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Psychomotor vigilance testing (PVT) rapidly assesses attention, reaction time (RT), and abnormal vigilance. Thus, PVT may be an adjunct to screening drivers for high-risk obstructive sleep apnea (OSA)/excess daytime sleepiness (EDS).Commercial drivers and emergency responders undergoing occupational examinations took a 10-minute PVT and were instructed to achieve their fastest possible RTs. Participants with maximum RT5 seconds or ≥ 2 "super lapses" (RT ≥ 1000 ms) were categorized as "microsleepers."Among 193 male participants, the 15 microsleepers (8%) were significantly more obese, but not different on age or Epworth Sleepiness Score. Time of day had no effect on RT.PVT is suitable to occupational clinics and can identify otherwise unrecognized, impaired vigilance. Further studies must validate the PVT abnormalities most predictive of OSA/EDS and vehicular crashes, compared to adiposity measures alone.

Surgical blood loss predicts peri-operative outcomes. We have developed and validated Blood Loss Scores to estimate peri-operative blood loss during major abdominal surgery. Surgical blood loss and changes in haemoglobin concentration were recorded intra- and postoperatively for 48 h in 100 patients undergoing radical prostatectomy. Data from the first group (n = 50) were used to derive the Blood Loss Scores which were validated against the data from a second group (n = 50) at three time points (immediately postoperative and 24- and 48-h later). The score, taking into account suction fluid volume and haemoglobin concentration, explained more of the variance in the measured blood loss than the experts' assessment (77% vs 54%, p = 0.05) or the change in haemoglobin concentration (77% vs 11%, p < 0.0001). Addition of the change in haemoglobin concentration improved the estimate for the 24- and 48-h postoperative Blood Loss Scores to explain 78% and 80% of the variance of measured blood loss.

Background— Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins. Methods and Results— We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P Conclusions— The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk- and reward-seeking behaviors, including substance abuse.Endpoints were performance on an array of psychometric tests (including the Eysenck Impulsiveness Scale, the Zuckerman Sensation Seeking Scale, the Gormally Binge Eating Scale, and the Beck Depression and Anxiety Inventory) and on the Balloon Analogue Risk Task (BART).Tertiary narcolepsy referral centers in Leiden (The Netherlands) and Boston (USA).Subjects with narcolepsy with cataplexy (n = 30), narcolepsy without cataplexy (n = 15), and controls (n = 32) matched for age, sex, and smoking behavior.None.There was no difference in risk-taking behavior between narcolepsy with or without cataplexy and the control group, as measured using the BART and the array of questionnaires. However, subjects in the narcolepsy with cataplexy group had significantly higher scores on the Eysenck Impulsiveness Scale (p0.05), with 10.0% categorized as impulsive, compared to 6.7% of the narcolepsy without cataplexy group and none of the controls. Narcoleptics with cataplexy also scored significantly higher than controls on the Binge Eating Scale (p0.05), with moderate or severe binge eating in 23%. On the depression and anxiety scales, all narcolepsy patients, especially those with cataplexy, scored significantly higher than controls.We found that narcoleptics with or without cataplexy generally have normal risk-taking behavior, but narcoleptics with cataplexy were more impulsive and more prone to binge eating than patients without cataplexy and controls. Our findings shed new light on the relation between sleepiness and impulsiveness. Furthermore, rates of depression and anxiety were higher in all narcoleptic subjects. However, using the current methods, no evidence could be found to support the hypothesis that hypocretin deficiency would affect reward-processing in humans.

The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose--response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5-74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9-10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%-57%) and 76% (95% CI, 69%-84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2-8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%-9%), 49% partial response (95% CI, 37%-61%), and 29% stable disease (95% CI, 20%-38%). No difference was seen in bevacizumab dose--response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose--response effect would require confirmation in a prospectively conducted clinical trial.

Purpose: To assess the efficacy of triple combination therapy (TCT) including bevacizumab (BEV), low-fluence photodynamic therapy, and posterior sub-Tenon's triamcinolone acetonide in patients with wet age-related macular degeneration. Methods: This institutional review board-approved retrospective consecutive case series included 31 eyes treated for wet age-related macular degeneration with TCT at the Beth Israel Deaconess Medical Center between June 2004 and November 2008. Outcome measures included visual acuity, retinal thickness as measured by optical coherence tomography, time to retreatment, and complications. Results: Triple combination therapy eyes showed significant 3-month and 6-month improvement in visual acuity of 0.140 ± 0.273 logarithm of the minimum angle of resolution and 0.182 ± 0.383 logarithm of the minimum angle of resolution after treatment, respectively (P = 0.0219 and 0.0470, respectively). Central retinal thickness significantly improved at 3 months (−123.8 ± 102.7 μm), 6 months (−87.7 ± 99.8 μm), and 12 months (−101.6 ± 103.3 μm) on optical coherence tomography. Half of eyes that underwent TCT required retreatment by the conclusion of their follow-up, and eyes that underwent TCT had a 1-year Kaplan-Meier survival rate of 62.1 ± 10.8%. Conclusion: Triple combination therapy (TCT) appears to effectively improve visual acuity and decrease retinal thickness often without need for subsequent retreatment within the first year of follow-up. Further investigation of TCT in prospective trials is warranted.

Background. Patient groups associated with disparities in health care are usually defined on the basis of race, gender or geographic location. Social Adaptability Index (SAI), calculated based on education, marital status, income, employment and substance abuse, has been strongly associated with clinical outcome in other patient populations and may be used to identify individuals at risk. We used data from the United States Renal Data System to evaluate the role of SAI in survival of patients on dialysis. Methods. We used Cox model analyses to study the association between SAI and patient survival in patients with ESRD on dialysis, as well as in the subgroups based on age, race, sex, comorbidites and diabetic status. Results. We analyzed 3396 patients (age of ESRD onset 56.9 6 16.1 years, 54.2% males, 64.2% white, 30.3% African-American). Mean SAI of the entire population was 7.1 6 2.5 (range 0–12 points). SAI was higher in whites (7.4 6 2.4) than in African-Americans (6.5 6 2.5) (analysis of variance, P

