Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials

PURPOSE: Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS: Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS: By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS: Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.     

A comparison of the locomotor stimulant effects of D1-like receptor agonists in mice

Efficacy in stimulating adenylyl cyclase (AC) has traditionally been used to distinguish dopamine D1-like receptor agonists from dopamine D2-like receptor agonists. However, there is a limited association between the effects of D1-like agonists in behavioral assays and their effectiveness at stimulating AC. Other second messenger actions might contribute to the behavioral effects of D1-like agonists, as there is evidence for a link to the hydrolysis of phosphoinositide (PI). The present study compared the locomotor stimulant effects of five D1-like receptor agonists having different efficacies in assays of AC and PI activity. All D1-like agonists produced long-lasting biphasic effects on locomotor activity. SKF 38393, the prototypical partial agonist (based on AC activity), produced limited changes in locomotor activity, whereas the partial agonists SKF 75670 and SKF 77434 produced locomotor stimulant effects that were similar to or greater than those of the full efficacy agonists SKF 82958 and SKF 81297. However, there did not appear to be a relationship between maximal behavioral effects and AC stimulation or PI hydrolysis. The results suggest a complex relationship between the behavioral effects of D1-like agonists and their intrinsic efficacies as measured by AC and /or PI stimulation. Although a limited number of compounds were examined, neither second messenger system alone appears to account fully for these behavioral effects. The current classification of D1-like agonists according to their intrinsic efficacies as defined by AC stimulation needs further scrutiny.     

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.     

The Role of Psychosocial Factors in the Transition to Substance Use: Are They Protective Among Urban Minority Adolescents?

Changes in psychosocial risk and protective factors associated with the onset of substance use were examined in a sample of 556 urban public school sixth graders. General linear modeling analyses indicated that students who did not use substances by the end of sixth grade consistently had higher scores on protective factors than did students who were already using substances at the beginning of sixth grade. Students who began to use during the school year were in flux with scores similar to nonusers at Time 1 and scores closer to early users by Time 2. These findings suggest that interventions which focus on skill enhancement during the transition to middle school may be effective at delaying the onset of substance use. Editors' Strategic Implications: The authors find the same protective factors in this urban, primarily African American sample that are typical in suburban, White samples. Developmentalists and school officials will find interesting the changing effects of protective factors against early substance use during the transitional sixth grade year.     

Inhibition of heart transplant injury and graft coronary artery disease after prolonged organ ischemia by selective protein kinase C regulators

OBJECTIVE: Transplanted hearts subjected to prolonged ischemia develop ischemia-reperfusion injury and graft coronary artery disease. To determine the effect of delta-protein kinase C and -protein kinase C on ischemia-reperfusion injury and the resulting graft coronary artery disease induced by prolonged ischemia, we used a delta-protein kinase C-selective inhibitor peptide and an -protein kinase C-selective activator peptide after 30 or 120 minutes of ischemia. METHODS: Hearts of piebald viral glaxo (PVG) rats were heterotopically transplanted into allogeneic August Copenhagen Irish (ACI) rats. After cardioplegic arrest of the donor heart, -protein kinase C activator was injected antegrade into the coronary arteries. Hearts were procured and bathed in -protein kinase C activator, and before reperfusion, delta-protein kinase C inhibitor was injected into the recipient inferior vena cava. Controls were treated with saline. To analyze ischemia-reperfusion injury, grafts were procured at 4 hours after transplantation and analyzed for superoxide generation; myeloperoxidase activity; tumor necrosis factor alpha, interleukin 1beta, and monocyte/macrophage chemoattractant protein 1 production; and cardiomyocyte apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase 2, 3, 8, and 9 activity. To analyze graft coronary artery disease, another set of animals underwent equal ischemic times and treatment strategies and then after 90 days were analyzed for graft coronary artery disease indexes. RESULTS: All measures of ischemia-reperfusion injury and graft coronary artery disease after 120 minutes of ischemia in the saline-treated group were significantly increased relative to those observed after 30 minutes of ischemia. It is important to note that all ischemia-reperfusion injury parameters and graft coronary artery disease indexes decreased significantly in the protein kinase C regulator-treated group in comparison to saline-treated controls; additionally, these values were equivalent to those in saline-treated controls with 30 minutes of ischemia. CONCLUSIONS: Combined treatment with -protein kinase C activator and delta-protein kinase C inhibitor reduces ischemia-reperfusion injury and decreases the resulting graft coronary artery disease induced by prolonged ischemia.     

Change in serum prostate specific antigen concentration after holmium laser enucleation of the prostate: a marker for completeness of adenoma resection?

