Volume of interest-based [18F]fluorodeoxyglucose PET discriminates MCI converting to Alzheimer's disease from healthy controls. A European Alzheimer's Disease Consortium (EADC) study.

An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs) in each hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine and the AAL VOIs was tested against a validated method (PALZ). At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed.

Intra-Articular Synovial Sarcomas: Incidence and Differentiating Features from Localized Pigmented Villonodular Synovitis.

Purpose. To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal) pigmented villonodular synovitis (PVNS) and if multivariate data analysis could be used as a complementary clinical tool. Methods. Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA), were used. Register data on all synovial sarcomas were extracted for comparison. Results. The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas. Conclusions. The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS.

Pediatric allo-SCT for malignant and non-malignant diseases: impact on health-related quality of life outcomes.

The objective of this study was prospectively to investigate the health-related quality of life (HRQOL) of 80 pediatric recipients of allo-SCT for malignant and non-malignant diseases. The PedsQL 4.0 was used to assess self-reported physical, emotional and social functioning of children 5 years old once, pre-allo-SCT and on days +100, +180, +365 and +730. Emotional and social functioning was stable pre-to-post-allo-SCT and comparable to the normative sample (P>0.05), and physical functioning was 17 points lower pre-allo-SCT (P0.01) with improved scores equivalent to the norms by day +730. Lower physical scores were reflected by 50-54% of children reporting difficulties with movement, strength, pain and fatigue. At baseline, children ages 5-7 reported lower social functioning (P<0.05) and patients with non-malignant disease reported better physical functioning (P<0.05). Emotional functioning in ages 8-12 improved over time (P<0.05). More than 50% of the participants were minority and their HRQOL was similar to non-minority participants. Physical functioning significantly improved for recipients of reduced-toxicity conditioning (P0.01), significantly worsened for patients with chronic GVHD (cGVHD; P<0.05), and significantly decreased in recipients of matched-unrelated donor transplant who developed cGVHD (P<0.05). Multidisciplinary efforts are necessary to identify and support pediatric patients' physical needs to improve functional outcomes.

Cortical morphometric subclassification of frontotemporal lobar degeneration.

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is a primary neurodegenerative disease comprising 3 clinical subtypes: frontotemporal dementia (FTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The subdivision is primarily based on the characteristic clinical symptoms displayed by each subtype. We hypothesized that these symptoms would be correlated to characteristic patterns of brain atrophy, which could be indentified and used for subclassification of subjects with FTLD. MATERIALS AND METHODS: Volumes of 9 cortical regions were manually parcellated and measured on both hemispheres on 27 controls, 12 patients with FTD, 9 patients with PNFA, and 13 patients with SD. The volumetric data were analyzed by traditional t tests and by a multivariate discriminant analysis (partial least squares discriminant analysis). RESULTS: The ensemble or pattern of atrophy was a good discriminator in pair-wise comparison between the subtypes: FTD compared with SD (sensitivity 100% [12/12], specificity 100% [13/13]); FTD compared with PNFA (sensitivity 92% [11/12], specificity 89% [8/9]); and SD compared with PNFA (sensitivity 86% [11/13], specificity 100% [9/9]). Temporal-versus-frontal atrophy was the most important pattern for discriminating SD from the other 2 subtypes. Right-sided versus left-sided atrophy was the most important pattern for discriminating between subjects with FTD and PNFA. CONCLUSIONS: FTLD subtypes generally display a characteristic pattern of atrophy, which may be considered in diagnosing patients with FTLD.

Outbreak of salmonellosis in a restaurant in Stockholm, Sweden, September - October 2006.

The largest outbreak of salmonellosis in 25 years in Stockholm County occurred during September - October 2006. A total of 115 persons who had a meal at a restaurant in Stockholm were notified as cases of salmonellosis through the Swedish surveillance system. The probable vehicle of the outbreak was mung beans, soaked in lukewarm water for 24 hours before being served at the restaurant. These mung beans had been included in all dishes served in the restaurant and the outbreak was terminated when they were excluded from the menu. Either Salmonella Bareilly or Salmonella Virchow were isolated from affected persons. No person was found to have an infection with both serotypes. The majority of affected persons were females with a median age of 34 years. This and similar outbreaks associated with consumption of vegetables and fruits highlight the increasing importance of fresh produce as vehicle for foodborne outbreaks in Europe.

