any condition. Preexercise did not differ under any condition. The response to DYN was significantly higher at 80% during PM only. was significantly higher in ST-PM at 1 min, 2 min, and failure. Elevations in both systolic and diastolic P _a contributed to this difference. Preexercise EPI-ST-AM was significantly elevated vs PM, but no other preexercise data were significantly different. Absolute exercise levels were significantly higher for EPIST-PM vs AM only, but the percentage change from baseline was significantly (P<0.01) higher in ST-PM for EPI (+231% PM vs + 32% AM) and NE (+352% PM vs +216% AM). The EPI and NE responses to DYN exercise tended to be higher in AM, but were not significantly different. These data support a time of day pattern in sympathoadrenal and pressor reactivity to exercise that is dependent on the type of activity involved but independent of baseline patterns.     

An inhibitor of glycinamide ribonucleotide formyltransferase is selectively cytotoxic to cells that lack a functional G1 checkpoint

Purpose: We studied the effects of purine depletion on the cell cycle using a specific inhibitor of de novo purine biosynthesis, AG2034, an inhibitor of glycinamide ribonucleotide formyltransferase (GARFT). Methods: Cytotoxicity was determined by clonogenic assays, and cell cycle perturbations by flow cytometry. Ribonucleotide pools were measured by anion exchange high-pressure liquid chromatography, and DNA strand-breaks were determined by alkaline elution and by the TUNEL assay. Results: When cells were maintained in standard tissue culture medium, which contained 2.2 μM folic acid, AG2034 was cytostatic in all the cell lines tested. Under low-folate conditions (50 nM folic acid), AG2034 caused up to 50% cell death in cell lines that possessed a functional G1 checkpoint (A549, MCF-7), but was only cytostatic to the remaining cells, even at very high concentrations (100 μM ). In contrast, AG2034 at 10 nM or 100 nM killed all the cells in cultures of HeLa/S3 or SW480 cells, which lack a functional G1 checkpoint. Flow cytometry studies indicated that in G1 checkpoint-competent cells, AG2034 caused a G1 arrest. Those cells (up to 50%) that were already in S phase died, but the cells that were in G1 arrest maintained viability, based upon clonogenic assays, for many days. In G1 checkpoint-deficient cells, no G1 arrest was seen after AG2034 treatment, all cells progressed into S phase, and all cells died. Measurement of DNA strand-breaks, either by alkaline elution or by the dUTP end-labelling technique, indicated no DNA strand-breaks 24 h after AG2034 treatment, indicating that purine nucleotide depletion can trigger the G1 checkpoint in the absence of DNA damage. Conclusion: Purine depletion causes slow cell death in cells that have passed the G1 checkpoint, but cytostasis in cells that are arrested at the G1 checkpoint. The GARFT inhibitor, at physiological folate concentrations, thus causes selective cytotoxicity to cells lacking a functional G1 checkpoint. Received: 8 May 1997 / Accepted: 26 June 1997     

Methadone maintenance in general practice: impact on staff attitudes

Background  

The evaluation of a structured protocol for the discharge of stabilised patients on methadone maintenance to general practice provided an opportunity to evaluate the impact on the attitudes of general practitioners (GPs) and practice staff.     

Chronic Hepatitis C Infection in a Rural Medicaid HMO

CONTEXT: Chronic hepatitis C infection (CHCI) is an increasingly common problem, affecting about 2% of the US population. The cost and complexity of treatment and difficulties in communicating with the infected population are of concern to insurers and health planners. PURPOSE: To describe the clinical features of patients with CHCI in a rural Medicaid-covered population and to describe a method developed for treating CHCI in an underserved rural community. METHODS: We developed a disease management approach to patients with CHCI receiving insurance coverage through a Medicaid HMO in rural Oregon. A locally based multidisciplinary hepatitis committee was formed to develop a management protocol and a process for selecting patients for treatment. The committee met monthly to develop the treatment plan for individual patients. Day-to-day treatment was provided by a nurse under the supervision of the committee. FINDINGS: One hundred forty-three adults with CHCI were identified by their primary care physicians. About half the patients had a type 1 genotype. Treatment with pegylated interferon and ribavirin was completed on 21 persons, 11 (52%) of whom had a virologic cure. Problems with treatment toxicity were common. Patient satisfaction with the treatment by the nurse was high. CONCLUSIONS: CHCI is common in this rural, nonminority Medicaid-insured population. A locally based disease management model was developed that was well received by patients and was successful in delivering a high quality of care for people with CHCI in a rural area.     

Re-embedding trust: unravelling the construction of modern diets

Recent controversies surrounding the food industry and its contribution to diet-related illnesses provide fertile ground for re-examining where power lies in food systems. A review of the literature reveals a wide range of powerful actors, contradictory assessments about consumer power and numerous examples of producers and medical authorities expending significant effort to shape the criteria by which consumers exercise choice. Expertise from the fields of marketing, advertising, psychology and nutrition science has been marshalled for close to a century to create commodity contexts that are sympathetic to mass-produced foods. In the last quarter of the twentieth century, however, a new dynamic entered the equation: the battle between technical rationality and reflexive consumers. Consumers are questioning the credentials of foods and those who promote them and, simultaneously, are seeking hope and help from the food system. As a result, health claims have become a most important ingredient in the fight for competitive advantage. This paper describes how the re-embedding of trust in a food supply dominated by corporations is being attempted through the nutritionalization of the food supply. On the basis of two studies, the authors identify the actors, processes, ideological basis and points of resistance that comprise what they are terming an emergent ‘diets-making complex’ (DMC). By intensifying the influence of science and nutritional claims in dietary discourse, the DMC has the potential to circumscribe policy options about food and health, because appeals to individual health are obscuring a social view of the food supply.     

Approach to sleep disorders in the nursing home setting. REVIEW ARTICLE

Evidence suggests that sleep disorders and sleep fragmentation are very common in nursing home residents. A variety of factors contribute to these sleeping difficulties, including age-related changes in sleep; the high prevalence of dementia, depression, medical illness and medications that affect sleep; and sleep disorders such as respiratory disturbance of sleep. Other important factors include common lifestyle characteristics in nursing home residents (such as inactivity, large amounts of time spent in bed, lack of bright light exposure, and poor sleep hygiene) and the disruptive night-time nursing home environment. Recent interventional studies suggest that improvement in the nursing home environment may be an important aspect of the management of sleeping difficulties. Assessment and management of sleeping problems in nursing home residents should involve comprehensive assessment and treatment of the multiple factors that can interfere with sleep. Residents who fail these interventions can be considered for treatment with sleeping medications. Unfortunately, there is little data on the effectiveness of sleeping medications and the specific management of sleep disorders in this setting. Future research should focus on clarifying the contribution of various environmental factors to sleep impairment, and the testing of these various interventions on sleep.     

Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer.

PURPOSE: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome. RESULTS: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung. CONCLUSIONS: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.