Atrial fibrillation prophylaxis with warfarin and strong antiplatelet agent use in cardiovascular diseases has increased the incidence of anticoagulation in the elderly. We studied traumatic intracranial hemorrhage (TICH) in patients ≥55 years of age on anticoagulation and antiplatelet agents in a stable population.We used a Level 1 Trauma Center registry study comparing TICH in patients on anticoagulation drugs during the index periods 1999 to 2000 (T1) and 2007 to 2008 (T2).A total of 526 TICH patients were seen in T1 and T2 (age, 77.6 vs 77.5 years; not significant [NS]), with the rate doubling from 6.2% to 12.3% of all trauma activations (P.01). There was no increase in atrial fibrillation, warfarin use, or CHADS(2) scores in atrial fibrillation patients on anticoagulation therapy. TICH in patients taking antiplatelet agents increased 5-fold (2.2 % vs 10.3%; P .01). Overall TICH mortality rate was the same (12.4% vs 12.2%, NS). TICH mortality among patients on therapeutic warfarin was greater in T1 (26%; P.05), but mortality was similar to TICH in patients not on anticoagulants in T2 (19% vs 12.2%, NS), suggesting treatment improved. Prevalence and mortality of TICH in patients on antiplatelet agents were similar to TICH in patients on warfarin.TICH in patients on anticoagulants is epidemic in patients ≥55 years of age. Despite national trends, our well-served population has not seen an increase in warfarin use for atrial fibrillation. Instead, use of antiplatelet agents has increased and is associated with an increased incidence of TICH.

Expression and role of γ-catenin in colorectal carcinogenesis is not well understood. We aimed at characterizing γ-catenin's expression pattern during colorectal carcinogenesis.The expression pattern of γ-catenin was characterized in adenomas, primary colorectal carcinomas, and their corresponding metastases. Since this descriptive immunohistochemical analysis revealed upregulation of γ-catenin in the invasive front of both primary tumors and metastases, a tissue microarray (TMA) was performed, allowing for correlation of subcellular expression patterns with disease recurrence and cancer-specific survival. Comparison of γ-catenin expression with that of β-catenin was performed.In normal colonic epithelium and adenomas, γ-catenin was weakly expressed at the membrane. In central areas of primary colorectal carcinomas, membranous and cytoplasmatic expression was present, with cytoplasmatic and nuclear upregulation of γ-catenin in the invasive fronts. Expression patterns found in metastases resembled those of their respective primary tumors. Subsequent TMA analysis showed that upregulation of cytoplasmatic γ-catenin in the invasive fronts of curatively resected early T2 and T3 colorectal carcinomas was associated with shortened disease-free survival and an increased risk of death (p=0.003; hazard ratio = 2.98; 95% confidence interval, 1.44-6.18).The correlation of upregulated cellular γ-catenin levels with higher recurrences and impaired survival suggests a tumor promoting role of γ-catenin in colorectal cancer. γ-Catenin may therefore serve as a marker for identifying patients who are at increased risk of disease recurrence who may benefit from closer follow-up and adjuvant therapy.

BACKGROUND Despite a growing literature on patient satisfaction in breast reconstruction, few studies have compared perforator flaps with the more commonly practiced methods. The authors compared four reconstructive techniques and identified factors influencing patient satisfaction. METHODS All patients undergoing postmastectomy breast reconstruction between 1999 and 2006 at a single academic institution were included in our study. A total of 583 patients with tissue expander/implant, latissimus, pedicle transverse rectus abdominis muscle (TRAM), and deep inferior epigastric perforator (DIEP) flap reconstructions received a validated questionnaire on satisfaction, health-related quality of life, and sociodemographic data. RESULTS Patient response was 75 percent, with 439 completed questionnaires including 87 tissue expander/implant, 116 latissimus, and 119 pedicle TRAM and 117 DIEP flap patients. DIEP patients had the highest level of general satisfaction at 80 percent, and pedicle TRAM patients had the highest level of aesthetic satisfaction at 77 percent (p < 0.001 and p < 0.001, respectively). Health-related quality of life and length of time since surgery were identified as significant covariates influencing patient satisfaction. After logistic regression analysis, autologous reconstruction had significantly higher general and aesthetic satisfaction than implant-based reconstruction (p = 0.017 and p < 0.001). Among the autologous reconstructions, abdominal-based flaps had significantly higher general and aesthetic satisfaction than latissimus flaps (p = 0.011 and p = 0.016). When comparing the abdominal-based reconstructions, general and aesthetic satisfaction were no longer statistically significant between pedicle TRAM and DIEP flaps (p = 0.659 and p = 0.198). CONCLUSIONS Autologous, abdominal-based reconstructions had the highest satisfaction rates across all four groups. After logistic regression analysis, differences in patient satisfaction between pedicle TRAM and DIEP flap reconstruction were no longer observed. Discussing satisfaction outcomes with patients will help them make educated decisions about breast reconstruction.

e13559Background: We observe the occurrence of multiple cancers in patients diagnosed with one cancer. Individuals with cancer are at increased risk for subsequent tumours. This risk is multi-facto...

To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague-Dawley rats to CIH or to room air sham (Sham) for 8 hours/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8 ± 15.6% of baseline; Sham 112.2 ± 10.0 % of baseline; CIH vs. Sham, P = 0.0373). This enhanced sympathetic response to i.c.v. ET-1 was associated with greater expression of endothelin receptor A (ETA) protein in the subfornical organs of CIH-exposed relative to Sham-exposed rats. We conclude that 3-week CIH exposure enhances central ET-1 receptor expression and the sympathetic response to i.c.v. ET-1 suggesting central endothelin may contribute to the sympathetic and hemodynamic response to cyclic intermittent hypoxia.

Objective To determine whether angiotensin-converting enzyme (ACE) inhibitors and other antihypertensives are associated with risk of pneumonia. Methods We conducted a nested case-control study of incident pneumonia in a subcohort of hypertensive adults insured by several large commercial plans throughout the United States. Individuals with pneumonia were matched on age, sex, region, and subscriber status with up to 10 controls free of pneumonia at the time of case diagnosis. We examined use of beta-blockers, calcium channel blockers, ACE inhibitors (lipophilic and hydrophilic), angiotensin receptor blockers, and thiazides in the prior 3 and 12 months. Results A total of 7429 cases of pneumonia occurred among 305 958 hypertensive individuals. Risk of pneumonia was higher among users of beta-blockers [adjusted odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.19], calcium channel blockers (adjusted OR 1.09, 95% CI 1.00-1.17), and lipophilic ACE inhibitors (adjusted OR 1.15, 95% CI 1.03-1.28) in the preceding 3 months; risks were also higher for use in the preceding 12 months. We observed lower risk with thiazide use in the preceding 3 months (adjusted OR 0.90, 95% CI 0.81-0.99) and hydrophilic ACE inhibitor use in the preceding year (adjusted OR 0.86, 95% CI 0.75-0.99). Conclusion In this population of middle-aged Americans with hypertension, we observed a modestly higher risk of pneumonia with use of beta-blockers, calcium channel blockers, and lipophilic ACE inhibitors. These results are consistent with possible differences in noncardiovascular outcomes among users of antihypertensives and other commonly used cardiovascular drugs but require confirmation in other populations.

