Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database

BACKGROUND: Because of public awareness and screening, the incidence of clinically localized prostate cancer has increased dramatically in the last 15 years. The Department of Defense Center for Prostate Disease Research (CPDR) was established by the US Congress in 1991 to study prostate cancer in the US military health care system. A key component of CPDR is a multicenter prospective and retrospective prostate research database that collects comprehensive standardized data on all consenting patients. To verify and document changes in the epidemiology of men electing radical prostatectomy (RP) as primary treatment for their localized prostate cancer, we undertook an analysis of such cases when the PSA screening test became widely available and used. METHODS: The CPDR database consists of standardized data collection forms for each episode of care completed prospectively, and in some cases, retrospectively, on men with prostate cancer and those undergoing a prostate biopsy for presumed cancer at participating medical centers. In July 2001, a query of all RPs performed between January 1, 1991, and December 31, 2000, was conducted, revealing 3681 cases for analysis from 9 hospital sites. These cases were analyzed over time (calendar year), and changes in the characteristics of the patients, disease severity, and surgical results were compared. RESULTS: There was a significant shift to younger men undergoing RP with the median age declining to 62.3 years old by 2000, and more than 40% of the men were less than 60 years old. There was an increase in African-Americans undergoing RP and a large increase in clinical stage T1 disease candidates of both races representing 56.5% of men by 2000. There was a large increase in patients having pretreatment PSA levels between 4 and 10 ng/mL (59.2% by 2000). Retropubic approach was predominant (over 80%) and was associated with a much lower blood loss by 2000 (approximately 800 mL). There was an increase in use of nerve-sparing procedures, and operative time declined significantly to a median of 3.5 hours by 2000. Finally, there was a marked surgical stage migration with a higher proportion of men with organ-confined disease and negative surgical margins; by 2000, 63.4% had pT2 disease. The early outcomes improved with a 1-year disease-free survival in excess of 93%. CONCLUSIONS: RP is being performed more commonly on younger men with earlier stage disease in the PSA era. The operation is now performed more rapidly with less blood loss, and the surgical pathology outcome end points and early disease-free survival are improved. These results portend well for improved long-term outcomes of surgical therapy.     

A comparison of household lead exposure assessment methods in an old,urban community

The accurate assessment of lead hazards within the household is critical to the prevention of lead exposure to children living in urban communities. Although dust wipes are currently accepted as the best method of assessing lead hazards, questionnaires and visual inspections are also used. This study evaluates the level of agreement among these three methods of assessment using a sample of 126 women living in old, urban houses. The level of agreement was assessed using the kappa statistic, which adjusts for chance agreement. Overall, the kappa results for both the participant's assessment (questionnaire) and the visual inspector's assessment were low, indicating only slight to moderate agreement with the dust lead wipe levels. Kappas were higher and more consistent for the visual inspector's assessment than for the participant's assessment. These results indicate that visual inspections and participant questionnaires may provide less accurate information regarding lead hazards within the household than dust wipes. Because lead hazard recognition is important in the prevention of lead exposure in children, our data suggest that emphasis should be placed on the measurement of dust lead levels directly in assessing household lead hazards, possibly by teaching women in high-risk neighborhoods to take dust samples themselves.     

The effect of guided imagery and amitriptyline on daily fibromyalgia pain: a prospective, randomized, controlled trial

OBJECTIVE: The effectiveness of an attention distracting and an attention focusing guided imagery as well as the effect of amitriptyline on fibromyalgic pain was studied prospectively. METHODS: Fifty-five women with previously diagnosed fibromyalgia were monitored for daily pain (VAS) in a randomized, controlled clinical trial. One group received relaxation training and guided instruction in "pleasant imagery" (PI) in order to distract from the pain experience (n=17). Another group received relaxation training and attention imagery upon the "active workings of the internal pain control systems", "attention imagery" (AI) (n=21). The control group (CG) received treatment as usual (n=17). Patients were also randomly assigned to 50-mg amitriptyline/day or placebo. Some psychological and socio-demographic variables were also measured initially. The slopes of diary pain ratings over a 4-week period were used as the outcome measures. RESULTS: We found significant differences of the pain-slopes between the three psychological conditions (P=0.0001). The pleasant imagery (P<0.005), but not the attention imagery group's slope, declined significantly when compared with the control group (P>0.05). There was neither a difference between the amitriptyline and placebo slopes (main effects, P=0.98) nor a significant amitriptyline x psychological interaction (P=0.76). CONCLUSION: Pleasant imagery (PI) was an effective intervention in reducing fibromyalgic pain during the 28-day study period. Amitriptyline had no significant advantage over placebo during the study period.     

Parkinson's disease, CYP2D6 polymorphism, and age

OBJECTIVE: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. METHODS: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. RESULTS: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset PD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 at mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. CONCLUSION: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect.     

Dopamine precursors and brain function in phenylalanine hydroxylase deficiency

Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. In experimental studies it has been shown that the synthesis and release of dopamine can be influenced by an increase in the availability of tyrosine. In PHD an extra dietary intake of three doses of tyrosine (160mg/kg/24h) induced a shortsning of reaction time and decreased variability, and in a double-blind crossover study a similar dose has been reported to induce an improvement on psychological tests. In a study with lower doses of tyrosine (110mg/kg/24h) no effect was found on reaction time tests. These findings need to be substantiated, and more detailed information should be obtained.