Direct 16S/18S rRNA Gene PCR Followed by Sanger Sequencing as a Clinical Diagnostic Tool for Detection of Bacterial and Fungal Infections: a Systematic Review and Meta-Analysis.

rRNA gene Sanger sequencing is being used for the identification of cultured pathogens. A new diagnostic approach is sequencing of uncultured samples by using the commercial DNA extraction and sequencing platform SepsiTest (ST). The goal was to analyze the clinical performance of ST with a focus on nongrowing pathogens and the impact on antibiotic therapy. A literature search used PubMed/Medline, Cochrane, Science Direct, and Google Scholar. Eligibility followed PRISMA-P criteria. Quality and risk of bias were assessed drawing on QUADAS-2 (quality assessment of diagnostic accuracy studies, revised) criteria. Meta-analyses were performed regarding accuracy metrics compared to standard references and the added value of ST in terms of extra found pathogens. We identified 25 studies on sepsis, infectious endocarditis, bacterial meningitis, joint infections, pyomyositis, and various diseases from routine diagnosis. Patients with suspected infections of purportedly sterile body sites originated from various hospital wards. The overall sensitivity (79%; 95% confidence interval [CI], 73 to 84%) and specificity (83%; 95% CI, 72 to 90%) were accompanied by large effect sizes. ST-related positivity was 32% (95% CI, 30 to 34%), which was significantly higher than the culture positivity (20%; 95% CI, 18 to 22%). The overall added value of ST was 14% (95% CI, 10 to 20%) for all samples. With 130 relevant taxa, ST uncovered high microbial richness. Four studies demonstrated changes of antibiotic treatment at 12% (95% CI, 9 to 15%) of all patients upon availability of ST results. ST appears to be an approach for the diagnosis of nongrowing pathogens. The potential clinical role of this agnostic molecular diagnostic tool is discussed regarding changes of antibiotic treatment in cases where culture stays negative.

Baseline values but not treatment-induced changes in carotid intima-media thickness predict incident cardiovascular events in treated hypertensive patients: findings in the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND: Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown. METHODS AND RESULTS: Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan-Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, differences in IMT compared with baseline did not predict cardiovascular outcomes. Although on-treatment rather than baseline IMT values significantly entered some of the proportional-hazards models, baseline and on-treatment IMTs were highly correlated, and therefore these results are inconclusive. CONCLUSIONS: ELSA shows that carotid intima-media thickening and plaques are important added risks of cardiovascular outcomes in a treated hypertensive population independently of blood pressure and traditional risk factors. However, the analysis failed to show a predictive role of treatment-dependent IMT changes. These negative conclusions should be tempered by the limitations inherent in the smallness of these changes compared with the large individual differences in baseline IMTs.

The 5.5-year results of MegaOATS--autologous transfer of the posterior femoral condyle: a case-series study.

INTRODUCTION: Large osteochondral defects of the weight-bearing zones of femoral condyles in young and active patients were treated by autologous transfer of the posterior femoral condyle (large osteochondral autogenous transplantation system (MegaOATS)). The technique presented is a sound and feasible salvage procedure to address large osteochondral defects in weight-bearing zones. METHODS: Thirty-six patients between July 1996 and December 2000 were included. Thirty-three patients (10 females, 23 males) were evaluated by the Lysholm score and X-ray scans. A random sample of 16 individuals underwent magnetic resonance imaging analysis. The average age at the date of surgery was 34.3 (15 to 59) years, and the mean follow up was 66.4 (46 to 98) months. The mean defect size was 6.2 (2 to 10.5) cm2, in 27 patients affecting the medial femoral condyle and in six patients affecting the lateral femoral condyle. Trauma or osteochondrosis dissecans were pathogenetic in 82%. RESULTS: The Lysholm score in all 33 individuals showed a highly significant increase from a preoperative median 49.0 points to a median 86.0 points (P < or = 0.001). Twenty-seven patients returned to recreational sports. X-ray scans showed a rounding of the osteotomy edge in 24 patients, interpreted as a partial remodelling of the posterior femoral condyle. Preoperative osteoarthritis in 17 individuals was related to significant lower Lysholm scores (P = 0.014), but progression in 17 patients did not significantly influence the score results (P = 0.143). All 16 magnetic resonance imaging examinations showed vital and congruent grafts. CONCLUSION: Patients significantly improve in the Lysholm score, in daily-life activity levels and in return to recreational sports. Thirty-one out of 33 patients were comfortable with the results and would undergo the procedure again. The MegaOATS technique is therefore recommended as a salvage procedure for young individuals with large osteochondral defects in the weight-bearing zone of the femoral condyle.