To compare the capability of diffusion-weighted (DW) and contrast material-enhanced magnetic resonance (MR) imaging to provide diagnostic information on residual breast cancers following neoadjuvant chemotherapy and to assess apparent diffusion coefficients (ADCs) of the carcinoma prior to neoadjuvant chemotherapy to determine if the method could help predict response to chemotherapy.Institutional review board approval and informed consent were obtained. Three hundred ninety-eight patients underwent MR imaging of the breast, including DW MR (b values, 0 and 1500 sec/mm(2)) and contrast-enhanced MR imaging. Of these, the contralateral breast in 73 women was used as a control. Seventy-two patients with 73 lesions with malignant disease were treated by using neoadjuvant chemotherapy and were examined for residual disease following therapy. Three were excluded because of prolonged intervals between final MR imaging and surgery. Thus, 69 patients (70 lesions) with DW and contrast-enhanced MR imaging results were compared with postoperative histopathologic findings. The ADCs of the carcinoma prior to neoadjuvant chemotherapy were calculated for each patient, and those with complete response and residual disease were compared.The accuracy for depicting residual tumor was 96% for DW MR imaging, compared with an accuracy of 89% for contrast-enhanced MR imaging (P = .06). There was no significant difference in prechemotherapy ADCs between pathologic complete response cases and those with residual disease.DW MR imaging had at least as good of accuracy as did contrast-enhanced MR imaging for monitoring neoadjuvant chemotherapy. The ADCs prior to chemotherapy did not predict response to chemotherapy. The use of DW imaging to visualize residual breast cancer without the need for contrast medium could be advantageous in women with impaired renal function.

BACKGROUND: The duration of action of neuromuscular blocking drugs (NBDs) varies between individuals and even within individuals in different settings. OBJECTIVES: To define predictors of variance in duration of action of rocuronium and cisatracurium administered long-term. METHODS: A prospective, double-blind, multicenter trial that included 113 patients scheduled for major abdominal surgery and postoperative admission to the intensive care unit. Patients received repetitive (median, 7) equipotent doses of rocuronium or cisatracurium to maintain deep relaxation (twitch height of the adductor pollicis muscle

Although nerve conduction studies/electromyograms are often requested to evaluate hospitalized patients (inpatients) with suspected neuromuscular diseases, their clinical utility has not been studied. They can be technically challenging, especially in intensive care units. We studied the contribution of inpatient electromyograms (IP-EMGs) to the management of patients with suspected neuromuscular disorders. A total of 103 IP-EMGs in 98 patients were analyzed. IP-EMGs confirmed the clinical diagnosis in 53.3% and provided a new, clinically relevant diagnosis in 12.6%. IP-EMGs revealed only an incidental diagnosis in 14.5%, were inconclusive in 16.5%, and were normal in 3%. In over a quarter of patients, IP-EMGs assisted in planning further diagnostic evaluation or treatment. Although IP-EMGs most often only confirm already suspected diagnoses, in a substantial minority of patients they lead to the identification of clinically unsuspected, significant diagnoses that alter subsequent clinical care. Muscle Nerve 40: 195-199, 2009.

Development of new, microsurgical techniques for breast reconstruction has led to more natural and durable reconstruction while minimizing morbidity. Despite these advances, institutions are slow to integrate subspecialized programs because of the additional resources required. In February 2004, our institution developed a microsurgery program for perforator flap breast reconstruction. The purpose of this study is to analyze the impact of this program with attention to reconstruction rates, patient satisfaction, and referral patterns.A retrospective chart review was performed on all women who had undergone mastectomy or breast reconstruction at our hospital. A total of 1,172 patients were identified between 1999 and 2006. Patients who had breast reconstruction received a validated questionnaire on satisfaction, health-related quality of life, and sociodemographic data. A 75.4% response rate was obtained.Since the program's inception, there has been a significant increase in the immediate reconstruction rate from 51.5% to 63.9% (p0.001). Between the two time periods, general patient satisfaction after breast reconstruction increased from 58.5% to 74.4% (p0.001), and aesthetic satisfaction increased from 58.5% to 69.9% (p = 0.010). In addition, we have seen a 4.1-fold increase in the number of patients per year from outside institutions for delayed breast reconstruction.The addition of a perforator flap program for breast reconstruction to accredited cancer centers can increase both patient satisfaction and reconstruction rates. The shift in referral patterns emphasizes the role of breast reconstruction within a regional referral center.

We compared the effect of oxygen on the apnea-hypopnea index (AHI) in 6 obstructive sleep apnea patients with a relatively high loop gain (LG) and 6 with a low LG. LG is a measure of ventilatory control stability. In the high LG group (unstable ventilatory control system), oxygen reduced the LG from 0.69 ± 0.18 to 0.34 ± 0.04 (p < 0.001) and lowered the AHI by 53 ± 33 percent (p = 0.04 compared to the percent reduction in the low LG group). In the low LG group (stable ventilatory control system), oxygen had no effect on LG (0.24 ± 0.04 on room air, 0.29 ± 0.07 on oxygen, p = 0.73) and very little effect on AHI (8 ± 27 percent reduction with oxygen). These data suggest that ventilatory instability is an important mechanism causing obstructive sleep apnea in some patients (those with a relatively high LG), since lowering LG with oxygen in these patients significantly reduces AHI.