In vitro models for the blood-brain barrier.

The aim of the present study was to identify a model for the blood-brain barrier based on the use of a continuous cell line, and to investigate the specificity of this model. A set of test compounds, reflecting different transport mechanisms and different degrees of permeability, as well as different physiochemical properties was selected. In vivo data for transport across the blood-brain barrier of this set of test compounds was generated as part of the study using two different in vivo models. A computational prediction model was also developed, based on 74 proprietary Pharmacia compounds, previously tested in one of the in vivo models. Molsurf descriptors were calculated and 21 descriptors were correlated with log(Brain(conc.)/Plasma(conc.)) using partial least squares projection to latent structures (PLS). However, the correlation between predicted and measured values was found to be rather low and differed between one and two log units for several of the compounds. The test compounds were analyzed in vitro using primary bovine and human brain endothelial cells co-cultured with astrocytes, and also using two different immortalized brain endothelial cell lines, one originating from rat and one from mouse. Cell models using cells not derived from the blood-brain barrier, ECV/C6, MDCK and Caco-2 cell lines, were also used. No linear correlation between in vivo and in vitro permeability was found for any of the in vitro models when all compounds were included in the analysis. The highest r2 values were seen in the bovine brain endothelial cells (r2=0.43) and MDCKwt (r2=0.46) cell models. Higher correlations were seen when only passively transported compounds were included in the analysis, bovine brain endothelial cells (r2=0.74), MDCKwt (r2=0.65) and Caco-2 (r2=0.86). By plotting in vivo Papp values against logDpH7.4 it was possible to classify compounds into four different classes: (1) compounds crossing the blood-brain barrier by passive diffusion, (2) compounds crossing the blood-brain barrier by blood-flow limited passive diffusion, (3) compounds crossing the blood-brain barrier by carrier mediated influx, and (4) compounds being actively excreted from the brain by active efflux. Papp and Pe values obtained using the different in vitro models were also plotted against logDpH7.4 and compared to the plot obtained when in vivo Papp values were used. Several of the in vitro models could distinguish between passively distributed compounds and efflux substrates. Of the cell lines included in the present study, the MDCKmdr-1 cell line gave the best separation of passively and effluxed compounds. Ratios between AUC in brain and AUC in blood were also calculated for six of the compounds and compared to ratios between Pe or Papp for transport in the apical to basolateral and basolateral to apical direction. Again the MDCKmdr-1 cell line gave the best correlation with only one compound (AZT) giving large discrepancy between in vitro and in vivo data. None of the in vitro models could identify compounds known to be substrates for carrier mediated influxed as such, and the results indicate that a tighter in vitro blood-brain barrier model probably is needed in order to facilitate studies on carrier mediated influx. The findings presented also indicate that identification of "batteries" of in vitro tests are likely to be necessary in order to improve in vitro-in vivo correlations and to make it possible to perform acceptable predictions of in vivo brain distributions from in vitro data.

Is arterial proximity a valid indication for arteriography in penetrating extremity trauma? A prospective analysis.

Three hundred seventy-three patients with a penetrating extremity injury were studied to assess the yield of arteriography. Patients underwent arteriography if any of the following was present: bruit, history of hemorrhage or hypotension, fracture, hematoma, decreased capillary refill, major soft-tissue injury, or nerve or pulse deficit. In the absence of these findings, arteriography was performed if the injury was in "proximity" to a major neurovascular bundle. In 216 patients, arteriography was performed when an abnormal finding was noted. Sixty-five injuries were identified, 19 requiring intervention. Proximity was the indication for arteriography in 157 patients. Seventeen injuries were identified, of which one required repair. In penetrating extremity trauma, the need for arteriography is based on clinical findings. The use of arteriography to screen for an arterial injury when proximity alone is the indication rarely identifies a significant injury and should be abandoned.

