Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml.

PURPOSE: Serum prostate specific antigen (PSA) is widely used as a guide to initiate prostatic biopsies and to follow men older than 50 years old with and without prostate cancer. However, benign prostatic hyperplasia (BPH) is a common cause of serum PSA values between 2 and 10 ng./ml. A better understanding of the relationships among serum PSA, prostate cancer and BPH is important. MATERIALS AND METHODS: A total of 875 men underwent radical prostatectomy at our institution between December 1984 and January 1997. Of these men 784 had a serum PSA of 2 to 22 ng./ml., including 579 with the largest cancer located in the peripheral zone of the prostate. Of the 579 men 406 had serum PSA followups for greater than 3 years after radical prostatectomy. We examined Pearson correlations (R2) between preoperative serum PSA, and the volume of Gleason grades 4/5 and 3 to 1 cancer in 784 men, separating peripheral zone from transition zone cancers. We used broken line regression with break points of 7 and 9 ng./ml. preoperative PSA to summarize the relationship of each PSA doubling to 5 different morphological variables in 579 men with peripheral zone cancer. A 9 ng./ml. break point was used for prostate weight. Trend summaries with a local regression line for the relationships between 6 morphological variables and PSA were superimposed on full scatterplots of the 579 men with PSA less than 22 ng./ml. Cox proportional hazard models were used to examine 5-year PSA failure-free probabilities based on 406 men with minimal PSA followups greater than 3 years at break points of 7 to 9 ng./ml. PSA. RESULTS: Pearson correlation between cancer volume and preoperative serum PSA in 875 men was weak (r2 = 0.27) and driven by large cancers with serum PSA greater than 22 ng./ml. For peripheral zone cancer the overall R2 x 100 for 641 men with low and high grade cancer was 10% and only 3% for low grade cancer, that is almost no PSA produced by these peripheral zone cancers enters the serum. All morphological variables changed at rates of doubtful medical significance below a PSA of 7 to 9 ng./ml. but at rates that were significantly worse above 9 ng./ml. R2 for these relationships was never greater than 15%. Large individual morphological variations at all levels of PSA emphasize the serious limitation of PSA as a predictor of prostate cancer morphology. Below 9 ng./ml. prostate weight increased by 21% for each doubling of PSA but above 9 ng./ml. the increase was only 4.8%. CONCLUSIONS: Preoperative serum PSA has a clinically useless relationship with cancer volume and grade in radical prostatectomy specimens, and a limited relationship with PSA cure rates at preoperative serum PSA levels of 2 to 9 ng./ml. Trend summaries for prostate weight on broken line regression showed that below 9 ng./ml. BPH is a strong contender for the cause of PSA elevation, constituting the primary cause of the over diagnosis of prostate cancer.     

Ischemic preconditioning and Na+/H+ exchange inhibition improve reperfusion ion homeostasis

BACKGROUND: Intramyocyte sodium (Na+) increases during ischemia and reperfusion, which causes myocardial calcium (Ca2+) uptake and leads to myocyte injury or death. This study determines if ischemic preconditioning and myocyte sodium-hydrogen ion (Na+-H+) exchange (NHE) inhibition decreases Na+ gain that otherwise occurs with cardioplegic arrest and reperfusion. METHODS: Pigs had 1 hour of cardioplegic arrest followed by reperfusion. Group 1 had no intervention (controls). Group 2 received dimethyl amiloride (DMA, an NHE inhibitor), and group 3 had ischemic preconditioning before cardioplegic arrest. Precardioplegia to postreperfusion change in intramyocyte ion content was measured with atomic absorption spectrometry. The time to initial electrical activity and number of defibrillations needed to establish an organized rhythm postreperfusion were used as electrophysiologic variables to measure ischemia-reperfusion injury. RESULTS: Intramyocyte Na+ content for group 1 increased from 45.9+/-6.7 to 61.9+/-22.5 micromol/g (p = 0.02). Group 2 had an insignificant decrease in intramyocyte Na+ of 27.7+/-19.58 micromol/g (p = 0.06), and group 3 had an insignificant decrease of 10.8+/-46.33 micromol/g (p = 0.48). Interstitial water increased significantly in all groups, but there were no significant increases in intramyocyte water content. Electrophysiologic recovery was similar for all three groups. CONCLUSIONS: The NHE inhibition and ischemic preconditioning each eliminated the increase in intramyocyte Na+ content that otherwise occurred with cardioplegic arrest and reperfusion in this porcine model. Because their mechanisms are distinct, it is possible that an additive beneficial effect against ischemia-reperfusion injury can be achieved by using NHE inhibition together with a preconditioning stimulus as prereperfusion therapy.     

