Biomedical subjects

R L Dunn

Publications and source records attributed to R L Dunn.

At least 19 recordsLinked to original sources

PubMed2005

Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease.

OBJECTIVES: To enumerate the amount of circulating tumor cells (CTCs) in patients with advanced prostate cancer and to investigate the relationship between these numbers, prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) expression, and clinical parameters. METHODS: Whole blood was collected in proprietary CellSave tubes. Mononuclear cell fractions were isolated using epithelial cell antibody-coated magnetic nanoparticles. On one half of each immunomagnetically enriched cell fraction, automated fluorescent microscopy was used to identify the epithelial tumor cells. From the remainder of each sample, RNA extraction, cDNA synthesis, and polymerase chain reaction amplification of PSA and PSM were performed. RESULTS: Eighty-four patients with advanced prostate cancer submitted 130 samples for analysis. Intact CTCs were identified in 62% of samples; 83.3% of CTC-positive and 0% of CTC-negative samples were reverse transcriptase-polymerase chain reaction positive for PSA and PSM (P = 0.001). A significant positive correlation was found between the CTC number and PSA (r = 0.49), alkaline phosphatase (r = 0.47), and lactate dehydrogenase (r = 0.55) levels, and a significant negative correlation with hemoglobin (r = -0.35). The initial Gleason grade, prior therapy, current therapy, and type of metastasis (bone, soft tissue) did not correlate significantly with the CTC number. CONCLUSIONS: The presence of intact CTCs and the expression of PSA and PSM demonstrated robust agreement. The tumor cell numbers reflected current disease status and correlated significantly with the clinical disease indicators of PSA, hemoglobin, and liver function tests. These findings warrant further investigation of the diagnostic and prognostic value of enumerating intact CTCs.

Adult↗

PubMed2003

An EP2 receptor-selective prostaglandin E2 agonist induces bone healing.

The morbidity and mortality associated with impaired/delayed fracture healing remain high. Our objective was to identify a small nonpeptidyl molecule with the ability to promote fracture healing and prevent malunions. Prostaglandin E2 (PGE2) causes significant increases in bone mass and bone strength when administered systemically or locally to the skeleton. However, due to side effects, PGE2 is an unacceptable therapeutic option for fracture healing. PGE2 mediates its tissue-specific pharmacological activity via four different G protein-coupled receptor subtypes, EP1, -2, -3, and -4. The anabolic action of PGE2 in bone has been linked to an elevated level of cAMP, thereby implicating the EP2 and/or EP4 receptor subtypes in bone formation. We identified an EP2 selective agonist, CP-533,536, which has the ability to heal canine long bone segmental and fracture model defects without the objectionable side effects of PGE2, suggesting that the EP2 receptor subtype is a major contributor to PGE2's local bone anabolic activity. The potent bone anabolic activity of CP-533,536 offers a therapeutic alternative for the treatment of fractures and bone defects in patients.

Animals↗

PubMed2002

Effects of GnRH agonist (leuprolide) on reproduction and behaviour in female wapiti (Cervus elaphus nelsoni).

Fertility control offers a potential alternative to traditional methods for regulating the growth of overabundant wild ungulate populations. However, current technology is limited due to practical treatment application, undesirable side-effects and economic considerations. A promising non-steroidal, non-immunological approach to contraception involves the use of a potent GnRH agonist. Two experiments were conducted to evaluate the effectiveness of a GnRH agonist (leuprolide) for controlling fertility in captive female wapiti and to assess physiological and behavioural side-effects of the treatment. In Expt 1, the optimum dose of agonist treatment was determined by measuring serum LH response of eight female wapiti to four formulations of leuprolide (0, 45, 90 and 180 mg) administered as a subcutaneous (s.c.) bioimplant. In Expt 2, the effects of leuprolide on wapiti pregnancy rates, duration of suppression of serum LH and progesterone secretion, and short-term behavioural and physiological side-effects were evaluated. All concentrations of leuprolide in Expt 1 were equally effective in reducing serum LH to non-detectable values throughout the 130 day trial. In Expt 2, leuprolide administered before the breeding season was 100% effective at preventing pregnancy in treated females. Serum LH and progesterone were reduced to baseline values by day 92 and remained at this concentration for 195-251 days after treatment, and returned to pretreatment concentrations in the following breeding season. Reproductive behaviour rates were similar for treated and untreated wapiti for all behaviour categories for both the breeding and post-breeding seasons. Haematology and blood chemistry parameters of treated and un-treated females were similar, and seasonal intake and body weight dynamics appeared normal. In conclusion, leuprolide is a safe, effective contraceptive agent and can potentially suppress fertility in female wapiti for one breeding season.