The prevalence of central apnoea and periodic breathing is increased in the elderly. This implies that the chemical control of breathing might become less stable with ageing. To investigate this, we measured loop gain in healthy elderly individuals using proportional assist ventilation. Loop gain is an engineering term that describes the stability of a system controlled by feedback loops, such as the respiratory control system. A loop gain close to zero indicates a stable system, whereas a loop gain close to or greater than one indicates an unstable system. Eleven healthy elderly subjects were studied with a mean +/- S.D. age and body mass index (BMI) of 71 +/- 5 years and 25 +/- 3 kg m(-2), respectively. We also studied a small group of elderly individuals with obstructive sleep apnoea (OSA) for comparison (n = 3, age 68 +/- 1 years, BMI 32 +/- 11 kg m(-2)). Comparisons were made with previously studied young individuals (age 27 +/- 4 years, BMI 23 +/- 1 kg m(-2)). We found significantly lower loop gains in the healthy elderly group (loop gain

AIM: To determine the association between age and outcome in a large multicenter cohort of out-of-hospital cardiac arrest patients.METHODS: Retrospective, observational, cohort study of out-of-hospital cardiac arrest from the CARES registry between 2006 and 2013. Age was categorized into 5-year intervals and the association between age group and outcomes (return of spontaneous circulation (ROSC), survival and good neurological outcome) was assessed in univariable and multivariable analysis. We performed a subgroup analysis in patients who had return of spontaneous circulation.RESULTS: A total of 101,968 people were included. The median age was 66 years (quartiles: 54, 78) and 39% were female. 31,236 (30.6%) of the included patients had sustained ROSC, 9761 (9.6%) survived to hospital discharge and 8058 (7.9%) survived with a good neurological outcome. The proportion of patients with ROSC was highest in those with age CONCLUSIONS: Advanced age is associated with outcomes in out-of-hospital cardiac arrest. We did not identify a specific age threshold beyond which the chance of a meaningful recovery was excluded.

To study the association between periodontal disease (PD) and age-related macular degeneration (AMD).For this cross-sectional analysis, 8,208 adults aged 40 years or older with retinal photographs graded for AMD were used from the National Health and Nutrition Examination Survey III. National Health and Nutrition Examination Survey III standardized dental measurements of PD status (defined as loss of3 mm of attachment between the gum and tooth in at least 10% of sites measured). Participants were stratified into 60 years or younger and older than 60 years of age groups. Association between PD and AMD was assessed while controlling for sex, race, education, poverty income ratio, smoking, hypertension, body mass index, cardiovascular disease, and C-reactive protein.In this population, a total of 52.30% had PD, and the prevalence of AMD was 11.45%. Logistic regression model controlled for confounders and stratified by age 60 years or younger versus older than 60 years showed PD to be independently associated with an increased risk for AMD (odds ratio = 1.96, 95% confidence interval = 1.22-3.14, P = 0.006) for those aged 60 years or younger but not for subjects older than 60 years (odds ratio = 1.32, confidence interval = 0.93-1.90, P = 0.120).In this population-based study, PD is independently associated with AMD in those aged 60 years or younger.

Background: Developing medical prediction models remains time and labor consuming. We propose the approach where information collected from published epidemiological outcome studies is quickly converted into prediction models. Methods: We used general expressions for regression models to derive prediction formulae defining the probability of the outcome and relative risk indicator. Risk indicator (R) is calculated as a linear combination of predictors multiplied by regression coefficients and then is placed on the scale of 0 to 10 for interpretability. Prediction expression for the probability (P) of the outcome is derived from general expression for logistic regression and proportional hazard models. The intercept is calculated based upon the outcome rate in the population and the risk indicator assigned to a subject representing mean characteristics of the population (E’). We also consider linear expression where probability of outcome is the product of risk indicator and the ratio of observed outcome rate and E’. Results: These models were explored and compared in a numeric simulation exercise and also using real data obtained from NHANES dataset. All three expressions generate very similar predictions in the lower categories of risk indicator. In the groups with the higher value of risk indicator linear expression tends to predict lower probability than exponential expressions and also lower than observed. Conclusions: We demonstrated simple technique (named Woodpecker™) that might allow deriving functional prediction model and risk stratification tool from the report of clinical outcome study using multivariate regression model.

Purpose To evaluate the capability of coronal reformations of chest on 64-row MDCT in demonstrating thoracic abnormalities in comparison with axial images. Materials and methods Thirty-eight consecutive patients who underwent pulmonary CTA on 64-row MDCT were retrospectively studied with institutional review board (IRB) approval. Contiguous 2 mm axial and coronal images were reviewed independently with a 1-week interval, by consensus reading of two board-certified radiologists. Overall image quality was graded using a five-point scale. Abnormalities in mediastinum, hilum, pulmonary vessels, aorta, heart, esophagus, pleura, chest wall, and lung parenchyma were scored: 1 = definitely absent, 2 = probably absent, 3 = equivocal, 4 = probably present, 5 = definitely present. Scores on axial and coronal images were compared using weighted κ analysis. Results Overall image quality was not different with statistical relevance between axial and coronal images (mean/median scores; 3.7/4; 3.6/4, respectively, P = 0.286, Wilcoxon signed-rank test). Significant agreement was observed between axial and coronal scores (mean weighted κ , 0.661; range, 0.362–1). Agreement was almost perfect for pneumothorax, lung and pleural mass, effusion and consolidation (weighted κ = 0.833–1); substantial for pulmonary embolism, trachea, mediastinal lymphadenopathy and non-skeletal chest wall lesion, heart, esophagus, and emphysema (weighted κ , 0.618–0.799); moderate for atelectasis, mediastinum, hilar nodes, aorta, other lung lesions, skeletal chest wall lesions, linear scarring, nodules >1 cm, pulmonary artery abnormalities and pleural thickening (weighted κ , 0.405–0.592); and fair for nodules κ = 0.362). Conclusion Coronal reformations on 64-row MDCT had substantial agreement with axial images for evaluation of the majority of thoracic abnormalities.

