Early Biomarkers from Conventional and Delayed-Contrast MRI to Predict the Response to Bevacizumab in Recurrent High-Grade Gliomas.

BACKGROUND AND PURPOSE: The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab. MATERIALS AND METHODS: Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, ≥1 year) and nonresponders (overall survival, <1 year) was studied. The lesion volumes at baseline and the changes in lesion volumes 1 month after treatment initiation, calculated from standard and delayed-contrast MRIs, were studied as possible predictors of outcome. In scans acquired at progression, the average change in lesion volume from previous follow-up in standard and delayed-contrast MRIs was compared. RESULTS: Response and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast-enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response-assessment maps. CONCLUSIONS: The benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma.

Temporal reproduction and its neuroanatomical correlates in adults with attention deficit hyperactivity disorder and their unaffected first-degree relatives.

BACKGROUND: Little is known about time perception, its putative role as cognitive endophenotype, and its neuroanatomical underpinnings in adults with attention deficit hyperactivity disorder (ADHD). METHOD: Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 typically developing controls matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional grey-matter volumes. Temporal processing was investigated as a putative cognitive endophenotype using a temporal reproduction paradigm. General linear modelling was employed to examine the relationship between temporal reproduction performances and grey-matter volumes. RESULTS: ADHD participants were impaired in temporal reproduction and unaffected first-degree relatives performed in between their ADHD probands and typically developing controls. Increased grey-matter volume in the cerebellum was associated with poorer temporal reproduction performance. CONCLUSIONS: Adults with ADHD are impaired in time reproduction. Performances of the unaffected first-degree relatives are in between ADHD relatives and controls, suggesting that time reproduction might be a cognitive endophenotype for adult ADHD. The cerebellum is involved in time reproduction and might play a role in driving time performances.

Treatment of moderate hallux valgus by percutaneous, extra-articular reverse-L Chevron (PERC) osteotomy.

AIMS: The aim of this study was to report a single surgeon series of consecutive patients with moderate hallux valgus managed with a percutaneous extra-articular reverse-L chevron (PERC) osteotomy. PATIENTS AND METHODS: A total of 38 patients underwent 45 procedures. There were 35 women and three men. The mean age of the patients was 48 years (17 to 69). An additional percutaneous Akin osteotomy was performed in 37 feet and percutaneous lateral capsular release was performed in 22 feet. Clinical and radiological assessments included the type of forefoot, range of movement, the American Orthopedic Foot and Ankle (AOFAS) score, a subjective rating and radiological parameters. The mean follow-up was 59.1 months (45.9 to 75.2). No patients were lost to follow-up. RESULTS: The mean AOFAS score increased from 62.5 (30 to 80) pre-operatively to 97.1 (75 to 100) post-operatively. A total of 37 patients (97%) were satisfied. At the last follow up there was a statistically significant decrease in the hallux valgus angle, the intermetatarsal angle and the proximal articular set angle. The range of movement of the first metatarsophalangeal joint improved significantly.. There was more improvement in the range of movement in patients who had fixation of the osteotomy of the proximal phalanx. CONCLUSION: Preliminary results of this percutaneous approach are promising. This technique is reliable and reproducible. Its main asset is that it maintains an excellent range of movement. TAKE HOME MESSAGE: The PERC osteotomy procedure is an effective approach for surgical management of moderate hallux valgus which combines the benefits of percutaneous surgery with the versatility of the chevron osteotomy whilst maintaining excellent first MTPJ range of motion.

Divergent subcortical activity for distinct executive functions: stopping and shifting in obsessive compulsive disorder.

BACKGROUND: There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined. METHOD: We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression. RESULTS: Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation. CONCLUSIONS: OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression.

Take it or leave it: prefrontal control in recreational cocaine users.