BACKGROUND AND PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a well-established technique for the treatment of benign prostatic hyperplasia (BPH). To date, changes in serum prostate specific antigen (PSA) after HoLEP have not been published. We hypothesized that HoLEP produces a diminution in PSA similar to that produced by the gold-standard therapies for BPH. To test this hypothesis, we have examined PSA data before and after HoLEP from two institutions performing high volumes of this procedure. PATIENTS AND METHODS: Between August 1998 and September 2004, 509 HoLEPs were performed at two institutions for which complete PSA data were available. Preoperative demographic and transrectal ultrasonography (TRUS) volume measurements were recorded; postoperative pathology and TRUS volume were obtained. Change in PSA as a function of the weight of prostate resected and the relation of preoperative TRUS volume to PSA was determined. RESULTS: The average weight of adenoma resected was 49.8 g (range 5-300 g) in the McGill group and 90.4 g (range 7.9-312 g) in the Methodist Hospital group. The mean decrease in PSA was 81.7% in the McGill group (range 6.0-1.1 ng/mL; P < 0.0001) and 86.0% in the Methodist Hospital group (range 8.6-1.2 ng/mL; P < 0.0001). Log transformed preoperative PSA correlated well with TRUS volume (r = 0.45), as did the weight of adenoma resected with absolute change in PSA (r = 0.38). The TRUS volume decreased significantly, from 111.9 cc to 26.5 cc, in the Methodist Hospital group (P < 0.0001). CONCLUSION: The HoLEP procedure produces a significant diminution in PSA that correlates well with the weight of adenoma resected. Measurement of PSA may be a useful tool for the objective assessment of ablative therapies for BPH, as the reduction in PSA corresponds well with the amount of adenoma removed.     

Well leg compartment syndrome after pelvic and perineal surgery in the lithotomy position

Objective: Lower limb compartment syndrome after prolonged surgical procedures performed in the lithotomy position is a rare but potentially devastating complication. It is recognised after urological, colorectal, and gynaecological procedures. Sixteen cases of compartment syndrome after urological surgery have been reported. The objective of this study was to estimate the incidence of this complication in urological practice and identify risk factors for its development. Design: A postal survey of UK consultant urologists was conducted. Results: Replies were received from 261 consultants. In total there were 65 cases of compartment syndrome. Compartment syndrome occurred after radical cystectomy and urinary diversion in 51 cases and was rare in procedures lasting less than four hours. The incidence of compartment syndrome after cystectomy was estimated at around 1 in 500 cases. Risk factors for its development included perioperative blood loss, peripheral vascular disease, and obesity. Conclusions: Compartment syndrome after use of the lithotomy position may be more common than is generally appreciated and has been underreported in the past. All staff should be aware of this serious complication and adopt strategies for its avoidance.     

Genetic variation in the progesterone receptor gene and ovarian cancer risk

Evidence suggests a role for progesterone in ovarian cancer development. Progesterone exerts its effect on target cells by interacting with its receptor. Thus, genetic variations that may cause alterations in the biologic functions of the progesterone receptor can potentially contribute to individual susceptibility to ovarian cancer. Using a population-based, case-control study, the authors genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A, G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034 controls living in New Hampshire and eastern Massachusetts (May 1992-November 2002). Odds ratios and 95% confidence intervals were calculated to evaluate associations with ovarian cancer. No associations were observed between the +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse association was observed between the V660L variant and ovarian cancer (odds ratio = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after adjustment for potential confounders. Five haplotypes occurred with greater than 5% frequency, and the haplotype carrying the V660L variant had a significant association with ovarian cancer (odds ratio = 0.76, 95% confidence interval: 0.62, 0.92). Associations were similar after stratifying by ovarian cancer histologies and risk factors.     

The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue

Successful cryopreservation of human hepatocytes is important to establish hepatocyte banks for clinical use or in vitro research. The availability of donor tissue from unused liver segments/lobes and non-heart-beating donors (NHBD) has provided newer sources of hepatocytes. The quality of hepatocytes at the time of cryopreservation is important as cells isolated from liver tissue of borderline quality may not withstand the stresses associated with cryopreservation and subsequent thawing. Human hepatocytes were cryopreserved after isolation from mainly donor tissues (n = 40). In vitro assessment of the viability and function of the fresh and thawed cryopreserved hepatocytes was performed. Viability, attachment efficiency, enzyme activity, and albumin production of hepatocytes were all significantly decreased, and LDH leakage significantly increased, on thawing after cryopreservation. The viability of cryopreserved hepatocytes isolated from tissue rejected for orthotopic liver transplantation (36 +/- 15%) was significantly lower than those isolated from tissue where part was used for liver transplantation (47 +/- 14%, p = 0.002), but there were no significant differences in functional parameters. The viability of cryopreserved hepatocytes isolated from NHBD tissue (29 +/- 9%, p = 0.001) and from steatotic donor tissue (35 +/- 11%, p = 0.019) was significantly lower than those isolated from normal donor tissue (49 +/- 14%). There was no difference in functional parameters, except for albumin production of hepatocytes from NHBD tissue (2.9 +/- 1.0 microg/h/mg protein) being significantly lower than those from normal donor tissue (4.8 +/- 2.8 microg/h/mg protein, p = 0.03). The viability and attachment efficiency of cryopreserved hepatocytes isolated from liver tissue from resections for tumors was significantly higher, and the LDH leakage significantly lower, than those isolated from all donor tissue. Hepatocytes isolated from NHBD and steatotic tissue were more vulnerable to the effects of cryopreservation. Further research is required to improve hepatocyte isolation and cryopreservation protocols for different types of liver tissue.     

A primary healthcare strategy in disaster situations

The present article describes the experience of the Cuban Medical Team in the Colombian Coffee Area after the earthquake of January 25, 1999. The interventions were directed at the areas of primary health care, primary environmental care, environmental health, and epidemiological surveillance, bearing in mind the organization of earthquake victims sheltered in emergency settlements in the affected municipality. Active epidemiological surveillance showed that the main causes of morbidity were acute diarrheic diseases, acute respiratory infections, and skin diseases. Evaluation of the settlements showed a correlation between poor environmental health conditions and associated diseases. The results of this field study could serve as a guide for health professionals in the event of disasters and displaced populations.