Objective: To assess kidney function via creatinine clearance before and after radiotherapy in gynecologic cancer patients treated to the para-aortic (PA) area via Intensity Modulated Radiotherapy (IMRT). Methods: Twenty-three patients underwent IMRT to the para-aortic area, were followed for at least 5 months, and had the necessary laboratory data to calculate creatinine clearance. Various patient-related factors and radiotherapy-treatment related factors were analyzed to determine their association with changes in CrCl. Results: Median follow-up was 10.9 months (range, 5-19 months). Median patient age was 51.7 years (range, 22-78). The average initial CrCl was noted to be 109.23 mL/min (range, 38.64-188.38) before radiotherapy and decreased to 90.00 mL/min (29.31-175.61) after radiotherapy (P = 0.004). Although 17 patients had a decrease in their CrCl, 6 were found to have a slight elevation. Five factors were associated with a decrement in CrCl greater than the average decrease (17.6%): presence of hydronephrosis, age

Objective: To evaluate coronal reformations of the chest on 64-row multidetector-row computed tomography (MDCT) for detection of pulmonary embolisms compared with axial images. Methods: Thirty-eight consecutive patients who underwent pulmonary computed tomography angiography (CTA) on 64-row MDCT for a suspected pulmonary embolism were retrospectively studied. Contiguous 2-mm axial and coronal images were reviewed independently. A pulmonary embolism was assessed in the main, lobar, or segmental pulmonary arteries and was scored using a 5-point scale. Results: A pulmonary embolism was demonstrated in 10% (4 of 38) of axial images and 16% (6 of 38) of coronal images. Interpretation was concordant in 95% to 100% of cases for a main or lobar pulmonary embolism and in 80% to 82% of cases for a segmental pulmonary embolism. Agreement of scores was almost perfect for a amain or lobar pulmonary embolism (mean weighted κ value = 0.969) and moderate to good for a segmental pulmonary embolism (mean weighted κ value = 0.560). Conclusion: Coronal reformations of the chest on 64-row MDCT were as informative as axial images for the detection of main, lobar, and segmental pulmonary embolisms.

Two members of the MTG/ETO family of transcriptional corepressors, MTG8 and MTG16, are disrupted by chromosomal translocations in up to 15% of acute myeloid leukemia cases. The third family member, MTGR1, was identified as a factor that associates with the t(8;21) fusion protein RUNX1-MTG8. We demonstrate that Mtgr1 associates with mSin3A, N-CoR, and histone deacetylase 3 and that when tethered to DNA, Mtgr1 represses transcription, suggesting that Mtgr1 also acts as a transcriptional corepressor. To define the biological function of Mtgr1, we created Mtgr1-null mice. These mice are proportionally smaller than their littermates during embryogenesis and throughout their life span but otherwise develop normally. However, these mice display a progressive reduction in the secretory epithelial cell lineage in the small intestine. This is not due to the loss of small intestinal progenitor cells expressing Gfi1, which is required for the formation of goblet and Paneth cells, implying that loss of Mtgr1 impairs the maturation of secretory cells in the small intestine.

The Women's Health Study of Accra is a cross-sectional study designed to measure the burden of communicable and noncommunicable diseases in adult women residing in Accra, Ghana. This study assessed the prevalence rate of HIV and risk factors associated with HIV infection in 1,328 women age 18 years and older. The weighted overall HIV prevalence rate for women residing in Accra is 3.1%. The highest prevalence rate of HIV infections was identified in women age 25 to 29 years at 8.3%, OR (95%CI) 3.8 (1.68-8.33), P = 001. In addition to young age, other significant risk factors included sexually transmitted infection (STI) symptoms (OR 1.81 [1.14-2.87], P = 0.012) and mean number of lifetime sexual partners (P < 0.001). All HIV-positive women were sexually active. Other findings significantly associated with HIV-positive status included chills, oral lesions, tuberculosis, bloody sputum production, and intestinal parasite infections. There was a significant association with HIV-positive status and locality of residence in the city. There was no association with reported use of condoms, blood transfusions, surgery, reproductive health history including pregnancy or number of sexual partners, symptoms suggestive of AIDS, or self-perception of health. There was also no association with education level, religion, ethnicity, marital status, or socioeconomic level. This community-based study confirms the need to target young, sexually active women for HIV educational and preventive initiatives. A strong Ghanaian public health initiative to increase awareness of the risks of HIV and the link to STIs is critical at this time to prevent the further increase in HIV prevalence and the resultant HIV-associated illnesses.

Background: Group B streptococcal infections remain an important cause of morbidity and mortality in newborns. Methods: Neonatal group B streptococcal cases were identified by active surveillance in 4 urban Tennessee counties. Medical records of mothers of cases and a sample of other pregnant women with live births from the same population were reviewed to determine whether the screening or risk-based approach was used for prevention of early onset group B streptococcal disease and to assess other factors affecting preventability of cases. Results: During 1998 and 1999, 43% of women underwent prenatal group B streptococcal screening. County of residence was the only factor independently associated with not being screened [odds ratio, 7.85; 95% confidence interval (4.69, 13.16)]. Ten affected babies were born to screened mothers (0.40 per 1000). In 9 of these 10, problems were identified: mothers had positive screening cultures but did not receive optimal intrapartum antibiotics (n = 3 of 4); mothers had negative screening cultures (n = 4); and mothers were screened, but the results were unknown, and intrapartum antibiotics were not given (n = 2). Conclusions: Challenges to implementation of group B streptococcal screening and prophylaxis include insufficient screening, suboptimal intrapartum antibiotics, disease despite negative screening cultures and timely communication of screening results at delivery. An awareness of such problems may lead to supplemental measures to further reduce group B streptococcal disease.

The transforming growth factor beta (TGF-beta) signaling pathway, which is activated by the TGF-beta receptor complex consisting of type I and type II TGF-beta receptors (TGFBR1 and TGFBR2), regulates cell growth and death. TGF-beta and components of its signaling pathway, particularly TGFBR2, have been implicated as tumor suppressor genes and important antimitogenic factors in the gastrointestinal tract and liver. An in vivo approach to study these effects has been hindered by the embryonic lethality of Tgfbr2(-/-) mice and poor viability of the Tgfb1(-/-) mice. Consequently, we have developed a hepatocyte-specific Tgfbr2 knockout mouse, the Alb-cre Tgfbr2(flx/flx) mouse, to study the physiologically relevant effects of TGF-beta signaling on epithelial cell proliferation in vivo. After 70% hepatectomy, we observed increased proliferation and an increased liver mass : body weight ratio in the Alb-cre Tgfbr2(flx/flx) mice compared to Tgfbr2(flx/flx) mice. We also observed decreased expression and increased phosphorylation of p130 in the livers from the Alb-cre Tgfbr2(flx/flx) mice as well as increased expression of cyclin E, which is transcriptionally regulated, in part, by p130:E2F4. Consistent with these results, in a hepatocyte cell line derived from the Tgfbr2(flx/flx) mice, we found that TGF-beta increases the nuclear localization of E2F4, and presumably the transcriptional repression of the p130:E2F4 complex. Thus, we have demonstrated that TGF-beta signaling in vivo regulates the mitogenic response in the regenerating liver, affecting the liver mass : body weight ratio after partial hepatectomy, and that these mitogenic responses are accompanied by alterations in p130 expression and phosphorylation, implicating p130 as one of the proteins regulated in vivo by TGF-beta during liver regeneration.