Though stimulant drugs such as cocaine are considered highly addictive, some individuals report recreational use over long periods without developing dependence. Difficulties in response inhibition have been hypothesized to contribute to dependence, but previous studies investigating response inhibition in recreational cocaine users have reported conflicting results. Performance on a stop-signal task was examined in 24 recreational cocaine users and 32 healthy non-drug using control participants matched for age, gender and verbal intelligence during functional magnetic resonance imaging scanning. The two groups were further matched on traumatic childhood histories and the absence of family histories of addiction. Results revealed that recreational cocaine users did not significantly differ from controls on any index of task performance, including response execution and stop-signal reaction time, with the latter averaging 198 ms in both groups. Functional magnetic resonance imaging analyses indicated that, compared with controls, stopping in the recreational users was associated with increased activation in the pre-supplementary motor area but not the right inferior frontal cortex. Thus, findings imply intact response inhibition abilities in recreational cocaine users, though the distinct pattern of accompanying activation suggests increased recruitment of brain areas implicated in response inhibition. This increased recruitment could be attributed to compensatory mechanisms that enable preserved cognitive control in this group, possibly relating to their hypothetical resilience to stimulant drug dependence. Such overactivation, alternatively, may be attributable to prolonged cocaine use leading to neuroplastic adaptations.

Punishment promotes response control deficits in obsessive-compulsive disorder: evidence from a motivational go/no-go task.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with response inhibition deficits under motivationally neutral contingencies. We examined response inhibition performance in the presence of reward and punishment. We further investigated whether the hypothesized difficulties in flexibly updating behaviour based on external feedback in OCD would also lead to a reduced ability to adjust to changes in the reward and punishment contingencies. METHOD: Participants completed a go/no-go task that used punishments or rewards to promote response activation or suppression. The task was administered to OCD patients free of current Axis-I co-morbidities including major depression (n = 20) and a group of healthy controls (n = 32). RESULTS: Compared with controls, patients with OCD had increased commission errors in punishment conditions, and failed to slow down immediately after receiving punishment. The punishment-induced increase in commission errors correlated with self-report measures of OCD symptom severity. Additionally, patients did not differ from controls in adapting their overall response style to the changes in task contingencies. CONCLUSIONS: Individuals with OCD showed reduced response control selectively under punishment conditions, manifesting in an impulsive response style that was related to their current symptom severity. This stresses failures of cognitive control in OCD, particularly under negative motivational contingencies.

Inhibition of thoughts and actions in obsessive-compulsive disorder: extending the endophenotype?

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with impairments in stop-signal inhibition, a measure of motor response suppression. The study used a novel paradigm to examine both thought suppression and response inhibition in OCD, where the modulatory effects of stimuli relevant to OCD could also be assessed. Additionally, the study compared inhibitory impairments in OCD patients with and without co-morbid depression, as depression is the major co-morbidity of OCD. METHOD: Volitional response suppression and unintentional thought suppression to emotive and neutral stimuli were examined using a novel thought stop-signal task. The thought stop-signal task was administered to non-depressed OCD patients, depressed OCD patients and healthy controls (n=20 per group). RESULTS: Motor inhibition impairments were evident in OCD patients, while motor response performance did not differ between patients and controls. Switching to a new response but not motor inhibition was affected by stimulus relevance in OCD patients. Additionally, unintentional thought suppression as measured by repetition priming was intact. OCD patients with and without depression did not differ on any task performance measures, though there were significant differences in all self-reported measures. CONCLUSIONS: Results support motor inhibition deficits in OCD that remain stable regardless of stimulus meaning or co-morbid depression. Only switching to a new response was influenced by stimulus meaning. When response inhibition was successful in OCD patients, so was the unintentional suppression of the accompanying thought.

Apparent idiopathic interface disease in a Boer billy goat.

An apparently idiopathic interface diseasee in a 2-year-old Boer billy goat is described. Clinical features of the disease were the presence of a pruritic multiple focally disseminated dermatitis with flat-topped, angular, scaly plaques and papules with corrugated surfaces in the skin of virtually the entire body. The aetiology of the disorder in the described case is unknown.