Community reintegration following acquired brain injury

Objective: To evaluate the interventions and strategies used to enable transition from acute care or post-acute rehabilitation to the community following brain injury.

Methods and main outcomes: A systematic review of the literature from 1980-2005 was conducted focusing on ABI rehabilitation. Five major aspects of community reintegration, including: independence and social integration, caregiver burden, satisfaction with quality of life, productivity and return to driving were considered.

Results: With the exception of one, the majority of interventions are supported by only limited evidence, denoting an absence of randomized controlled trials (RCTs) in the literature. Of 38 studies evaluated for this review, only one RCT was found. That RCT provided moderate evidence that behavioural management, coupled with caregiver education, did not help to improve caregiver burden. Conclusions: Further research, using an interventional approach, is required to advance the evidence base of reintegration into the community following brain injury.     

The outcome of children with intractable seizures: a 3- to 6-year follow-up of 67 children who remained on the ketogenic diet less than one year

PURPOSE: To determine the long-term outcome of children with difficult-to-control seizures who remained on the ketogenic diet for <1 year. METHODS: Between 1994 and 1996, 150 children with epilepsy, refractory to at least two medications, initiated the ketogenic diet according to the Hopkins protocol. Three to six years after diet initiation, all the families were contacted by telephone or questionnaire to assess their child's current seizure status, medications, and therapies. RESULTS: Sixty-seven children discontinued the diet within 1 year of initiation. Follow-up data were available for 54 of these children. Ten subsequently had surgery, and three underwent VNS implantation. These operated-on children were significantly more likely to be >50% controlled at follow-up than were those managed with medications alone (p < 0.05). A statistically significant difference in long-term outcome was noted between those who responded while on the diet, even if they discontinued it before 1 year, and those who did not (p < 0.05), but no statistical correlation was found between length of time that they had remained on the diet and long-term prognosis. CONCLUSIONS: Almost half of the children who discontinued the diet during the first year had a decrease in seizures when assessed 3-6 years later. Twenty-two percent of these had become seizure free without surgery. We were unable to ascertain whether this may have been due to new medications. Those who saw some improvement while on the diet were more likely to have a favorable long-term outcome. Resective surgery, in children who were candidates, or vagal nerve stimulation (VNS) implantation, was more likely to result in significant seizure improvement than was management with medications alone. Whether or not the diet was effective, most families did not regret trying it and would recommend it to others.     

Influence of Activity on Quality of Life Scores After RYGBP

Gastric bypass is one of the medically acceptable interventions for weight loss for the obese. Quality of life greatly improves after surgery. Most improvements in quality of life (QOL) after these surgeries are attributed to the weight loss. Few studies have demonstrated any contribution of other variables to positive outcomes in QOL. The purpose of this study was to suggest variables that improve QOL in this post-surgical population. The Arizona Activity Frequency Questionnaire, the Arizona Food Frequency Questionnaire, and the SF-36 survey were sent to all of the Roux-en-Y gastric bypass procedure (RYGBP) patients who had surgery 1–5 years prior to the study and performed through the same bariatric surgery center (n = 805; respondents = 265; 33%). Analysis was performed through ANOVA testing to determine relationships between selected behaviors and the SF-36 of the respondents. Comparisons of differences in SF-36 scores were analyzed using the variables of hours of activity/day (HOAD) and energy in activity/day (EEAD). Patients with more EEAD and HOAD demonstrated significantly better SF-36 scores in both mental component and physical component scores (p = 0.05) when compared to those with less EEAD or HOAD. Outcomes measured by the SF-36 tool were improved after RYGBP, if the patient expended more energy/day or was active more hours/day. The post-bariatric surgery populations will have improved QOL if the patients expend more energy and are active more hours as demonstrated in activity/day after their surgery.     

