Early Care and Education Professionals' Breastfeeding Knowledge and Practices Before and After an E-Learning Program.

Objective: To assess early care and education professionals' breastfeeding knowledge and practices before and after an e-learning program. Participants: Early care and education professionals from New Hampshire (U.S.A.) licensed child care programs were invited to complete a pre-assessment followed by a 90-minute e-learning breastfeeding program. Three months post-training, participants were invited to complete the post-assessment. Analysis: McNemar tests were used to assess changes from pre-post-assessment for dichotomous variables. McNemar-Bowker tests were used to determine differences from pre-post for variables with more than two categories. When the McNemar-Bowker test was significant, a multiple comparison correction (Bonferroni) was used. Results: 114 participants completed the e-learning program and pre-post assessment. Results showed significant improvement from pre-post in 10 of 15 breastfeeding knowledge questions related to health of baby, mother and child care centers, economics, and environmental impact. There were significant changes from pre-post in 24 of 50 breastfeeding practice questions in handling breast milk, promoting breastfeeding, and supporting mothers. Conclusions and Implications: This study indicates improvement in early care and education professionals' breastfeeding knowledge and practices; however, opportunities exist to design targeted initiatives to further strengthen practices that support breastfeeding families in the child care environment.

Critical assessment of the anterolateral thigh flap donor site.

BACKGROUND: The free anterolateral thigh flap (ALT) is now used as a 'workhorse flap'. The donor site morbidity is thought to be minimal, although most evidence derives from questionnaire-based studies rather than rigorous objective clinical assessment. In particular, robust quantitative data on thigh sensibility and quadriceps function is lacking. The aim of this study was to provide a comprehensive clinical assessment of donor site morbidity. METHODS: We performed a prospective study of consecutive free ALT perforator flaps performed at Salisbury Foundation Trust between March 2008 and April 2010. The donor site was assessed at six months including a questionnaire (symptoms, function), scar analysis (Vancouver Scar Scale, VSS), and evaluation of quadriceps power and lateral thigh sensibility (compared with the contralateral unoperated thigh). RESULTS: One hundred ALT flaps were performed on 97 patients (mean age 46.8 years). The donor site was closed directly in 88 cases and using a split skin graft in 12 cases. At follow-up (n=68), tingling was the most common reported symptom (59%), whereas pain, itching and muscle herniation were reported infrequently. Donor site scars were mostly flat, pale and soft but widened. Pathological scarring was rare. Sensibility was reduced in donor thighs (p<0.001) and correlated with flap width but peak quadriceps contraction was similar between donor and unoperated thighs. CONCLUSIONS: There was a high throughput and diverse application of ALT flap reconstructions during the study period. Reduced sensibility was common around the scar but rarely troublesome. Quadriceps function was not affected even when dissection of intramuscular perforators was required. The ALT is a versatile flap that can deliver a large skin paddle with minimal impact on thigh function.

Costs and coding--free-flap reconstruction in lower-limb trauma.

INTRODUCTION: The provision of a complex lower-limb trauma service has significant resource implications. This financial burden is not recognised by the current fixed price tariff system (Payment by Results). The aim of this study was to compare the actual costs of treatment with reimbursement. METHODS: We conducted a prospective study in two large regional plastic surgery centres in the UK, Salisbury Foundation Trust (SFT) and the Frenchay Hospital, Bristol (FH). The total cost of treatment for consecutive patients with complex lower limb trauma requiring free tissue transfer was calculated and compared with the Health Resource Group (HRG) tariff. RESULTS: A cost analysis was performed on 20 patients (10 Salisbury, 10 Frenchay) with open tibial fractures (all grade IIIb Gustillo & Anderson) requiring free-flap reconstruction (15 anterolateral thigh (ALT) flaps, one serratus, one latissimus dorsi (LD), one scapular and two gracilis). The mean treatment cost of performing a free flap was £12792 ± £970 SEM (SFT) and £10953 ± £650 (FH). In both centres, the cost was more than double the HRG tariff (£4220 SFT, £4892 FH, p < 0.05). CONCLUSIONS: Our study highlights the considerable disparity between the cost of managing patients with severe lower-limb trauma and the remuneration by Primary Care Trusts (PCTs). Accurate cost analysis of these cases will allow hospital trusts to negotiate appropriate tariffs with PCTs and develop services, which are cost neutral.

Congenital absence of flexor digitorum superficialis: implications for assessment of little finger lacerations.