The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas.

Endometrial cancer is the most common gynecologic cancer in the developed world. The cell-adhesion protein E-cadherin acts as a tumor-suppressor protein and is down-regulated by the transcription factor Snail, whose expression was shown to be associated with estrogen receptor signaling. This study aimed to investigate the expression of E-cadherin, Snail, and estrogen-receptor alpha in 87 primary tumors and 26 metastases of endometroid endometrial carcinomas. Reduced E-cadherin immunoreactivity was seen in 44.8% of the primary tumors and 65.4% of the metastases with a statistical correlation to higher tumor grade (P=0.003) only in metastatic lesions. About 28.7% of primary tumor specimens showed a positive Snail immunoreactivity that was correlated with reduced estrogen-receptor alpha expression (P=0.047). Positive Snail immunoreactivity was also seen in 53.8% of the metastases where it was correlated with higher tumor grade (P=0.003) and abnormal E-cadherin expression (P=0.003). Interestingly, a Snail expressing endometrial carcinoma-cell line showed a higher migration potential than a variant of this cell line with low levels of Snail. Taken together, our data are in line with a proposed role for Snail in endometrial tumor progression.

Submucosal endoscopy: a novel approach to en bloc endoscopic mucosal resection (with videos).

BACKGROUND: The submucosal layer is of eminent importance for endoscopic mucosal resection (EMR) in the GI tract. OBJECTIVE: Development of submucosal endoscopy, which allows diagnostic and therapeutic endoscopy of the submucosal space (SS) in the esophagus. DESIGN: Acute experiments in a live porcine model. INTERVENTIONS: An area in the esophagus was marked with a diathermic probe to define a mucosal piece for resection. After local infiltration, a 1- to 2-cm transverse incision was performed 1 to 2 cm proximal and distal of these margins. We entered the SS with a flexible small-caliber videoendoscope through the proximal incision and dissected the fibrous submucosal connective tissue in a longitudinal direction with a blunt forceps. For EMR, the lifted mucosa was subsequently separated by use of an insulated-tip hook needle-knife. MAIN OUTCOME MEASUREMENTS: En bloc resection of prespecified mucosal areas. RESULTS: A total of 15 mucosal pieces were resected in 4 pigs. The size of the resected pieces varied from 1.6 cm x 0.9 cm to 7.4 cm x 1.7 cm ex vivo. In a fifth pig, 2 circular mucosectomies (lengths 3.0 cm and 1.6 cm) were done. All mucosal pieces could be completely resected en bloc. The endoscopic view in the SS was excellent. There were no procedure-related complications. LIMITATIONS: The method has not yet been evaluated in humans. CONCLUSIONS: Entering the SS for submucosal endoscopy is a novel, innovative, and practicable method for the dissection of mucosal neoplastic lesions. We demonstrated that mucosal areas of various sizes could be resected en bloc without complications.

Midazolam-pain, but one cannot remember it: a survey among Southern German endoscopists.

