Dysuria after permanent prostate brachytherapy

PURPOSE: Although numerous prostate cancer quality-of-life studies have been reported, a paucity of data exists regarding brachytherapy-related dysuria. In this study, we evaluated the incidence and temporal resolution of dysuria, along with the influence of multiple treatment, clinical, and dosimetric parameters. MATERIALS AND METHODS: Five hundred eighty-one consecutive patients without a preimplant history of transurethral resection of the prostate underwent brachytherapy between January 1998 and December 2001 for clinical T1c-T3a (1997 AJCC) adenocarcinoma of the prostate gland. The evaluated population consisted of the 546 patients who had completed at least two postimplant dysuria evaluations. The median patient follow-up was 26.4 months. In all patients, alpha-blocker therapy was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline. The frequency of dysuria was assessed on a 1-5 scale using the IPSS scoring criteria. The dysuria severity was scored on a 1-10 scale. The clinical parameters evaluated included age, T stage, preimplant IPSS, ultrasound volume, and elapsed time since implantation. The treatment parameters included the use of neoadjuvant hormonal manipulation, use of supplemental external beam radiotherapy, isotope, and total implanted seed strength. The dosimetric parameters included values of the minimal dose received by 90% of the prostate, the percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and the median and maximal urethral doses. RESULTS: The incidence of dysuria peaked at 52% 1 month after implantation. The median dysuria frequency score was 0 of 5 for all patients and 2 of 5 for those reporting dysuria. The median severity score was 0 of 10 for the entire cohort and 3 of 10 for those reporting dysuria. For the entire group, both the frequency and the severity of dysuria steadily improved with time, with near complete resolution of dysuria at 45 months. For those patients reporting dysuria, neither the frequency nor the severity revealed any durable improvement for approximately 36 months. Patients with dysuria displayed higher postimplant IPSSs. Of the 7 IPSS questions, nocturia and incomplete voiding were the best surrogates for dysuria. The isotope, supplemental external beam radiotherapy, hormonal status, minimal dose received by 90% of the prostate, and urethral dose did not predict for dysuria. CONCLUSIONS: After permanent prostate brachytherapy, dysuria is a relatively common event, but only rarely severe in frequency or intensity. At approximately 45 months after brachytherapy, dysuria appears to resolve in almost all patients.     

MLL-mediated transcriptional gene regulation investigated by gene expression profiling

The human mixed lineage leukemia (MLL) gene is involved in about 50 different chromosomal translocations, associated with the disease phenotype of acute leukemia. However, the normal function of MLL is less understood. Homozygous knockouts of murine Mll were embryonal lethal, while heterozygous disruption led to aberrant hox gene expression associated with skeletal malformations, growth retardation, and impaired hematopoiesis. To understand MLL functions on the molecular level, gene expression profiling experiments were performed with a pair of murine cell lines (MLL(+/+) and MLL(-/-)). Microarray hybridization experiments revealed 197 potential target genes that are differentially expressed, providing new and important clues about MLL functions.     

Multiple myeloma and diesel and other occupational exposures in swedish construction workers

We examined the relationships between occupational exposures and the risk of multiple myeloma among male construction workers in Sweden. A total of 446 myeloma subjects were identified among 365,424 male workers followed from 1971 to 1999. Occupational exposure was assessed using a semiquantitative job-exposure matrix, based on a survey carried out by the Construction Industry's Organization for Working Environment, Occupational Safety and Health in Sweden. Rate ratios (RRs) in the exposed groups relative to the unexposed groups were estimated by Poisson regression. We found an increased risk (RR = 1.3, 95% CI 1.04-1.71) among construction workers exposed to diesel exhaust. Adjustment for other occupational exposures did not change this estimate (RR = 1.3, 95% CI 1.00-1.77). However, there was no monotonic increase in risk with estimated level of exposure (RR for low = 1.4, moderate = 1.1, high = 1.4). There was no evidence of increased risk associated with the other occupational exposures among these construction workers, including asbestos, asphalt, cement dust, metal dust, mineral wool, organic solvents, stone dust and wood dust. Occupational exposure to diesel exhaust in the Swedish construction industry may present a small risk of multiple myeloma, but lack of an exposure-response trend tempers our ability to draw clear conclusions.     

The nurse, M.D. and IT. Executive dialogue series

Clinical information systems are proven to enhance workflow and outcomes, and yet hospitals often face staff resistance when systems are installed. This roundtable discussion explores how nurses and physicians can collaborate on developing IT systems.     