Surgical procedures in the management of Takayasu's arteritis.

Takayasu's arteritis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries. Variable results have been reported after medical and surgical management. Twenty female patients with Takayasu's arteritis were treated from 1973 to 1989. Eleven (55%) patients had hypertension. Upper or lower extremity ischemia was present in 12 (60%) patients and cerebrovascular insufficiency in seven (35%). Nine patients initially managed with corticosteroids had no improvement in signs or symptoms of arterial insufficiency. Eleven patients had 16 vascular procedures for the following indications: renovascular hypertension (6), extremity ischemia (5), cerebrovascular insufficiency (2), dilation ascending aorta with aortic insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1). Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra-celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1), and nephrectomy (1). Clinical improvement occurred in all patients. There were no operative deaths. All are alive at a mean follow-up of 5.75 years (6 months to 16 years). Revision of the initial reconstruction has been required for recurrent renovascular hypertension in one patient and extremity ischemia in another. The other nine patients remain symptomatically improved. Symptomatic Takayasu's arteritis frequently requires arterial reconstruction. Symptomatic improvement and excellent long-term graft patency can be expected after arterial reconstruction.

Role of routine arteriography in blunt lower-extremity trauma.

During an 18-month period, 53 patients with unilateral blunt lower-extremity trauma were entered into a prospective study designed to determine how often clinically occult arterial injuries are identified by routine arteriography, and how often these injuries are of sufficient magnitude to warrant therapeutic intervention. Patients underwent diagnostic arteriography if one or more of the following abnormal clinical findings were present: distal pulse deficit, nerve deficit, soft-tissue loss, decreased capillary refill, bruit, or a history of hemorrhage or hypotension. In the absence of these findings, arteriography was performed for significant orthopedic injuries, i.e., knee dislocations or complex long-bone fractures. In 31 patients (58%), arteriography was performed because 1 or more abnormal clinical findings were present and 12 arterial injuries were identified, 4 requiring arterial repair. The presence of a knee dislocation or complex long-bone fracture was the only indication for arteriography in 22 patients (42%) and 3 arterial injuries were identified, none requiring operative intervention. For all patients, two variables, pulse deficit and delayed capillary refill, strongly correlated (p less than 0.05) with arteriographic demonstration of an arterial injury. In the absence of these findings, routine diagnostic arteriography will have a low diagnostic yield and will rarely identify a vascular injury in a major artery that will require operative repair. Arteriography should be selectively performed and guided by examination and noninvasive Doppler indices.

Influence of cornual insemination on endometrial damage and microbial flora in the bovine uterus.

The objectives were to determine effects of cornual insemination on endometrial characteristics and uterine bacterial flora. Forty cows were assigned randomly (10/group) to each of the following treatments: 1) control--no uterine manipulation; 2) uterine body insemination--deposition of the inseminate at the internal cervical os; 3) cornual insemination--one-half of inseminate deposited into each uterine horn anterior to the internal bifurcation and 4) cornual insemination plus endometrial biopsy--insemination into each uterine horn and trauma induced by endometrial biopsy. Animals were slaughtered and reproductive tracts were removed 5 d after treatment. Bacterial populations of the uterine lumen were evaluated by both flushings and swabbings of each horn. Treatment did not influence the presence of luminal bacteria as determined by flushing or swab samples. Gross endometrial characteristics were quantitated in all tracts. Characteristics considered were total endometrial surface area, discolored regions that appeared to be distinctly darker than the remaining portion of the endometrium and obvious surface damage. Discolored regions were evaluated as both total areas and percentage of endometrium. Treatment did not influence total or percent discolored areas. Microscopic evaluation of these tissues revealed increased edema when compared with nondiscolored regions but no disruption of the luminal epithelium was found. Surface damage was found only in the biopsied treatment group. Observation of the endometrium revealed that extensive regeneration occurred by 5 d after treatment. The data suggest that cornual insemination does not result in uterine trauma or bacterial presence 5 d after breeding, and the endometrium is capable of regeneration after trauma during estrus.