Absence of flexor digitorum superficialis function in the little finger is a relatively common congenital anomaly that can complicate assessment of little finger injuries. We reviewed the prevalence of unilateral and bilateral absence of superficialis function in the published literature. In appropriate studies identified (1352 people), the anomaly was unilateral in 92 individuals (6.8%) and bilateral in 81 (6.0%). If superficialis function is absent in one little finger, the probability of absence in the opposite hand is 0.64. If superficialis function is present, the probability of absence in the other little finger is 0.02 (1 in 50). Absence of little finger superficialis function in one hand is therefore not a reliable indicator of this function in the opposite hand.

Rescoring the NIH chronic prostatitis symptom index: nothing new.

The National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) is a commonly used 13-item questionnaire for the assessment of symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). For each item, score ranges are 0-1 (6 items), 0-3 (2 items), 0-5 (3 items), 0-6 (1 item) and 0-10 (1 item). This scoring system is straightforward, but items with wider score ranges are de facto weighted more, which could adversely affect the performance characteristics of the questionnaire. We rescored the NIH-CPSI so that equal weights were assigned to each item, and compared the performance of the standard and rescored questionnaires using the original validation dataset. Both the original and revised versions of the scoring algorithm discriminated similarly among groups of men with CP (n=151), benign prostatic hyperplasia (n=149) and controls (n=134). The internal consistency of the questionnaire was slightly better with the revised scoring, but values with the standard scoring were sufficiently high (Cronbach's >or=0.80). We conclude that although the rescored NIH-CPSI provides better face validity than the standard scoring algorithm, it requires additional calculation efforts and yields only marginal improvements in performance.

Altered monocyte CD44 expression in peripheral arterial disease is corrected by fish oil supplementation.

BACKGROUND AND AIMS: CD44 and its splice variants can be expressed on all leukocytes, conferring adhesive properties and enhancing cellular recruitment to the endothelium during inflammation. CD44 expression is increased in inflammatory conditions such as rheumatoid arthritis and CD44 variant 3 (CD44v3) expression may be associated with inflammation. We have examined CD44 and CD44v3 expression on peripheral blood monocytes from patients with peripheral arterial disease (PAD) and healthy controls. We have also examined the effect of fish oil supplementation on these markers. METHODS AND RESULTS: CD44 and CD44v3 were assessed at baseline and following dietary supplementation with fish oil for 12 weeks in both PAD and control groups. Monocytes from PAD patients had higher CD44 expression than those from controls (median intensity fluorescence (MIF): 480+/-278 vs 336+/-251 (mean+/-SD); p<0.001). Following 12 weeks' dietary supplementation with fish oil, CD44 expression was reduced in PAD patients (MIF: 480+/-278 vs 427+/-262; p=0.05) but not in controls (336+/-251 vs 355+/-280; ns). Monocyte CD44v3 expression was lower in cultured monocytes from PAD patients compared to those from controls (0.15+/-0.15 vs 0.22+/-0.14 OD units; p<0.02). This was increased in the PAD group following fish oil supplementation (0.15+/-0.14 to 0.27+/-0.23 OD units; p<0.001). CONCLUSION: Monocyte CD44 and CD44v3 expression are altered in arterial disease but are returned towards levels seen in control subjects by dietary fish oil supplementation.

X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model.

Deregulation of apoptotic pathways plays a central role in cancer pathogenesis. X-linked inhibitor of apoptosis protein (XIAP), is an antiapoptotic molecule, whose elevated expression has been observed in tumor specimens from patients with prostate carcinoma. Studies in human cancer cell culture models and xenograft tumor models have demonstrated that loss of XIAP sensitizes cancer cells to apoptotic stimuli and abrogates tumor growth. In view of these findings, XIAP represents an attractive antiapoptotic therapeutic target for prostate cancer. To examine the role of XIAP in an immunocompetent mouse cancer model, we have generated transgenic adenocarcinoma of the mouse prostate (TRAMP) mice that lack XIAP. We did not observe a protective effect of Xiap deficiency in TRAMP mice as measured by tumor onset and overall survival. In fact, there was an unexpected trend toward more aggressive disease in the Xiap-deficient mice. These findings suggest that alternative mechanisms of apoptosis resistance are playing a significant oncogenic role in the setting of Xiap deficiency. Our study has implications for XIAP-targeting therapies currently in development. Greater understanding of these mechanisms will aid in combating resistance to XIAP-targeting treatment, in addition to optimizing selection of patients who are most likely to respond to such treatment.

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.

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.

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.

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.

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.

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.

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.

Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease.

Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Fhit protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Fhit protein expression might be associated with tumor progression, immunohistochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix samples. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of progression to invasive carcinoma.

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.

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.

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.

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.

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.