BACKGROUND: Benzodiazepines, especially midazolam, are the most frequently used agents for gastrointestinal endoscopy worldwide. Among other parameters the quality of sedation is determined by patients' satisfaction assessed after endoscopy. This approach is misleading as the potent amnestic effect of midazolam conceals pain actually suffered during the endoscopic procedure involving distraction of the endoscopists from their actual tasks by audible reactions and defense movements. In this study, we eliminated the influence of patients' amnesia on the assessment of the quality of sedation and rather interviewed endoscopists and their assistant personnel about their experience with midazolam sedation. We replaced the mostly vague term 'compliance' by terms which unequivocally describe the reactions of the patient during an unpleasant endoscopy. METHODS: A short survey consisting of 12 questions was developed. The questionnaires were distributed to the participants - 115 endoscopists and their assistants - of a tutorial about sedation for gastrointestinal endoscopy in three major Southern German cities. The questionnaire retrieved the endoscopists' experience regarding patients' discomfort or pain under sedation with midazolam, their wish for better sedative agents, their preferred sedative regimens, their medical specialty and their professional experience. RESULTS: Participants were highly experienced with the majority having more than 10,000 procedures and a median of 18 years of endoscopic experience; 77% of endoscopists utilized midazolam for sedation. Ninety-eight percent of the questioned physicians felt that patients have pain during endoscopy with midazolam+/-opioid, but do not remember later. Ninety-two percent reported that it happens that patients moan aloud because of pain and almost half of the endoscopists (48%) reported of screaming. The majority of the endoscopists (91%) reported fierce defense movements with midazolam or the need to hold the patient down on the examination couch because of fierce movements, respectively (75%). Seventy percent of the endoscopists wished to have the rooms for endoscopy preferably soundproof away from the waiting room and 93% wished for better sedative agents. CONCLUSIONS: Midazolam was rated as insufficient for sedation by both endoscopists and their assistant personnel. A wish for better sedative drugs exists.

Sevoflurane affects neurogenesis after forebrain ischemia in rats.

BACKGROUND: The effect of sevoflurane on the neuroregenerative potential after neuronal injury is unclear. We investigated the effect of low and high concentrations of sevoflurane on endogenous neurogenesis after cerebral ischemia. METHODS: Anesthetized and ventilated rats were randomized to four different treatment groups. Groups 1 and 2: 1.4% sevoflurane; Groups 3 and 4: 2.8% sevoflurane. In Groups 1 and 3, no cerebral ischemia was induced (sham-operated). In Groups 2 and 4, 10 min of forebrain ischemia was induced by bilateral carotid artery occlusion plus hemorrhagic hypotension. Physiological variables were maintained constant. Bromodeoxyuridine was given as a marker of neurogenesis. After 28 days brains were perfused. Histopathological damage of the hippocampus was evaluated in hematoxylin and eosin (HE) stained sections using the HE-index (0 = no damage; 1 = 1%-10% damage; 2 = 11%-50% damage; 3 = 51%-100% damage). Immunohistochemistry was used to detect bromodeoxyuridine-positive neurons. Eight untreated rats were investigated as naive controls (Group 5). RESULTS: In neither sham-operated group was histopathological damage or change in neurogenesis observed compared to naive controls. In rats anesthetized with 1.4% sevoflurane, cerebral ischemia caused mild neuronal damage (HE-index of 0.64 +/- 0.84) and increased neurogenesis by 60% when compared with respective sham-operated animals; with 2.8% sevoflurane, the HE-index was 1.22 +/- 1.14, and the number of newly generated neurons increased by 230% when compared with respective sham-operated animals. CONCLUSION: The present data suggest that high concentrations of sevoflurane stimulate neurogenesis in the dentate gyrus after cerebral ischemia.

Comparison between breast volume measurement using 3D surface imaging and classical techniques.