Animals↗

PubMed2001

The antimutator phenotype of E. coli mud is only apparent and results from delayed appearance of mutants.

Antimutator strains are strains that have a lower mutation rate than the wild-type strain. We have reexamined the properties of one reported antimutator strain of Escherichia coli, termed mud [Mol. Gen. Genet. 153 (1977) 87]. This strain contains a temperature-sensitive mutation in the purB gene, leading to adenine-dependent growth at higher temperature. When grown at permissive or semi-permissive temperature in the absence of adenine it displays large reductions in the number of both spontaneous and mutagen-induced mutants (e.g. several hundred-fold for valine-resistant mutants). However, our studies show that strains containing the purB allele generate mutations at the same level as the wild-type strain, and that the apparent antimutator effect is the consequence of the delayed appearance of mutants on the selective plates. This delay likely results from the combined stress exerted by the adenine deficiency and the presence of the selective agent (i.e. valine).

Adenylosuccinate Lyase↗

PubMed2001

Psychosocial characteristics of individuals with non-stage IV melanoma.

PURPOSE: Melanoma is the fastest growing solid tumor among men and women and accounts for 79% of skin cancer-related deaths. Research has identified that distress is frequently associated with a diagnosis of cancer and may slow treatment-seeking and recovery, increasing morbidity and even mortality through faster disease course. Given that the 5-year survival rates for individuals with melanoma are determined primarily by the depth and extent of spread, distress that interferes with seeking treatment has the potential to be life-threatening. PATIENTS AND METHODS: The current study was designed to identify levels of distress present in individuals seeking treatment at a large, Midwestern, multidisciplinary melanoma clinic. It also focused on determining the quality of life, level of anxiety, and coping strategies used by individuals with melanoma before treatment. Given that the course of treatment and outcome for patients with stage IV disease is vastly different from that of patients with stages I to III disease, they were excluded from the study. RESULTS: Results indicated that most individuals who are presenting to a melanoma clinic do not report a clinically significant level of distress. However, there is some variability in this, with 29% of patients reporting moderate to high levels of distress. Moreover, analyses suggest that distressed individuals are more likely to use maladaptive coping strategies, such as escape-avoidance coping, and to have poorer quality of life. CONCLUSION: Although most individuals do not present with significant levels of distress, a significant minority are distressed and rely more heavily on coping strategies that do not benefit them. Such individuals would likely benefit most from psychological intervention.

Adaptation, Psychological↗

PubMed2001

Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon.

Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and beta-catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Analysis of a managed psychiatric disability program.

The cost of mental illness to employers has been well documented; however, efforts to effectively reduce the costs of psychiatric disability are adversely affected by the fragmentation of health care services. This report is a case study of a program in which a managed behavioral health care organization managed the psychiatric disability of a telecommunications company. Compared with a non-random cohort of claimants not managed under the pilot, the duration of disability was reduced by 23% (17.1 days). Patient and provider satisfaction with the program was high. This study illustrates the potential for effectively reducing the cost of psychiatric disability and the challenges in coordinating health care.

Adult↗

PubMed2001

Assessment of early continence recovery after radical prostatectomy: patient reported symptoms and impairment.

PURPOSE: Patients considering radical prostatectomy often inquire as to when they can expect to regain urinary continence. However, there is a paucity of patient self-reported data regarding the recovery of continence during the initial 3 months after surgery. Our objectives were to assess urinary continence changes early in the postoperative period and determine which of 2 commonly used definitions of continence more closely relate to patient reported urinary impairment. MATERIALS AND METHODS: A prospective study of 90 men with clinically localized prostate cancer who selected radical prostatectomy as primary therapy was conducted. Repeated measures of urinary continence as defined by 1) total urinary control, 2) the use of 1 or 0 pads daily, and 3) small or no problem with urinary function were obtained with a brief survey preoperatively and postoperatively. RESULTS: At 56 days after removal of urethral catheters, the actuarial rates of urinary continence recovery based on definitions 1 to 3 were 43%, 84% and 82%, respectively. The use of definition 2 for continence resulted in a 1.9 times higher actuarial rate for continence recovery when compared to definition 1 at 56 days (p <0.001). However, strong agreement was observed between definitions 2 and 3 (kappa = 0.69). CONCLUSIONS: Urinary control is recovered in a significant proportion of men who undergo radical prostatectomy during the initial 3 months. Continence rates will vary significantly based on the use of alternative definitions. The clinical practice of asking patients how many pads daily they use may be valid, as it corresponds well to the impairment they have.

