In vivo multiple-mouse imaging at 1.5 T.

A multiple-mouse solenoidal MR coil was developed for in vivo imaging of up to 13 mice simultaneously to screen for tumors on a 1.5 T clinical scanner. For the coil to be effective as a screening tool, it should permit acquisition of MRIs in which orthotopic tumors with diameters >2 mm are detectable in a reasonable period of time (<1 hr magnet time) and their sizes accurately measured. Using a spin echo sequence, we demonstrated that this coil provides sufficient sensitivity for moderately high resolution images (156-176 microm in plane-resolution, 1.5 mm slice thickness). This spatial resolution permitted detection of primary brain tumors in transgenic/knockout mice and orthotopic xenografts. Brain tumor size as measured by MRI was correlated with size measured by histopathology (P < 0.001). Metastatic tumors in the mouse lung were also successfully imaged in a screening setting. The multiple mouse coil is simple in construction and may be implemented without any significant modification to the hardware or software on a clinical scanner.     

"Chronic painter''s syndrome". A reanalysis of psychological test data in a group of diagnosed cases, based on comparisons with matched controls

Twenty solvent-exposed workers, most of them painters, had been diagnosed as cases of toxic encephalopathy in 1978/79. Two years later they were re-examined with an extensive battery of neuropsychological tests. Their performance was unchanged on retesting. We have now compared their test results with those of non-exposed control subjects. Previous impressions of significant intellectual impairment in the solvent-exposed patients could not be confirmed when the influence of age, education, and intelligence was taken into consideration. The present group with presumed toxic encephalopathy is assumed to be representative of other patients who were similarly diagnosed in our department. The presently reanalyzed cases had been diagnosed as brain damaged and reported as such in the literature. Thus, they may have contributed to the formation of the concept of the "chronic painters' syndrome" with dementia.     

Brain activation during dichotic presentations of consonant-vowel and musical instrument stimuli: a 15O-PET study

Dichotic listening means that two different stimuli are presented at the same time, one in each ear. This technique is frequently used in experimental and clinical studies as a measure of hemispheric specialization. The primary aim of the present study was to record regional changes in the distribution of cerebral blood flow (CBF) with the 15O-PET technique to dichotically presented consonant-vowel (CV) and musical instrument stimuli, in order to test the basic assumption of differential hemispheric involvement when stimuli presented to one ear dominate over stimuli presented in the other ear. All stimuli were 380 ms in duration with a 1000 ms interstimulus interval, and were presented in blocks of either CV-syllable or musical instrument pairs. Twelve normal healthy subjects had to press a button whenever they detected a CV-syllable or a musical instrument target in a stream of CV- and musical instrument distractor stimuli. The targets appeared equally often in the right and left ear channel. The CV-syllable and musical instrument targets activated bilateral areas in the superior temporal gyri. However, there were significant interactions with regard to asymmetry of the magnitude of peak activation in the significant activation clusters. The CV-syllables resulted in greater neural activation in the left temporal lobe while the musical instruments resulted in greater neural activation in the right temporal lobe. Within-subjects correlations between magnitude of dichotic listening and CBF asymmetry were, however, non-significant. The changes in neural activation were closely mimicked by the performance data which showed a right ear superiority in response accuracy for the CV-syllables, and a left ear superiority for the musical instruments. In addition to the temporal lobe activations, there were activation tendencies in the left inferior frontal lobe, right dorsolateral prefrontal cortex, left occipital lobe, and cerebellum.     

Effects of attention on dichotic listening: an 15O-PET study

The present study investigated the effect of attention on brain activation in a dichotic listening situation. Dichotic listening is a technique to study laterality effects in the auditory sensory modality. Two different stimuli were presented simultaneously, one in each ear. Twelve subjects listened to lists of consonant-vowel syllables, or short musical instrument passages, with the task of detecting a "target" syllable or musical instrument by pressing a button. The target stimulus appeared an equal number of times in the left and right ear. The subjects were instructed to either concentrate on the stimuli presented in both ears, or only on the left or right ear stimulus. Brain activation was measured with 15O-PET, and significant changes in regional normalized counts (rNC) were evaluated using statistical parametric mapping (SPM96) software. Concentrating on either the right or left ear stimulus significantly decreased activity bilaterally in the temporal lobes compared to concentrating on both ear stimuli, at the expense of an increased activation in the right posterior and inferior superior parietal lobe. The CV-syllables activated areas corresponding to the classic language areas of Broca and Wernicke. The musical instrument stimuli mainly activated areas in visual association cortex, cerebellum, and the hippocampus. An interpretation of the findings is that attention has a facilitating effect for auditory processing, causing reduced activation in the primary auditory cortex when attention is explicitly recruited. The observed activations in the parietal lobe during the focused attention conditions could be part of a modality non-specific "attentional network".     

HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression‐free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance to adjuvant chemotherapy, PFS, and overall survival were analyzed in univariate analyses and in multivariate analyses adjusted for age, performance score, surgical outcome, stage, grade, and histological subtype. Serum HE4 levels predicted chemotherapy resistance, PFS, and overall survival correlated significantly (p < 0.001) in the univariate analyses; but after adjustment in a multivariate model, serum HE4 was insignificant, except in a subgroup analysis of postmenopausal women, where serum HE4 significantly predicted resistance to chemotherapy and progression‐free survival. HE4 tissue protein expression predicted PFS (p = 0.022) and overall survival (p = 0.047) in the univariate analysis, while HE4 tissue protein expression failed to predict these outcomes in the adjusted multivariate analyses. Serum HE4 or HE4 tissue protein expression are not independent factors of chemotherapy resistance or survival in patients with EOC, but serum HE4 might predict chemotherapy resistance and PFS in postmenopausal women.     

Preliminary Laboratory Report of Fungal Infections Associated with Contaminated Methylprednisolone Injections

In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although Aspergillus fumigatus was recovered from the index case, Exserohilum rostratum was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials. Exserohilum rostratum was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (n = 67 patients), Tennessee (n = 26), Virginia (n = 20), and Indiana (n = 16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF. E. rostratum antifungal susceptibility MIC₅₀ and MIC₉₀ values were determined for voriconazole (1 and 2 μg/ml, respectively), itraconazole (0.5 and 1 μg/ml), posaconazole (0.5 and 1 μg/ml), isavuconazole (4 and 4 μg/ml), and amphotericin B (0.25 and 0.5 μg/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.