Quantification of the complex breast region can be helpful in breast surgery, which is shaped by subjective influences. However, there is no generally recognized method for breast volume calculation. Three-dimensional (3D) body surface imaging represents a new alternative for breast volume computation. The aim of this work was to compare breast volume calculation with 3D scanning and three classic methods, focusing on relative advantages, disadvantages, and reproducibility. Repeated breast volume calculations of both breasts in six patients (n=12) were performed using a 3D laser scanner, nuclear magnetic resonance imaging (MRI), thermoplastic castings, and anthropomorphic measurements. Mean volumes (cc) and mean measurement deviations were calculated, and regression analyses were performed. MRI showed the highest measurement precision, with a mean deviation (expressed as a percentage of mean breast volume) of 1.56+/-0.52% compared with 2.27+/-0.99% for the 3D scanner, 7.97+/-3.53% for thermoplastic castings, and 6.26+/-1.56% for the anthropomorphic measurements. Breast volume calculations using MRI showed the best agreement with 3D scanning measurement (r=0.990), followed by anthropomorphic measurement (r=0.947), and thermoplastic castings (r=0.727). Compared with three classical methods of breast volume calculation, 3D scanning provides acceptable accuracy for breast volume measurements, better spatial interpretation of the anatomical area to be operated on (due to lack of chest deformation), non-invasiveness, and good patient tolerance. After this preliminary study and further development, we believe that 3D body surface scanning could provide better preoperative planning and postoperative control in everyday clinical practice.

The effect of electroencephalogram-targeted high- and low-dose propofol infusion on histopathological damage after traumatic brain injury in the rat.

BACKGROUND: Propofol is commonly used to sedate patients after traumatic brain injury. However, the dose-dependent neuroprotective effects of propofol after head trauma are unknown. We compared histopathological damage after 6 h of electroencephalogram-targeted high- and low-dose propofol infusion in rats subjected to controlled cortical impact (CCI). METHODS: Animals were randomly assigned to CCI/propofol with electroencephalogram burst-suppression-ratio 1%-5% (CCI/lowprop), CCI/propofol with burst-suppression-ratio 30%-40% (CCI/highprop), control group CCI/1.0 vol % halothane (CCI/halo), or sham group with halothane anesthesia (SHAM/halo). Brain slices were stained with kresyl violet (KV) and hematoxylin/eosin (HE) to evaluate lesion volume, number of eosinophilic cells, and activation of caspase-3 in the hippocampus. RESULTS: Lesion volume (mm3) and number of eosinophilic cells in the hippocampus did not differ significantly [lesion volumes: CCI/lowprop 31.55 +/- 14.66 (KV) and 53.77 +/- 8.62 (HE); CCI/highprop 33.81 +/- 10.57 (KV) and 52.30 +/- 11.55 (HE); CCI/halo 36.42 +/- 17.06 (KV) and 57.95 +/- 8.49 (HE)]. Activation of caspase-3 occurred in the ipsilateral hippocampus in all CCI-groups. CONCLUSION: Despite different levels of cortical neuronal function, there were no relevant differences in the short-term histopathological damage. These results challenge the view that the neuroprotective effect of propofol relates to the suppression of cerebral metabolic demand.

New aspects of breast volume measurement using 3-dimensional surface imaging.

Precise and objective calculation of breast volume is helpful to evaluate the aesthetic result of breast surgery, but traditional methods are unsatisfactory. Three-dimensional (3D) scanning of the body surface allows reproducible and objective assessment of the complex breast region but requires further investigation before clinical application. The main goal of this study was to investigate the precision and accuracy of breast volume measurement using 3D body scanning. Five independent observers standardized the 3D scanning method using 2 dummy models (n = 200) and examined its applicability with 6 test subjects and 10 clinical patients (n = 2220). Breast volume measurements obtained with the 3D-scanner technology were compared with reference measurements obtained from test subjects through nuclear magnetic resonance imaging. The mean deviation of the breast volume measurements of 1 test subject by all observers, expressed as percentage of volume, was 2.86 +/- 0.98, significantly higher than the deviation for the dummy models, 1.65 +/- 0.42 (P < 0.001). With respect to all clinical patients, the mean measurement precision obtained preoperatively was less precise than that obtained postoperatively (3.31 +/- 1.02 versus 1.66 +/- 0.49, respectively). Interobserver differences in measurement precision were not statistically significant. The mean breast volumes obtained by nuclear magnetic resonance imaging (441.42 +/- 137.05 mL) and 3D scanning (452.51 +/- 141.88 mL) significantly correlated (r = 0.995, P < 0.001). Breast volume measurement with 3D surface imaging represents a sufficiently precise and accurate method to guarantee objective and exact recording.