Implementing psychiatric advance directives: Service provider issues and answers

Psychiatric advance directives (PADs) are an emerging method for adults with serious and persistent mental illness to document treatment preferences in advance of periods of incapacity. This article presents and responds to issues most frequently raised by service providers when planning for implementation of PADs. Issues discussed include access to PADs; competency to execute PADs; the relationship of PADs to standards of care, resource availability, and involuntary treatment; roles of service providers and others in execution of PADs; timeliness and redundancy of PAD information; consumer expectations of PADs; complexity of PADs; revocation and activation; legal enforceability of PADs; the role and powers of agents; liability for honoring and not honoring PADs; and use of PADs to consent for release of health care information. Recommendations are made for training staff and consumers, consideration of statute development, and methods to reduce logistical, attitudinal, and system barriers to effective use of PADs.     

Redecoration of apartments promotes obstructive bronchitis in atopy risk infants--results of the LARS Study

Findings by other authors indicate that exposure to chemical emissions from indoor paint is related to asthma symptoms in adults. In their first years of life children are receptive to obstructive airway diseases. The aim of this study was to investigate the influence of redecoration of the apartment on airway symptoms in infants during the first two years of life. The Leipzig Allergy Risk Children Study (LARS) is a birth cohort study with the following inclusion criteria: double positive family atopy anamnesis, cord blood IgE > 0.9 kU/l, or low birth weight between 1500-2500 g. Within the context of LARS, 186 parents of risk children completed a questionnaire on the respiratory symptoms of their children and the redecoration of their apartment at the end of the first and second year of life. A total 22% of the children suffered from obstructive bronchitis once or more during their first year, and 11% experienced this condition during their second year of life. Redecoration of the apartment had a significant influence on the appearance of obstructive bronchitis in the first (OR 4.1 95% CI 1.4-11.9) and in the second year of life (OR 4.2 95% CI 1.4-12.9). (The OR are adjusted for cord blood-IgE > 0.9 kU/l, birth weight < or = 2500 g, male sex and double positive parental atopy anamnesis, dampness, smoking or pet in the apartment). Simultaneous contamination from redecoration activities and additional exposures such as smoking, a pet or dampness in the apartment increased the risk for obstructive bronchitis in the first year (OR 9.1; 95% CI 2.3-34.8) as well as in the second year (OR 5.1; 95% CI 1.6-15.6). Our data suggest that redecoration of the apartment is associated with the development of acute inflammations, but not with a chronic influence on the airways in atopy risk infants. At an exposure to more than one environmental factor, pronounced effects were seen.     

Role of tumor necrosis factor receptor 1 (p55) in hepatocyte proliferation during acetaminophen-induced toxicity in mice

Hepatocyte proliferation represents an important part of tissue repair. In these studies, TNF receptor 1 (TNFR1) knockout mice were used to analyze the role of TNF-alpha in hepatocyte proliferation during acetaminophen-induced hepatotoxicity. Treatment of wild-type (WT) mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis. This was associated with proliferation of hepatocytes surrounding the damaged areas, which was evident at 24 h. The cell cycle regulatory proteins, cyclin D1 and cyclin A, were also up regulated in hepatocytes. In contrast, in TNFR1-/- mice, which exhibit exaggerated acetaminophen hepatotoxicity, hepatocyte proliferation, and expression of cyclin D1 and cyclin A, as well as the cyclin dependent kinases, Cdk4 and Cdk2, were reduced. The cyclin-dependent kinase inhibitor p21 was also induced in the liver following acetaminophen administration. This was greater in TNFR1-/- mice compared to WT mice. To investigate mechanisms mediating the reduced hepatic proliferative response of TNFR1-/- mice, we analyzed phosphatidyl inositol-3-kinase (PI-3K) signaling. In both WT and TNFR1-/- mice, acetaminophen caused a rapid increase in total PI-3K within 3 h. Acetaminophen also increased phosphorylated PI-3K, but this was delayed 6-12 h in TNFR1-/- mice. Expression of Akt, a downstream target of PI-3K, was increased in both WT and TNFR1-/- mice in response to acetaminophen. However, the increase was greater in WT mice. Acetaminophen-induced expression of phosphorylated STAT3, a key regulator of cytokine-induced hepatocyte proliferation, was also delayed in TNFR1-/- mice relative to WT. These data suggest that TNF-alpha signaling through TNFR1 is important in regulating hepatocyte proliferation following acetaminophen-induced tissue injury. Delayed cytokine signaling may account for reduced hepatocyte proliferation and contribute to exaggerated acetaminophen-induced hepatotoxicity in TNFR1-/- mice.