Colon cancer is the third leading cause of cancer-related death in the United States, affecting ∼147,000 people each year. Most colon cancers arise from benign neoplasms and evolve into adenocarcinomas through a stepwise histologic progression sequence that starts from adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations and, more recently, epigenetic alterations have been associated with specific steps in this polyp-adenocarcinoma sequence and likely drive the histologic progression of colon cancer. Consequently, we have assessed in colon adenomas and hyperplastic polyps the methylation status of MGMT, CDKN2A, and MLH1 to determine the timing and frequency of these events in the polyp-carcinoma progression sequence and subsequently to analyze the potential for these methylated genes to be molecular markers for adenomas and hyperplastic polyps. We have found that methylated MGMT, CDKN2A, and MLH1 occur in 49%, 34%, and 7% of adenomas and in 5%, 10%, and 7% of hyperplastic polyps, respectively, and that they are more common in histologically advanced adenomas. Furthermore, analysis of fecal DNA from persons who have undergone colonoscopic exams revealed methylated CDKN2A, MGMT, and MLH1 in fecal DNA from 31%, 48%, and 0% of individuals with adenomas and from 16%, 27%, and 10% of individuals with no detectable polyps, respectively. These results show that aberrant methylated genes can be detected frequently in sporadic colon polyps and that they can be detected in fecal DNA. Notably, improvements in the specificity and sensitivity of the fecal DNA-based assays will be needed to make them clinically useful diagnostic tests for polyps.

Deregulation of members of the transforming growth factor (TGF)-β signaling pathway occurs often in colon cancers and is believed to affect the formation of primary colon cancer. Mutational inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway and occurs in ∼20–30% of all colon cancers. By mating Fabpl4xat-132 Cre mice with Tgfbr2flx/flx mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-β signaling in vivo on colon cancer formation induced by azoxymethane (AOM). We have observed a significant increase in the number of AOM-induced adenomas and adenocarcinomas in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice compared with Tgfbr2flx/flx mice, which have intact TGF-β receptor type II (TGFBR2) in the colon epithelium, and we have found increased proliferation in the neoplasms occurring in the Fabpl4xat-132 Cre Tgfbr2flx/flx mice. These results implicate the loss of TGF-β-mediated growth inhibition as one of the in vivo mechanisms through which TGFBR2 inactivation contributes to colon cancer formation. Thus, we have demonstrated that loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms, providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor gene in the colon.

Objective To examine core body temperature, energy expenditure, and respiratory quotient among breast cancer survivors experiencing hot flashes and compare these data to published studies from healthy women. Design In an observational study, nine breast cancer survivors with daily hot flashes who met specified criteria spent 24 hours in a temperature- and humidity-controlled whole-room indirect calorimeter (ie, metabolic room). Demographic and disease/treatment information were obtained and the following were measured: hot flashes via sternal skin conductance monitoring (sampled every second); core body temperature via an ingested radiotelemetry pill (sampled every 10 seconds); and energy expenditure and respiratory quotient via a whole-room indirect calorimeter (calculated every minute). Results Circadian analysis of core temperature indicated wide variability with disrupted circadian rhythm noted in all women. Core temperature began to rise 20 minutes pre-flash to 7 minutes pre-flash (0.09 degrees C increase). Increases in energy expenditure and respiratory quotient increased with each hot flash. Conclusions Findings are comparable to published data from healthy women and warrant replication in larger, more diverse samples of women treated for breast cancer.

The present study describes the in vivo detection and imaging of tumour-associated MMP-7 (matrix metalloproteinase-7 or matrilysin) activity using a novel polymer-based fluorogenic substrate PB-M7VIS, which serves as a selective 'proteolytic beacon' (PB) for this metalloproteinase. PB-M7VIS is built on a PAMAM (polyamido amino) dendrimer core of 14.2 kDa, covalently coupled with an Fl (fluorescein)-labelled peptide Fl(AHX)RPLALWRS(AHX)C (where AHX stands for aminohexanoic acid) and with TMR (tetramethylrhodamine). PB-M7VIS is efficiently and selectively cleaved by MMP-7 with a k (cat)/ K (m) value of 1.9x10(5) M(-1).s(-1) as measured by the rate of increase in Fl fluorescence (up to 17-fold for the cleavage of an optimized PB-M7VIS) with minimal change in the TMR fluorescence. The K (m) value for PB-M7VIS is approx. 0.5 microM, which is approx. two orders of magnitude lower when compared with that for an analogous soluble peptide, indicating efficient interaction of MMP-7 with the synthetic polymeric substrate. With MMP-2 or -3, the k (cat)/ K (m) value for PB-M7VIS is approx. 56- or 13-fold lower respectively, when compared with MMP-7. In PB-M7VIS, Fl(AHX)RPLALWRS(AHX)C is a selective optical sensor of MMP-7 activity and TMR serves to detect both the uncleaved and cleaved reagents. Each of these can be visualized as subcutaneous fluorescent phantoms in a mouse and optically discriminated based on the ratio of green/red (Fl/TMR) fluorescence. The in vivo specificity of PB-M7VIS was tested in a mouse xenograft model. Intravenous administration of PB-M7VIS gave significantly enhanced Fl fluorescence from MMP-7-positive tumours, but not from control tumours ( P

2×K contingency tables having both ordinal and nominal categories are often encountered in various types of studies. Such data are referred to as ‘mixed’ categorical data in this article. To apply a method for ordered categorical data one has to discard the nominal categories, and to apply a method for nominal categories one has to discard the ordering information inherent in the ordered categories. Therefore, investigators often either discard observations in nominal categories or discard the ordering of the categories before analysing such data. Some information will be lost in both approaches. A method for analysing data in 2×K ‘mixed’ tables is proposed in this paper which can be considered as an extension of well known methods for nominal and ordered categories. The proposed method utilizes observations in the nominal categories as well as the ordering information. If all the categories were ordered then the proposed method reduces to the trend test, and if all the categories were nominal then the proposed method reduced to Pearson's chi-square test. Copyright © 2002 John Wiley & Sons, Ltd.