Effect of ozone on oral cells compared with established antimicrobials.

Ozone has been proposed as an alternative antiseptic agent in dentistry based on reports of its antimicrobial effects in both gaseous and aqueous forms. This study investigated whether gaseous ozone (4 x 10(6) microg m(-3)) and aqueous ozone (1.25-20 microg ml(-1)) exert any cytotoxic effects on human oral epithelial (BHY) cells and gingival fibroblast (HGF-1) cells compared with established antiseptics [chlorhexidine digluconate (CHX) 2%, 0.2%; sodium hypochlorite (NaOCl) 5.25%, 2.25%; hydrogen peroxide (H(2)O(2)) 3%], over a time of 1 min, and compared with the antibiotic, metronidazole, over 24 h. Cell counts, metabolic activity, Sp-1 binding, actin levels, and apoptosis were evaluated. Ozone gas was found to have toxic effects on both cell types. Essentially no cytotoxic signs were observed for aqueous ozone. CHX (2%, 0.2%) was highly toxic to BHY cells, and slightly (2%) and non-toxic (0.2%) to HGF-1 cells. NaOCl and H(2)O(2) resulted in markedly reduced cell viability (BHY, HGF-1), whereas metronidazole displayed mild toxicity only to BHY cells. Taken together, aqueous ozone revealed the highest level of biocompatibility of the tested antiseptics.

Comparison of different radiography systems in an experimental study for detection of forearm fractures and evaluation of the Müller-AO and Frykman classification for distal radius fractures.

OBJECTIVES: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis. RESULTS: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.

Real-time quantitative RT-PCR shows variable, assay-dependent sensitivity to formalin fixation: implications for direct comparison of transcript levels in paraffin-embedded tissues.

Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) is a versatile tool for precise quantification of gene expression. Formalin-fixed and paraffin-embedded (FFPE) tissue is well suited for qRT-PCR, if RNA extraction is optimized and small amplicon sizes are used. However, little is known whether individual assays may show variable sensitivity to fixation. This is of great importance, if a direct comparison of different transcripts is performed within the same sample, such as for mRNA splice variants. We established a cell culture model to test for and quantify differences in performance of individual qRT-PCR assays on FFPE as compared with fresh material, using TaqMan methodology. RNA was isolated from 7 different cell lines either directly or after preparation of a FFPE cell block. RNA from both sources was reverse transcribed and gene expression quantified using 13 different TaqMan assays. All assays allowed highly reproducible target quantification, using both fresh and FFPE-derived cDNA. The 13 assays showed an average Ct difference of 3.2 between fresh and FFPE cells, if identical amounts of cDNA were used as template. However, the Ct shifts varied from 1.8 to 5.1 for individual assays, indicating variable resistance to fixation. These Ct shift differences were statistically highly significant in 27/78 (35%) of all possible combinations of assays. Because the Ct shift remained constant for each assay, they could be used for calculation of correction factors which rendered FFPE-derived expression data highly comparable to those obtained from fresh material, and as a consequence among each other. Thus, a standardized assessment of qRT-PCR assay efficiencies in FFPE allows for precise intraindividual comparison of mRNA species, such as splice variants with different biologic functions, in archival tissues.

Impaired cardiac autonomic nervous activity predicts sudden cardiac death in patients with operated and unoperated congenital cardiac disease.