Udder disease etiology, milk somatic cell counts and NAGase activity in Israeli Assaf sheep throughout lactation.

Bacterial pathogens causing udder infections in Israeli Assaf dairy sheep were identified and changes occurring throughout lactation were monitored to study the correlation between the contaminant and the severity of the infection, as measured by somatic cell count (SCC) and NAGase tests. A total of 159 Israeli Assaf dairy sheep on one farm, in their first (69), second (13) or third and more (77) lactations were included in this study. Udder halves were tested for bacterial condition, SCC and NAGase activity 2-3 weeks post lambing and every 4 weeks after until drying-off. At first sampling, in 60.7% (193/318 quarters) of the halves no bacterial growth (NBG) was detected. Different species of coagulase negative staphylococci (CNS) were the main pathogen group in infected udders. Streptococci were isolated from 14 halves, most of them in the two udder halves. The percent of udder infection in sheep in their third or further lactations was 2.8 greater (P<0.05) than in that of sheep in their first lactation. During the lactation, 90.6% of the halves did not change their classification status, suggesting that most infections occur before lambing and/or during the following first few days. The arithmetic mean of SCC and NAGase of total half udder milk and samplings (during the lactation) were 1144+/-48x10(3)cells/ml and 49.4+/-2.5, respectively. The average SCC in the milk of halves classified as NBG was 321+/-35x10(3)cells/ml and was not significantly changed during the lactation period. In halves infected with CNS, average SCC was 1371+/-150x10(3)cells/ml at the first testing and increased to 2129+/-347x10(3)cells/ml at drying-off. No significant differences were found in SCC and NAGase activity between the different species of the CNS. The mean SCC over the types of bacteria isolated, lactation number and days in lactation was significantly different (P<0.0001). In 4% of the halves, from all samples, SCC was above 5000x10(3)cells/ml although no bacteria were detected in their milk. The higher SCC in the CNS infected halves contrasted with the more moderate SCC found in dairy cows similarly infected, suggesting that the sheep udder has a lower resistance and an augmented immunological response against this group of bacteria. Thus, this should be considered accordingly in schemes for sheep's milk quality payment.

Oral rabies vaccination of red foxes and golden jackals in Israel: preliminary bait evaluation.

Field trials were conducted in late April to early May of 1995 and 1996 in central Israel to assess the potential for controlling rabies in red foxes (Vulpes vulpes) and golden jackals (Canis aureus) by using vaccine-laden baits. Of the bait types which were field tested, polymer fish meal baits were selected as the most suitable for both species. Fish meal baits containing tetracycline hydrochloride, an oral biomarker, were distributed by four-wheel-drive vehicle at a density of approximately 30 baits/km2 in two test areas of 35 km2. Of the animals which were trapped and euthanized seven to ten days after treatment, 65% of foxes and 56% of jackals gave positive results when tested for the biomarker. These results indicate the potential effectiveness of oral rabies vaccination of these species in Israel and possibly elsewhere in the Middle East, where rabies is a problem in wild canids.

Neurologic manifestations in familial Mediterranean fever.

Neurologic involvement in children with familial Mediterranean fever is relatively uncommon and rarely described in the pediatric literature. Although headaches occur frequently, meningitis and convulsions are rare. Thirteen of 101 children with familial Mediterranean fever developed neurologic manifestations. Of these 13 patients, 10 had headaches during acute episodes of the fever. Two patients had convulsions with fever before the age of 5 years; the convulsions and acute episodes recurred at ages 9 and 10 years. Another patient had two episodes of aseptic meningitis followed by convulsive disorder before the diagnosis of familial Mediterranean fever was made; his convulsions were resistant to antiepileptic drugs alone and subsided only when colchicine was added. The possibility of neurologic involvement should be considered in patients with familial Mediterranean fever.