Aged↗

PubMed2000

Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer.

OBJECTIVES: Health-related quality of life (HRQOL) is an increasingly important endpoint in prostate cancer care. However, pivotal issues that are not fully assessed in existing HRQOL instruments include irritative urinary symptoms, hormonal symptoms, and multi-item scores quantifying bother between urinary, sexual, bowel, and hormonal domains. We sought to develop a novel instrument to facilitate more comprehensive assessment of prostate cancer-related HRQOL. METHODS: Instrument development was based on advice from an expert panel and prostate cancer patients, which led to expanding the 20-item University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) to the 50-item Expanded Prostate Index Composite (EPIC). Summary and subscale scores were derived by content and factor analyses. Reliability and validity were assessed by test-retest correlation, Cronbach's alpha coefficient, interscale correlation, and EPIC correlation with other validated instruments. RESULTS: Test-retest reliability and internal consistency were high for EPIC urinary, bowel, sexual, and hormonal domain summary scores (each r >/=0.80 and Cronbach's alpha >/=0.82) and for most domain-specific subscales. Correlations between function and bother subscales within domains were high (r >0.60). Correlations between different primary domains were consistently lower, indicating that these domains assess distinct HRQOL components. EPIC domains had weak to modest correlations with the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12), indicating rationale for their concurrent use. Moderate agreement was observed between EPIC domains relevant to the Functional Assessment of Cancer Therapy Prostate module (FACT-P) and the American Urological Association Symptom Index (AUA-SI), providing criterion validity without excessive overlap. CONCLUSIONS: EPIC is a robust prostate cancer HRQOL instrument that complements prior instruments by measuring a broad spectrum of urinary, bowel, sexual, and hormonal symptoms, thereby providing a unique tool for comprehensive assessment of HRQOL issues important in contemporary prostate cancer management.

Aged↗

PubMed2000

Overall survival after prostate-specific-antigen-detected recurrence following conformal radiation therapy.

PURPOSE: To study the significance, in terms of overall and cause-specific survival, of biochemical failure after conformal external-beam radiation therapy (RT) for prostate cancer. METHODS AND MATERIALS: Of the 1844 patients in the Radiation Oncology prostate cancer database, 718 were deemed eligible. Patients excluded were those with N1 or M1 disease, those treated after radical prostatectomy, those who received hormone therapy before radiation therapy, and those who died, failed clinically, or had no PSA response in the first 6 months after RT. Patients included were required to have a minimum of 2 post-RT PSAs separated by at least 1 week. Biochemical relapse was defined as 3 consecutive PSA rises. This resulted in 154 patients with biochemical failure. Survival was calculated from the third PSA elevation. The rate of rise of PSA was calculated by fitting a regression line to the four rising PSAs on a ln PSA vs. time plot. RESULTS: There were 41 deaths among the 154 patients with failure in 23 of the 41 due to prostate cancer. The overall survival after failure was 58% at 5 years, while the cause-specific failure was 73% at 5 years. Among the 154 failures, several factors were evaluated for an association with overall survival: age at failure, pre-RT PSA, PSA at second rise, PSA nadir, time from RT to failure, time to nadir, Gleason score, T-stage, and rate of rise, both from the nadir and from the beginning of the rise. None of these factors were significantly associated with an increased risk of death. As expected, the group of patients with biochemical failure have significantly worse prognostic factors than those without biochemical failure: median pre-RT PSA 15.9 vs. 9.0 (p < 0.001), and Gleason score of 7 or greater for 48% of subjects vs. 40% (p = 0.1). Relative PSA rise and slope of ln PSA vs. time were associated with cause-specific mortality (p < 0.001 and p = 0.007, respectively). CONCLUSION: Overall survival after conformal radiotherapy for prostate cancer remains high 5 years after biochemical failure. This high survival rate occurs even though the group of patients with biochemical failure has worse than average adverse preradiation prognostic factors. Thus, although biochemical failure can identify patients who have recurrent disease after RT, the ultimate relationship between this endpoint and death remains to be better defined.