OBJECTIVES: Sudden cardiac death is a leading cause of mortality in patients with congenital cardiac disease after surgical correction and is potentially preventable. The identification of patients at risk is therefore of major interest. We sought to assess the prognostic value of impaired cardiac autonomic nervous activity in patients with congenital cardiac disease. METHODS: Forty-three consecutive patients with congenital cardiac disease were included in this prospective study. Parameters of heart rate turbulence and heart rate variability were calculated from Holter electrocardiograms. In addition, serum brain natriuretic peptide levels were measured. A combined end point of sudden cardiac death or nearly missed sudden cardiac death was used. RESULTS: During a mean follow up of 27 +/- 12.7 months, 5 patients died, and another 2 were successfully resuscitated. On univariate analysis, both brain natriuretic peptide levels and parameters of heart rate variability and heart rate turbulence were associated with impaired prognosis. On multivariate analysis, pathologic heart rate turbulence was found to be the strongest independent risk stratifier (hazard ratio, 61.5; P < .001). CONCLUSIONS: Impaired cardiac autonomic nervous activity is associated with an increased risk of sudden cardiac death in congenital cardiac disease. Our results suggest that heart rate turbulence might be superior to established markers of cardiac autonomic dysfunction, such as heart rate variability. The combined use of heart rate turbulence, heart rate variability, and markers of neurohormonal activation, such as brain natriuretic peptide, might further improve the prognostic value.

The long-term effect of sevoflurane on neuronal cell damage and expression of apoptotic factors after cerebral ischemia and reperfusion in rats.

We investigated the long-term effects of sevoflurane on histopathologic injury and key proteins of apoptosis in a rat hemispheric ischemia/reperfusion model. Sixty-four male Sprague-Dawley rats were randomly assigned to Group 1 (fentanyl and N2O/O2; control) and Group 2 (2.0 vol% sevoflurane and O2/air). Ischemia (45 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure 40 mm Hg). Animals were killed after 1, 3, 7, and 28 days. In hematoxylin and eosin-stained brain sections eosinophilic hippocampal neurons were counted. Activated caspase-3 and the apoptosis-regulating proteins Bax, Bcl-2, Mdm-2, and p53 were analyzed by immunostaining. No eosinophilic neurons were detected in sevoflurane-anesthetized rats over time, whereas 9%-38% of the hippocampal neurons were eosinophilic (days 1-28) in control animals. On days 1 and 3, the concentration of Bax was 140%-200% larger in fentanyl/N2O-anesthetized animals compared with sevoflurane. Bcl-2 was 100% less in control animals during the first 3 days. Activated caspase-3 was detected in neurons of both groups (0.75%-2.2%). These data support a sustained neuroprotective potency of sevoflurane related to reduced eosinophilic injury after cerebral ischemia/reperfusion.

Detection of consciousness by electroencephalogram and auditory evoked potentials.

BACKGROUND: A set of electroencephalographic and auditory evoked potential (AEP) parameters should be identified that allows separation of consciousness from unconsciousness (reflected by responsiveness/unresponsiveness to command). METHODS: Forty unpremedicated patients received anesthesia with remifentanil and either sevoflurane or propofol. With remifentanil infusion (0.2 microg . kg . min), patients were asked every 30 s to squeeze the investigator's hand. Sevoflurane or propofol was given until loss of consciousness. After intubation, propofol or sevoflurane was stopped until patients followed the command (return of consciousness). Thereafter, propofol or sevoflurane was started again (loss of consciousness), and surgery was performed. Return of consciousness was observed after surgery. The electroencephalogram and AEP from immediately before and after the transitions were selected. Logistic regression was calculated to identify models for the separation between consciousness and unconsciousness. For the top 10 models, 1,000-fold cross-validation was performed. Backward variable selection was applied to identify a minimal model. Prediction probability was calculated. The digitized electroencephalogram was replayed, and the Bispectral Index was measured and accordingly analyzed. RESULTS: The best full model (prediction probability 0.89) contained 15 AEP and 4 electroencephalographic parameters. The best minimal model (prediction probability 0.87) contained 2 AEP and 2 electroencephalographic parameters (median frequency of the amplitude spectrum from 8-30 Hz and approximate entropy). The prediction probability of the Bispectral Index was 0.737. CONCLUSIONS: A combination of electroencephalographic and AEP parameters can be used to differentiate between consciousness and unconsciousness even in a very challenging data set. The minimal model contains a combination of AEP and electroencephalographic parameters and has a higher prediction probability than Bispectral Index for the separation between consciousness and unconsciousness.