Autografted minced muscle fragments do not affect muscle regeneration in partially excised rat gastrocnemius muscle.

The kinetics of the regeneration process following partial excision or mincing in the rat gastrocnemius muscle was compared using histological and physiological methods. Immediately following injury there was a marked decrease in the distance of shortening (DS) values during isotonic contraction, followed by a progressive increase until 2 weeks after injury. By 85 days the DS values attained those of control muscle during contraction against low loads (up to 50 g), and 80 and 62% of control values at 150 and 250 g, respectively. However, there was no difference in the DS values at 28 and 85 days after injury between muscles that were partially excised or when the removed part of the muscle was minced and placed in the injured site. It is concluded that the enrichment of an injured area of the gastrocnemius muscle with minced autografted muscle does not result in long-term improvement of the functional capacity of the regenerated muscle due to the addition of satellite cells and/or other factors in the minced tissue.

Corpus callosum transection reduces binocularity of cells in the visual cortex of adult cats.

The possible involvement of the corpus callosum in binocular functions of the visual cortex was studied in adult cats. Unit recording was made in areas 17, 18 boundary following posterior or complete transection of the corpus callosum, acutely as well as chronically, after short (3-4 months) and long (5.5-39 months) survival periods. A considerable reduction of binocularly driven cells was found in the posteriorly callosally transected cats (acute: 41% cells; short-chronic: 65%; long-chronic: 32%). Similar results, albeit smaller in the long-survival group, were found following complete callosal transection. In comparison, the proportion of binocular cells in the normal cats was 85%. It was concluded that the corpus callosum is involved in interhemispheric integration and enhancement of binocularity in visual cortex cells. No recovery occurs as function of time following cancellation of the interhemispheric interaction by callosal transection.

Temporary space maintainers retained with composite resin. Part II: Fracture load in vitro.

The average fracture load during occlusal loading of pontics which were bonded to natural abutment teeth in vitro was found to be 56.1, 57.5 and 74.2 kg for natural, acrylic resin, and Restodent pontics, respectively. Coating the roots of the abutment teeth with a thin layer of silicone rubber before embedding them in stone slightly reduced the strength of the fixed partial dentures. Thermocycling the specimens with coated roots caused a considerable decrease in strength to fracture loads of 33.0, 17.9, and 37.3 kg for natural, acrylic resin, and Restodent pontics, respectively. Fracture of the enamel of natural tooth pontics was observed in a few specimens. The superior strength of the fixed partial dentures with natural tooth and Restodent pontics would indicate that these pontics are superior for clinical trials rather than acrylic resin pontics.

Structural and kinetic studies on the solubilization of lecithin by sodium deoxycholate.

Mixed dispersions of egg phosphatidylcholine (PC) and the bile salt sodium deoxycholate (DOC) were prepared by various methods, and their turbidities and proton magnetic resonance spectra were studied as a function of time. The spectra of dispersions prepared by dissolving both components in a common organic solvent and replacing the organic solvent by water did not change with time, indicating that the mixed aggregates formed represent "a state of equilibrium". In the 1H NMR spectra of these mixed aggregates, only signals from small mixed micellar structures were narrow enough to be observed. The dependence of the NMR line widths on the molar ratio of DOC to PC (R) is interpreted in terms of a model for the PC--DOC mixed micelles, according to which PC is arranged as a curved bilayer, the curvature of which increases with increasing R. Upon mixing PC with aqueous solutions of DOC, we found that the mixed aggregates formed are slowly reorganized and ultimately reach the same state of equilibrium. This reorganization was found to be a pseudo-first-order process, the rate constant of which depends linearly upon the detergent concentration. This process involves saturation of the outer bilayers of the multilamellar PC by detergent, followed by transformation of these bilayers into mixed micelles. It is concluded that the solubilization occurs through consecutive "peeling off" of lecithin bilayers.