Aged↗

PubMed2000

Sustained activity and release of leuprolide acetate from an in situ forming polymeric implant.

The primary objective of this study was to evaluate the effect of drug loading on the release of leuprolide acetate from an injectable polymeric implant, formed in situ, and efficacy of the released drug in suppressing serum testosterone levels in dogs for at least 90 days. An additional objective was to compare the optimum implant formulation with a commercial microsphere product. Evaluated implant formulations contained 45% w/w 75/25 poly (DL-lactide-co-glycolide) polymer having an intrinsic viscosity of 0.20 dL/g, dissolved in N-methyl-2-pyrrolidone. Irradiated polymer solution was mixed with leuprolide at different drug loads (3%, 4.5%, and 6% w/w) prior to subcutaneous administration to dogs. Dog serum was analyzed for testosterone (RIA) and leuprolide (LC/MS/MS) levels and comparisons within the three implant formulation groups were made. Varying the drug load did not significantly affect the release of leuprolide or efficacy of the implant formulation. Thus, the 6% w/w formulation with the smaller injection volume was selected for comparison with the commercial LUPRON Depot product, which was administered intramuscularly at a similar dosage. These comparisons of serum testosterone and leuprolide levels showed no significant difference in the pharmacologic efficacy even though drug levels were different at a number of points. This was mainly due to associated high standard deviations. Based on these studies, the 6% w/w leuprolide implant formulation was considered to be a suitable candidate for further development. Additional benefits of this system include its simple manufacturing and lower costs.

Animals↗

PubMed2000

Restored expression of fragile histidine triad protein and tumorigenicity of cervical carcinoma cells.

BACKGROUND: Allelic losses in the short arm of chromosome 3 are common in cervical carcinomas. The fragile histidine triad (FHIT) gene at chromosome region 3p14.2 is a candidate tumor suppressor gene that may play a role in cervical tumorigenesis. We and others have identified aberrant FHIT transcripts and frequent loss of Fhit protein expression in primary cervical cancers and high-grade noninvasive lesions but not in normal cervical tissues. The altered expression of FHIT may be due to somatic mutations or integration of human papillomavirus DNA at the FHIT locus. The purpose of this study was to determine whether ectopic expression of Fhit can suppress the tumorigenic properties of cervical cancer cells. METHODS: We employed infection with recombinant retroviruses as well as transfection of plasmid DNA to restore Fhit protein expression in cervical cancer cell lines lacking full-length FHIT transcripts and endogenous Fhit protein. The effects of Fhit expression on tumor cell morphology, anchorage-independent growth, and tumorigenicity in nude mice were examined. RESULTS: Stable overexpression of Fhit had no discernible effect on the tumorigenic properties of two cervical carcinoma cell lines or on a lung carcinoma cell line previously reported by others to be suppressed for tumorigenicity by Fhit. CONCLUSIONS: Restoration of Fhit expression does not suppress anchorage-independent growth or tumorigenicity of cervical carcinoma cell lines. However, it remains possible that FHIT inactivation may be important early in cervical tumor progression or that FHIT may suppress tumorigenesis in ways distinct from those measured by the assays employed in this study.

Acid Anhydride Hydrolases↗

PubMed2000

Parameters affecting the efficacy of a sustained release polymeric implant of leuprolide.

The objective of this study was to evaluate the formulation parameters critical to the efficacy of an injectable polymeric implant of leuprolide acetate, formed in situ, in suppressing and maintaining serum testosterone levels of animals in the range 0.5 ng/ml for over 90 days. The formulation evaluated contained 45% (w/w) 75/25 poly (DL-lactide-co-glycolide) polymer having an intrinsic viscosity of 0.20 dl/g, dissolved in 55% (w/w) N-methyl-2-pyrrolidone with 3% (w/w) leuprolide acetate added either as a homogeneous solution or a two-part suspension (A/B) system, in which the drug was dispersed within the polymer solution immediately prior to use. The formulation parameters evaluated in this study included polymer molecular weight, polymer concentration, and drug loading. Both rat and dog models were used to evaluate efficacy. Serum testosterone was assayed by radioimmunoassay to determine efficacy, and retrieved implants from the rats at the termination of the study were analyzed by HPLC for residual drug content to determine the extent of drug release. With the candidate formulation, testosterone levels in dogs diminished to the targeted levels of 0. 5 ng/ml by day 14 and remained suppressed up to day 91, reproducing the results seen in rats. Variations in polymer concentration (40-50%), and drug load (3-6% (w/w)) did not have a significant effect on the apparent level and duration of efficacy. However, employing lower molecular weight polymer decreased the duration of efficacy of the formulation.