Quality control of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The European Lacidipine Study of Atherosclerosis (ELSA) was a prospective, randomized, double-blind, multinational interventional trial using B-mode ultrasound measurement of carotid intima-media thickness (IMT) in 2259 hypertensive individuals. ELSA showed that 4-year treatment with the calcium antagonist, lacidipine, significantly slowed down progression of carotid atherosclerosis as compared with treatment with the beta-blocker, atenolol. OBJECTIVE: To report data on cross-sectional and longitudinal quality control of the ultrasound measurements implemented throughout ELSA. METHODS: Patients underwent scans at baseline and at each annual visit. All endpoints were measured while the study was in progress (initial measurements). In addition to the cross-sectional quality control procedures, a longitudinal quality control procedure of re-reading 250 baseline scans at yearly intervals was implemented, to control possible reader drift. After the study had been completed, the primary endpoint was measured again under the same condition of cross-sectional quality control. RESULTS: Cross-sectional quality control data showed high reliability for all endpoints at all time points except for single maximum IMT (Tmax) and internal carotid IMT. Within-reader reliability was constantly better than between-reader reliability but, for the primary endpoint, between-reader reliability remained excellent. Initial and longitudinal quality control measurements showed a time trend toward lower IMT values. After application of a correction factor calculated from longitudinal quality control, all initial measurements no longer decreased with time, and the corrected IMT measurements were reasonably similar to those made after completion of the study. CONCLUSION: For long-term epidemiological studies and clinical trials, both cross-sectional and longitudinal quality control are critical to the reliability of measurements. In order to evaluate the absolute change in IMT and interpret study results without bias, both must be implemented.

Outcome of operated and unoperated adults with congenital cardiac disease lost to follow-up for more than five years.

Many patients with congenital cardiac disease need a regular cardiologic follow-up (FU) even after successful primary treatment. Nevertheless, many of them are lost to FU. The present study verifies for the first time the outcome of adults with congenital cardiac disease lost to FU of a specialized institution for >5 years.

Chest radiography with a digital flat-panel detector: experimental receiver operating characteristic analysis.

PURPOSE: To evaluate the influence of different detector radiation doses and peak kilovoltage settings on diagnostic performance and radiation dose at posteroanterior (PA) chest radiography performed with an amorphous silicon flat-panel detector (FPD). MATERIALS AND METHODS: All examinations were performed by using a digital FPD. PA chest radiographs of an anthropomorphic chest phantom were obtained with detector radiation doses of 2.50 microGy (system speed, 400), 1.56 microGy (speed, 640), and 1.25 microGy (speed, 800) and with peak kilovoltage values of 100, 120, and 140 kVp. Four types of simulated lesions-nodules of different sizes, polylobulated lesions, interstitial-nodular lesions, and interstitial-reticular lesions-were superimposed on the phantom. After four radiologists assessed all of the images, receiver operating characteristics analysis was performed. In addition, the entrance surface dose was measured and the effective dose was calculated. RESULTS: Reduced detector dose led to significantly decreased diagnostic performance in overall lesion detection (P <.05). However, over pulmonary areas only, this effect could not be seen. With use of the same kilovoltage values, reducing the detector dose, even to 1.25 microGy (speed, 800), did not lead to significantly decreased lesion detectability. In terms of diagnostic performance and effective dose, 120 kVp was the most effective. CONCLUSION: Standard PA chest radiographs should still be acquired at a detector dose of 2.50 microGy (speed, 400) with 120 kVp to yield the highest diagnostic performance. However, when the present analysis was focused on the lung fields only, no significant loss in diagnostic performance could be demonstrated, even after a 50% reduction in radiation dose.

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA).

INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations. METHODS: The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values. CONCLUSION: These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.