Novel artificial neural network for early detection of prostate cancer.

PURPOSE: Two artificial neural networks (ANN) for the early detection of prostate cancer in men with total prostate-specific antigen (PSA) levels from 2.5 to 4 ng/mL and from 4 to 10 ng/mL were prospectively developed. The predictive accuracy of the ANN was compared with that obtained by use of conventional statistical analysis of standard PSA parameters. PATIENTS AND METHODS: Consecutive men with a serum total PSA level between 4 and 10 ng/mL (n = 974) and between 2.5 and 4 ng/mL (n = 272) were analyzed. A separate ANN model was developed for each group of patients. Analyses were performed to determine the presence of prostate cancer. RESULTS: The area under the receiver operator characteristic (ROC) curve (AUC) was 87.6% and 91.3% for the 2.5 to 4 ng/mL and 4 to 10 ng/mL ANN models, respectively. For the latter model, the AUC generated by the ANN was significantly higher than that produced by the single variables of total PSA, percentage of free PSA, PSA density of the transition zone (TZ), and TZ volume (P <.01), but not significantly higher compared with multivariate analysis. For the 2.5 to 4 ng/mL model, the AUC of the ANN ROC curve was significantly higher than the AUCs for percentage of free PSA (P =.0239), PSA-TZ (P =.0204), and PSA density and total prostate volume (P <.01 for both). CONCLUSION: The predictive accuracy of the ANN was superior to that of conventional PSA parameters. ANN models might change the way patients referred for early prostate cancer detection are counseled regarding the need for prostate biopsy.     

疟原虫组织期裂殖体杀灭剂的研究:2-取代苄氧基(或甲氧基)-5-取代苯氧基-伯氨喹类似物的合成

本文报道了间日疟根治药伯氮喹2位引入取代苄氧基或甲氧基,5位引入取代苯氧基的类似物的合成。其中以化合物39及45对疟原虫组织期裂殖体的作用最强,约氏疟原虫子孢子感染的小鼠喂服100mg/kg单剂,分别有80%及90%的受试小鼠未查见原虫血症。化合物45降至20mg/kg单剂时,80%的受试小鼠也未出现原虫;对小鼠的急性毒性低于伯氨喹。     

Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components

OBJECTIVE: To reduce the incidence of transfusion-related acute lung injury (ALI), the American Association of Blood Banks recently recommended rapid implementation of strategies to minimize transfusion of high plasma volume components, fresh frozen plasma and apheresis platelets, from potentially alloimmunized donors, especially females. The objective of this study was to evaluate the effect of transfusing components from male-only vs. female donors on development of ALI, gas exchange, and outcome in critically ill patients. DESIGN: In this retrospective case-control study, we identified patients who received high plasma volume components from male-only donors and compared them with patients matched by severity of illness, postoperative state, and number of transfusions but who received high plasma volume components from female donors. SETTING: Four intensive care units at a tertiary medical center. PATIENTS: Critically ill patients who received >2 units of fresh frozen plasma or apheresis platelets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a database of 3,567 patients who received a total of 46,101 units of fresh frozen plasma and 6,251 units of apheresis platelets, we identified 112 patients who received three or more male-only donor components and 112 matched controls. Baseline characteristics, ALI risk factors, and development of ALI were similar between the two groups. Arterial oxygenation (PaO2/FIO2) worsened after the female (mean difference -52, 95% confidence interval -14 to -91, p = .008) but not after male-only donor product transfusion (mean difference 22, 95% confidence interval -23 to 67, p = .325). Male-only component recipients had more ventilator-free days (median 28 vs. 27, p = .006) and a trend toward lower hospital mortality rates (14% vs. 24%, p = .054). CONCLUSIONS: In critically ill recipients of high plasma volume components, gas exchange worsened significantly after transfusion of female but not male donor components. Prospective studies are needed to evaluate the effect of recommendations by the American Association of Blood Banks on outcome of transfused critically ill patients.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Effect of transvenous cardiac resynchronization therapy device implantation on cardiac troponin I release