Animals↗

PubMed2000

Preliminary in vivo studies on the osteogenic potential of bone morphogenetic proteins delivered from an absorbable puttylike polymer matrix.

This article describes preliminary in vivo studies evaluating the osteogeneic potential of bone morphogenetic proteins (BMPs) delivered from an absorbable puttylike polymer matrix. In the first study, bovine-derived bone morphogenetic proteins were incorporated in an polymer matrix consisting of 50:50 poly(DL-lactide-co-glycolide) dissolved in N-methyl-2-pyrrolidone. The matrix was implanted in an 8 mm critical-size calvarial defect created in the skull of adult Sprague-Dawley rats (n = 5 per treatment group). After 28 days, the implant sites were removed and examined for new bone formation, polymer degradation, and tissue reaction. Gamma-irradiated polymer matrices appeared to give more bone formation than nonirradiated samples (histological analysis; 2. 76 + 1.34 mm(2) of bone versus 1.30 + 0.90 mm(2) of bone, respectively and x-ray analysis; 27.2 + 15.9 mm(2) of bone versus 20. 7 + 16.7 mm(2) of bone, respectively) and less residual polymer (0.0 + 0.0 versus 0.2 + 0.4, respectively). The polymer implants with bone morphogenetic protein also gave less inflammatory response than the polymer controls (gamma irradiated polymer/BMP = 1.8 + 0.4 and nonirradiated polymer/BMP = 1.2 + 0.4 versus polymer only = 3.0 + 1. 2, respectively). However, despite trends in both the x-ray and histological data there was no statistical difference in the amount of new bone formed among the four treatment groups (P > 0.05). This was most likely due to the large variance in the data scatter and the small number of animals per group. In the second animal study, bovine-derived BMPs and the polymeric carrier were gamma irradiated separately, at doses of 1.5 or 2.5 Mrad, and their ability to form bone in a rat skull onlay model was evaluated using Sprague-Dawley rats (n = 5 per treatment group). Histomorphometry of skull caps harvested 28 days after implantation showed no significant differences as compared to non-irradiated samples, in implant area, new bone area, and percent new bone (P > 0.05). These results suggest gamma irradiation may be useful in sterilization of the bovine-derived BMPs and the polymeric carrier for potential bone repair and/or regeneration applications.

Animals↗

PubMed2000

Sustained suppression of pituitary-gonadal axis with an injectable, in situ forming implant of leuprolide acetate.

The objective of these studies was to develop a leuprolide acetate depot based on an in situ forming drug delivery system (Atrigel(R)) to suppress the pituitary-gonadal axis and in turn the serum testosterone to chemical castration levels for a period of at least 3 months. Formulations with biodegradable lactide/glycolide copolymers that varied in molecular weight, lactide/glycolide ratio, and hydrophilicity were evaluated in rats for their efficacy by measuring serum testosterone levels. The effect of polymer irradiation was also investigated. Molecular weight of the polymers was characterized by gel-permeation chromatography, and retrieved implants at the termination of animal studies were assayed for residual drug content by high-performance liquid chromatography. These initial rat studies showed that a formulation containing a 75/25 lactide/glycolide copolymer dissolved in N-methyl-2-pyrrolidone with 3% w/w leuprolide acetate suppressed serum testosterone for a period of 3 months or longer. This formulation with its advantages of biodegradability, biocompatibility, ease of injection, and no need for removal after use should be beneficial in treating patients with hormonal-dependent prostate and mammary cancers, endometriosis, and precocious puberty. In addition, this formulation with its simple manufacturing process is expected to provide an economic benefit to the user compared with products currently available on the market.

Animals↗

PubMed2000

Improving postoperative MR imaging of pituitary macroadenomas: comparison of full and reduced dose of gadopentetate dimeglumine.