The Effect of Total Knee Arthroplasty on Knee Joint Kinematics and Kinetics During Gait

This study determined how total knee arthroplasty (TKA) altered knee motion and loading during gait. Three-dimensional kinematic and kinetic gait patterns of 42 patients with severe knee osteoarthritis were collected 1 week prior and 1-year post-TKA. Principal component analysis extracted major patterns of variability in the gait waveforms. Overall and midstance knee adduction moment magnitude decreased. Overall knee flexion angle magnitude increased due to an increase during swing. Increases in the early stance knee flexion moment and late stance knee extension moment were found, indicating improved impact attenuation and function. A decrease in the early stance knee external rotation moment indicated alteration in the typical rotation mechanism. Most changes moved toward an asymptomatic pattern and would be considered improvements in motion, function, and loading.     

Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

BACKGROUND: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. METHODS: Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. RESULTS: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). CONCLUSIONS: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.     

Why current breast pathology practices must be evaluated. A Susan G. Komen for the Cure white paper: June 2006

Ending breast cancer has long been the mission of Susan G. Komen for the Cure. To this end, the organization has a strong interest and proven track record in ensuring public investment in quality breast health and breast cancer care. Recently, Susan G. Komen for the Cure identified major issues in the practice of pathology that have a negative impact on the lives of thousands of breast cancer patients in the United States. These issues were identified through a comprehensive literature review and interviews conducted in 2005-2006 with experts in oncology, breast pathology, surgery, and radiology. The interviewees practiced in community, academic, and cooperative group settings. Komen for the Cure has identified four areas that have a direct impact on the quality of care breast cancer patients receive in the United States, the accuracy of breast pathology diagnostics, the effects of current health insurance, and reimbursement policies on patients who are evaluated for a possible breast cancer diagnosis, the substantial decrease in tissue banking participation, particularly during a time of rapid advances in biologically correlated clinical science and the role for the Susan G. Komen for the Cure, pathology professional societies and the Federal government in ensuring that breast pathology practices meet the highest possible standards in the United States Concerns surrounding the quality and practice of breast pathology are not limited to diagnostic accuracy. Other considerations include, training and proficiency of pathologists who are evaluating breast specimens, the lack of integration of pathologists in the clinical care team, inadequate compensation for the amount of work required to thoroughly analyze specimens, potential loss in translational research as a result of medical privacy regulations, and the lack of mandatory uniform pathology practice standards without any way to measure the degree of variation or to remedy it.     

The degree of bone mineralization is maintained with single intravenous bisphosphonates in aged estrogen-deficient rats and is a strong predictor of bone strength

The treatment of osteoporotic women with bisphosphonates significantly reduces the incidence of bone fractures to a degree greater than can be explained by an increase in bone mineral density. In this study, 18-month Fischer 344 rats were ovariectomized and treated with a single dose of risedronate (intravenous, iv, 500 microg), zoledronic acid (iv, 100 microg) or continuous raloxifene (2 mg/kg, po, 3x/week). High resolution microCT was used to measure lumbar vertebral bone microarchitecture, the degree of bone mineralization (DBM) and the distribution of mineral. Small angle X-ray scattering was used to investigate mineral crystallinity. We found prolonged estrogen deficiency, reduced trabecular bone volume, and increased micro architecture bone compression strength lowered the degree of mineralization. Treatment with resorptive agents (bisphosphonates>raloxifene) prevented the loss of mineralization, trabecular bone volume and bone compression strength. Crystal size was not changed with OVX or with anti-resorptive treatments. In conclusion, in the aged estrogen-deficient rat model, single intravenous doses of two bisphosphonates were effective in maintaining the compressive bone strength for 180 days by reducing bone turnover, and maintaining the DBM to a greater degree than with raloxifene.