BACKGROUND: Pacemaker and implantable cardioverter defibrillator (ICD) implantation increases cardiac troponin I (cTnI) levels which indicates myocardial injury. During implantation of a cardiac resynchronization therapy (CRT) device, balloon inflation for coronary sinus (CS) venogram, cannulation of CS side branch, and electrode advancement may interfere with CS drainage and, hence, may decrease the washout of toxic metabolites from the heart. Thus, CRT implantation may further increase cTnI levels. In this study, we investigated the effects of CRT implantation on cTnI release. METHODS: We included 10 patients (mean age = 57 +/- 15 years) in whom a successful transvenous CRT system was implanted (CRT group). Twenty patients (mean age = 65 +/- 10 years) who underwent a transvenous pacemaker or ICD implantation were included as the control group. Blood samples for cTnI were drawn at baseline and at six, 12, 18, and 24 hours thereafter. RESULTS: Baseline median cTnI levels were similar in CRT and control groups (0.03 ng/mL vs 0.02 ng/mL, respectively; P = 0.1). Postoperative cTnI levels during 24 hours were significantly higher in the CRT group (P < 0.05) by two-way repeated measures of analysis of variance. Post hoc analysis revealed that cTnI levels were higher at the 6th, 12th, 18th, and 24th hours compared to baseline levels (P < 0.001, P < 0.001, P < 0.01, and P < 0.01, respectively). There was a significant difference in the area under the curves (AUCs) of cTnI measurements (1.79 hr.ng/mL in the CRT group and 0.78 hr.ng/mL in the control group, P < 0.05). CONCLUSION: Postoperative cTnI levels were higher after CRT implantation than simple pacemaker/ICD implantation. This may be due to CS manipulation during CRT implantation.     

Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion

OBJECTIVE: We evaluated the effect of two quality improvement interventions (low tidal volume ventilation and restrictive transfusion) on the development of acute lung injury in mechanically ventilated patients. DESIGN: Observational cohort study. SETTING: Three intensive care units in a tertiary academic center. PATIENTS: We included patients who were mechanically ventilated for > or =48 hrs excluding those who refused research authorization or had preexisting acute lung injury or pneumonectomy. INTERVENTIONS: Multifaceted interdisciplinary intervention consisting of Web-based teaching, respiratory therapy protocol, and decision support within computerized order entry. MEASUREMENTS AND MAIN RESULTS: Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated before and 163 after the interventions. Baseline characteristics were similar between the two groups except for a lower frequency of sepsis (27% vs. 17%, p = .030), trend toward lower median glucose level (140 mg/dL, interquartile range 118-168 vs. 132 mg/dL, interquartile range 113-156, p = .096), and lower frequency of pneumonia (27% vs. 20%, p = .130) during the second period. We observed a large decrease in tidal volume (10.6-7.7 mL/kg predicted body weight, p < .001), in peak airway pressure (31-25 cm H2O, p < .001), and in the percentage of transfused patients (63% to 38%, p < .001) after the intervention. The frequency of acute lung injury decreased from 28% to 10% (p < .001). The duration of mechanical ventilation decreased from a median of 5 (interquartile range 4-9) to 4 (interquartile range 4-8) days (p = .030). When adjusted for baseline characteristics in a multivariate logistic regression analysis, protocol intervention was associated with a reduction in the frequency of new acute lung injury (odds ratio 0.21, 95% confidence interval 0.10-0.40). CONCLUSIONS: Interdisciplinary intervention effectively decreased large tidal volumes and unnecessary transfusion in mechanically ventilated patients and was associated with a decreased frequency of new acute lung injury.     

The effects of atorvastatin treatment on the fibrinolytic system in dyslipidemic patients

Statins have pleiotrophic effects related to the pathogenesis of atherosclerosis and thrombogenicity of the vessel wall beyond lipid lowering. The aim of the present study was to examine the effect of atorvastatin treatment on the fibrinolytic system in patients with dyslipidemia. The investigation was carried out on 41 dyslipidemic patients (21 males and 20 females) with a mean age of 53.8 years (range, 30-76). The patients were divided into subgroups according to their cholesterol and triglyceride levels as hypercholesterolemic (n = 26) and mixed-type hyperlipidemic (n = 15) and their risk factors for coronary heart disease including age, sex, hypertension, obesity, smoking, and family history. The patients were started on atorvastatin 10 mg/day, and evaluated within 6-12 weeks to assess the changes in fibrinolytic parameters including global fibrinolytic capacity, plasminogen activator inhibitor type-1 and tissue plasminogen activator, and lipids. After successful lipid-lowering therapy, global fibrinolytic capacity (P = 0.003) and tissue plasminogen activator levels (P = 0.04) were found to be increased and plasminogen activator inhibitor type-1 levels (P = 0.02) decreased in dyslipidemic patients. Global fibrinolytic capacity levels increased (P < 0.001) and plasminogen activator inhibitor type-1 levels decreased (P = 0.01) in patients with hypercholesterolemia (n = 26). However, no significant changes were observed in fibrinolytic parameters in patients with mixed-type hyperlipidemia (n = 15). When the patients were separately evaluated according to risk factors, significant beneficial effects on the fibrinolytic system were observed, especially in patients without obesity and hypertension as well as in older patients and males. These findings suggest that atorvastatin treatment has a beneficial effect on the fibrinolytic system in patients with hypercholesterolemia, but not in patients with mixed-type hyperlipidemia. Further studies are needed to show whether higher doses and longer periods of lipid lowering treatment have beneficial effects in patients with mixed type hyperlipidemia and some risk factors.