The aim of this study was to evaluate the efficacy of contrast-medium (CM)-ehanced MR imaging of operated pituitary macroadenomas with reduced dose of gadopentetate dimeglumine. In a prospective study 18 patients were examined with coronal T1-weighted MR imaging prior to and following intravenous CM injections. Two sets of contrast-enhanced coronal images were obtained in each patient; the first set after 50% of the recommended dose of 0.1 mmol/kg body weight (b.w.) had been administered, and the second set immediately after additional CM had been given to make up a total dose of 0.1 mmol/kg b.w. The images were evaluated by three neuroradiologists. The SIPAP classification system was used to evaluate tumour extension, whereas tumour margin conspicuity was scored using an arbitrary scale of 1-5 (1 = indistinct, 5 = well defined). Signal intensity measurements obtained from the most enhancing part of the adenomas demonstrated increased enhancement with increased CM dose. Tumour delineation scores were significantly better on the reduced- and full-dose images than on pre-CM injection images, but, with one exception, tumour extension was identified as the same on all imaging sequences. Postoperative MR imaging of large macroadenoma residues can routinely be performed without intravenous CM. When CM is indicated a reduced dose of gadopentetate dimeglumine should provide sufficient diagnostic information.

Adenoma↗

PubMed2000

Prospective assessment of patient reported urinary continence after radical prostatectomy.

PURPOSE: Reported urinary continence rates after radical prostatectomy vary. Although modifications of radical prostatectomy meant to improve outcome, such as nerve sparing or bladder neck preservation, are in widespread use, to our knowledge evidence to support these practices based on patient report is scant. We evaluated the potential effects of nerve sparing and bladder neck preservation on urinary continence after radical prostatectomy, and assessed the impact of various urinary continence definitions on the observed outcome. MATERIALS AND METHODS: We prospectively evaluated a cohort of men with prostate cancer who elected surgery with and without nerve sparing, and bladder neck preservation as primary therapy. A total of 482 men completed a brief urinary continence questionnaire preoperatively and postoperatively at a median followup of 18 months. Urinary continence was followed prospectively using the questionnaire and patient reported urinary continence recovery was based on 3 definitions of continence. RESULTS: Median time to continence recovery based on patient reporting was significantly shorter in the nerve sparing than in the nonnerve sparing group when continence was defined as no urinary leakage (5.3 versus 10.9 months, p <0.01). A multivariate model controlling for baseline factors revealed that significant predictors of continence outcome were preoperative continence, patient age, nerve sparing and the interaction of nerve sparing with age (p <0.05). The definition of urinary continence also affected outcome. CONCLUSIONS: The nerve sparing technique of radical prostatectomy was associated with improved recovery of urinary continence in an age dependent manner, whereas bladder neck preservation was not beneficial. Patient age and the sensitivity of the incontinence definitions, as reflected by the associated variable rates of preoperative baseline incontinence, are significant contexts for interpreting urinary function data after radical prostatectomy. These factors may partially explain the variation in continence rates in the literature.

Adult↗

PubMed2000

Gender-specific effects of modifiable health risk factors on coronary heart disease and related expenditures. HERO Research Committee. Health Enhancement Research Organization.

There is a general lack of health-related research focusing on gender-specific differences within a working population. This research attempts to address that void. Our study relied on the Health Enhancement Research Organization (HERO) database, which consists of claims, enrollment information, and health risk data for 39,999 employees of six large employers. The research objective was to determine the gender-specific association between coronary heart disease (CHD) and (1) the prevalence of modifiable health risks and (2) medical expenditures. To accomplish this, the International Classification of Diseases, 9th Revision-Clinical Modification and Current Procedural Terminology codes were used to identify 2452 employees with CHD within the HERO database. These individuals made up the study group, which included 66% male and 34% female participants. Health risk data were obtained from voluntary participation in a health risk appraisal and biometric evaluation provided by the employers. Health risks evaluated were tobacco use, hypertension, obesity, elevated cholesterol, high blood glucose, sedentary lifestyle, stress, depression, and excessive use of alcohol. Descriptive and multivariate statistical techniques were used to analyze the HERO database. We found that obesity was the most consistent predictor of CHD. It was number one (of 10 health risks) in the male and female group, number two in the male-only group, and number one in the female-only group. High stress was the second most consistent predictor. There was no such consistency relative to medical expenditures. This lack of consistency across the male and female groups relative to the association between health risks and medical expenditures was demonstrated for nearly all other health risks evaluated. This study suggests that within a group of employees with CHD, there are important similarities and differences between men and women with respect to the prevalence of risk factors and the association between health risks and medical expenditures.

Adult↗