Background Many lung transplant programs employ lengthy regimens of IV ganciclovir therapy to prevent disease due to cytomegalovirus (CMV). In 1994, we introduced a regimen of delayed ganciclovir prophylaxis for CMV infection. This consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after transplantation, with subsequent viral monitoring and preemptive therapy as needed. When not receiving ganciclovir, patients received oral acyclovir, 800 mg tid, for 6 months. CMV-seronegative patients with seropositive donors also received four doses of CMV hyperimmune globulin. This study analyzes the CMV outcomes of 54 patients who received the delayed regimen compared to 33 historical control subjects who received only acyclovir prophylaxis (n = 28) or oral acyclovir and 2 to 4 weeks of ganciclovir early after transplantation (n = 5). Methods CMV detection was by shell vial culture or IgG seroconversion; after 1996, CMV detection was by blood antigenemia. The diagnosis of CMV disease also required a typical clinical syndrome or pathologic evidence of CMV. The main outcome was the actuarial incidence of CMV infection and disease. In order to account for the effect of other important risk factors for CMV infection, the time to CMV infection and disease was also studied as dependant variables in a Cox proportional-hazard analysis, with the delayed regimen and other important risk factors as independent variables. Results The delayed regimen reduced the actuarial incidence of CMV infection from 80 to 48% (p Conclusion A regimen of CMV prophylaxis employing 2 weeks of IV ganciclovir initiated 3 to 4 weeks after lung transplantation followed by virologic monitoring and preemptive therapy as needed provides good protection against CMV disease.

The diagnostic accuracy of the rectal swab (RS) culture method in identifying gastrointestinal colonization with vancomycin-resistant enterococci (VRE) is not known. Serial quantitative stool cultures, skin cultures, and RS cultures were performed for patients with VRE infections to assess the false-negative rate of the RS and the prevalence of skin colonization, a prerequisite for cross-transmission, at varying VRE stool densities. A total of 35 stool samples were obtained from 13 patients. The sensitivity of the RS culture was 58%; it ranged from 100%, at VRE densities of > or =7.5 log10 colony forming units (cfu) per gram of stool, to 0%, at densities of < or =4.5 log10 cfu per gram of stool. Skin colonization was detected at these low VRE stool densities, but it was more common at higher VRE densities (P

Dexamethasone is often used to counteract rapid neurologic deterioration in patients with recurrent glioblastoma. We therefore asked whether dexamethasone reduces the efficacy of treatments. The phase III trial comparing tumor-treating alternating electric fields (TTFields) to active chemotherapy offered us a unique opportunity to address this question that was unencumbered by the confounding immune and hematologic side effects of chemotherapy. Using an unsupervised binary partitioning algorithm, we segregated subjects in the trial based on the dexamethasone dose that yielded the greatest overall survival (OS) difference. The median OS of TTFields-treated subjects who used ≤4.1 mg/day of dexamethasone was 11.0 (95% confidence interval [CI] 8.8-16.6) months compared to 4.8 (95%CI 3.9-6.0) months in those who used >4.1 mg of dexamethasone (χ2 = 34.6, P < 0.0001). Subjects who were treated with chemotherapy also benefited from the same lower dose of dexamethasone, median OS 8.9 (95%CI 7.2-16.1) months with ≤4.1 mg/day versus 6.0 (95%CI 3.5-8.3) months with >4.1 mg/day (χ2 = 10.0, P < 0.0015). The same dexamethasone cutoff was validated in a single-institutional cohort with a Karnofsky performance score of ≥70 and treated with either TTFields monotherapy or in combination with bevacizumab. The median OS of patients who used dexamethasone ≤4.1 mg/day was 8.7 (95%CI 6.7-not available [NA]) months compared to those who used >4.1 mg/day was 3.2 (95%CI 1.2-NA) months (χ2 = 11.1, P = 0.0009). A 3-dimensional binary partitioning analysis revealed that the best outcome was from a group of patients with CD4 >144 cells/mm3, CD4/CD8 ≤1.1, dexamethasone ≤0.6 mg/day and their median OS was 13.7 (95%CI 10.8-13.8) months as compared to the rest with a median OS of 4.6 months (95%CI 0.3-22.7). Dexamethasone exerts a profound effect on both TTFields and chemotherapy treatment efficacy in patients with recurrent glioblastoma. Our data strongly suggest that dexamethasone can cause global immunosuppression and this most likely interferes with immune effector function against the tumor.

We sought to perform a patient-level meta-analysis using the individual patient data of the trials identified in our previous study-level meta-analysis investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on blood pressure (BP).Patient-level meta-analysis.N/A.968 adult OSA subjects without major comorbidities drawn from eight randomized controlled trials.Therapeutic PAP versus non-therapeutic control conditions (sham-PAP, pill placebo or standard care) over at least one week.The mean reductions in BP between PAP and non-therapeutic control arms were -2.27 mm Hg (95% CI -4.01 to -0.54) for systolic BP and -1.78 mm Hg (95% CI -2.99 to -0.58) for diastolic BP. The presence of uncontrolled hypertension at baseline was significantly associated with a reduction in systolic BP of 7.1 mm Hg and diastolic BP of 4.3 mm Hg after controlling for OSA severity (apnea-hypopnea index, Epworth Sleepiness Scale score, PAP level), patient demographics (age, gender, body mass index, use of antihypertensive medication/s), and measures of PAP efficacy (PAP adherence and treatment duration).OSA patients with uncontrolled hypertension are likely to gain the largest benefit from PAP in terms of a substantial reduction in BP, even after controlling for disease severity.

To develop and validate an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation.Prospective cohort study.The adult medical and coronary intensive care units of a tertiary care, university-based medical center.Thirty-eight patients admitted to the intensive care units.We designed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU. Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference standard, a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders (fourth edition). A total of 293 daily, paired evaluations were completed, with reference standard diagnoses of delirium in 42% and coma in 27% of all observations. To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days, we used only the first-alert or lethargic comparison evaluation in each patient. Thirty-three of 38 patients (87%) developed delirium during their intensive care unit stay, mean duration of 4.2 +/- 1.7 days. Excluding evaluations of comatose patients because of lack of characteristic delirium features, the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84, 0.79, and 0.95, respectively (p.001). The two nurses' and intensivist's sensitivities when using the CAM-ICU compared with the reference standard were 95%, 96%, and 100%, respectively, whereas their specificities were 93%, 93%, and 89%, respectively.The CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients. The CAM-ICU may be a useful instrument for both clinical and research purposes to monitor delirium in this challenging patient population.

We evaluated the relationship between the ratio of free-to-total prostate specific antigen (PSA) and prostate pathology, including grade, stage and tumor volume, among patients with prostate cancer who underwent radical prostatectomy.We prospectively analyzed 54 consecutive patients with prostate cancer who underwent radical prostatectomy and in whom frozen serum was available for assessment of free-to-total PSA ratio. Pathological review was done with whole mount sections, and total tumor volume was determined by planimetry. Comparison between free-to-total PSA ratio and pathological parameters was performed using the Pearson correlation coefficient.Among the 54 patients mean total and free-to-total PSA ratio were 5.81 and 14.2 ng./ml., respectively, and free-to-total PSA ratio directly correlated with prostate volume (p = 0.037), and inversely correlated with Gleason score (p = 0.012) and extracapsular disease (p = 0.0074). Furthermore, there was a significant relationship between free-to-total PSA ratio and pathological stage pT2a/b in 39 cases versus pT3a/b in 15 (p = 0.005). Overall, there was no correlation between free-to-total PSA ratio and tumor volume. However, among 37 patients with an increased PSA, defined as greater than 4.0 ng./ml., a significant inverse relationship between free-to-total PSA ratio and tumor volume was identified (p = 0.01). Among this subset there was only a weak correlation with prostate volume (p = 0.049).Our findings suggest that free-to-total PSA ratio may be predictive of tumor biology among those patients with a total PSA of greater than 4 ng./ml. as evidenced by good correlation with tumor grade and volume. This finding appears to be independent of prostate volume. These preliminary results suggest the need for additional studies among patients with an increased PSA designed to evaluate the potential role of free-to-total PSA ratio in combination with traditional clinical variables in the prediction of prostate cancer pathology.

We performed a prospective study based on the hypothesis that physiologic differences exist between men and women in strength after adjustments for body weight; that the size of the anterior cruciate ligament is proportionate to the strength of its antagonists, the quadriceps muscles; and that women have a relatively small anterior cruciate ligament, thus predisposing them to a disproportionate number of anterior cruciate ligament injuries. One hundred matched high school basketball players, 50 male and 50 female, were evaluated with anthropometric measurements, body fat analysis, muscle strength evaluation, and magnetic resonance imaging measurements of the intercondylar notch and cross-sectional area of the anterior cruciate ligament at the outlet. The male players were taller and heavier than their female counterparts, although they had 11% less body fat. Male players had statistically greater quadriceps and hamstring muscle strength than female players, even when adjustments were made for body weight. With adjustments for body weight, the size of the anterior cruciate ligament in girls was found to be statistically smaller than in boys. There was no statistically significant difference in the notch width index between the sexes. The study data support our hypothesis that sex differences in anterior cruciate ligament tear rates are caused primarily by several interrelated intrinsic factors. Most importantly, stiffness and muscular strength increase stress on the anterior cruciate ligament in female athletes. The anterior cruciate ligament, when adjustments have been made for body weight, is smaller in female athletes, and therefore, probably does not compensate for the lack of stiffness and strength.

For 2 × k contingency tables, we consider the statistic r*, the maximal correlation between the row and column variables, where the maximum is taken over all possible sets of scores (or “scales” or “weights”) assigned to the k categories. For general m × k contingency tables, methods involving the maximization over sets of scores assigned to the categories (called dual-scaling methods) have been criticized for lack of statistical interpretation and for difficulty of computation. For the case m = 2, however, where nominal categorical data on two populations are compared, this article shows that r* has meaningful interpretations as a multiple correlation coefficient, as a numerical measure of association, and as an upper bound on correlation for reduced tables. These interpretations lead to a better understanding of the nature of the association between the two variables. These interpretations also yield insight into the role of the usual chi-square statistic for 2 × k tables. Furthermore, both r* ...

Restricting sleep on week days and catching up on sleep on weekend days is a highly prevalent pattern in work and school populations. We hypothesized that the repeated exposure to such patterns progressively increases the inflammatory response, due to reduced GC sensitivity of monocytes. Fourteen participants (age 25 ± 1 yrs) completed two 25-day-in-hospital periods; sleep-restriction and control-sleep in randomized order. The sleep-restriction condition consisted of three weekly cycles of 5 days with 4 h of sleep/night followed by 2 days with 8 h of sleep/night. Blood draws were taken at 11:30 h on the baseline day and the end of each sleep-restriction and recovery-sleep period. The inflammatory response was assessed by interleukin (IL)-6 positive monocytes (determined by flow cytometry); GC sensitivity of monocytes was determined by measuring the ability of dexamethasone to suppress lipopolysaccharide-stimulated IL-6 expression. IL-6 positive monocytes increased in the second and third week of sleep-restriction over control-sleep by 15% and 20%, respectively (both p 0.05), and did not return to baseline levels during intermittent recovery-sleep. GC sensitivity of monocytes was increased across all 3 weeks of sleep-restriction when compared to control-sleep, and did not normalize during intermittent recovery-sleep periods (all p 0.05). In conclusion, despite an increase in the sensitivity of monocytes to the counter-inflammatory GC signal, monocytes still express more IL-6 in response to repeated exposure of sleep-restriction. Importantly, recovery-sleep does not normalize these changes.

Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA.This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels.Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = -0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002).Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted.

Background: Modern immunosuppression and rabbit antithymocyte globulin (rATG) have facilitated the success of early steroid withdrawal (ESW) protocols. Little data exist on optimal rATG dosing in ESW protocols. Methods: Rejection at 12 months in era 1 (four doses of rATG, 1.25 mg/kg) vs. era 2 (three doses of rATG, 1.25 mg/kg) was the primary endpoint. Secondary endpoints included patient and graft survival, renal function and infectious complications. Factors associated with rejection at 1 year were identified. Results: 199 patients received rATG induction and ESW: 102 in era 1 and 97 in era 2. Compared to era 1, era 2 was not associated with worse outcomes, including rejection, renal function, infection or graft survival. Rejection at 1 year and uncensored graft survival differed between the dosing groups. Rejection rates were significantly higher in the Conclusions: A comparison of rATG dosing based on era did not result in a significant difference in rejection, renal function, infection or graft survival. However, when evaluating the study population based on actual dose received there were notable differences in both rejection rates and uncensored graft survival.