MDL 27,531 reduces spontaneous hindlimb contractions in rats with chronic transections of the spinal cord.

Disrupted glycinergic inhibition in the brainstem and spinal cord may contribute to some of the alterations in reflex control seen in patients with spastic disorders. MDL 27,531, which acts functionally like a glycine agonist in its capacity to selectively reverse seizures produced by the glycine antagonist strychnine, was evaluated in a model of spinal injury-induced reflex dysfunction. Rats recovering chronically from complete spinal cord transections exhibited intermittent contractions of the paralyzed hindlimbs, as measured with an automated apparatus. MDL 27,531 selectively decreased these hindlimb contractions, as did the clinically demonstrated antispastic agent clonidine. In its therapeutic dose range, clonidine, but not MDL 27,531, produced ataxia in non-transected rats. These data suggest that MDL 27,531 may be a useful therapeutic agent for the treatment of dysfunctions of reflex control seen in spastic disorders of spinal origin, with potentially fewer side effects than are seen with existing drug therapies.     

Activation of mucosal Vβ3+ T cells and tissue damage in human small intestine by the bacterial superantigen,Staphylococcus aureus enterotoxin B

Staphylococcus aureus enterotoxin B (SEB) was added to explants of fetal human intestine in organ culture or administered into the lumen of fetal small intestine prior to culture. Both routes produced a massive increase in lamina propria T cells expressing Vβ33, and to a lesser extent, those expressing Vβ5 and Vβ12. SEB-activated lamina propria T cells produced interleukin-2 and interferon-Y and T cell activation was accompanied by tissue damage, which was inhibited by FK506.     

Rats fed only during the light period are resistant to stress-induced weight loss

Repeated restraint stress (3 h/day for 3 days) causes a chronic down-regulation of body weight in rats. This study determined whether weight loss was influenced by the time of day that rats had access to food or that stress was applied. Groups of male Sprague-Dawley rats were fed a 40% kcal fat diet with food given ad libitum, only during the light phase or only during the dark phase. After 2 weeks of adaptation, rats within each feeding treatment were divided into four groups. One was exposed to repeated restraint at the start of the light phase, another was restrained at the start of the dark phase and the remaining groups were nonstressed controls for restrained rats. Body weight was significantly reduced in ad libitum- and dark-fed restrained rats, compared with nonstressed controls, from Day 2 of restraint, regardless of the time of day that they were stressed. There was no significant effect of restraint on weight change of light-fed rats. Food intake was inhibited by stress in ad libitum- and dark-fed rats, but it was not changed in light-fed rats. Serum corticosterone was increased by restraint in all rats irrespective of feeding schedule. This study demonstrates that stress-induced weight loss only occurs when rats have food available during their normal feeding period (dark phase) and is not determined by increased corticosterone release.     

The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy

Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias.     

Fully automatic quantification of microarray image data

DNA microarrays are now widely used to measure expression levels and DNA copy number in biological samples. Ratios of relative abundance of nucleic acids are derived from images of regular arrays of spots containing target genetic material to which fluorescently labeled samples are hybridized. Whereas there are a number of methods in use for the quantification of images, many of the software systems in wide use either encourage or require extensive human interaction at the level of individual spots on arrays. We present a fully automatic system for microarray image quantification. The system automatically locates both subarray grids and individual spots, requiring no user identification of any image coordinates. Ratios are computed based on explicit segmentation of each spot. On a typical image of 6000 spots, the entire process takes less than 20 sec. We present a quantitative assessment of performance on multiple replicates of genome-wide array-based comparative genomic hybridization experiments. By explicitly identifying the pixels in each spot, the system yields more accurate estimates of ratios than systems assuming spot circularity. The software, called, runs on Windows platforms and is available free of charge for academic use.     

The educational impact of ACGME limits on resident and fellow duty hours: a pre-post survey study.

PURPOSE: To assess the educational impact of Accreditation Council for Graduate Medical Education resident work-hour limits implemented in July 2003. METHOD: All trainees in all 76 accredited programs at two large teaching hospitals were surveyed between May and June 2003 (before work-hour reductions) and then between May and June 2004 (after work-hour reductions) about hours, education, and fatigue. Based on changes in weekly duty hours, 13 programs experiencing substantial reduction in hours were classified into a reduced-hours group. Differences in assessments of educational endpoints before and after policy implementation by trainees in the reduced-hours group were compared with those in other programs to control for potential temporal trends, using two-way ANOVA with interaction. RESULTS: The number of respondents was 1,770 (60% response rate). The reduced-hours group reported a significant decrease in time spent directly caring for patients (from 48.5 to 42.3 mean h/wk, P = 0.03), but the volume of important clinical experiences, including procedures, was preserved, as was the sense of clinical preparedness. On 22 questions related to educational quality and adequacy, only three differences in differences were significant, with the reduced-hours group reporting a relative increase in opportunities for research, decrease in quality of faculty teaching, and decrease in educational satisfaction. The percentage of trainees reporting frequent negative effects of fatigue dropped more in the reduced-hours programs than in the other programs (P < 0.05). CONCLUSION: This study shows that it may be possible to reduce residents' hours--and the perceived adverse impact of fatigue--while generally preserving the self-assessed quality, quantity, and outcomes of graduate medical education.     

Familial testicular cancer: interest in genetic testing among high-risk family members.

PURPOSE: This study is part of an ongoing National Cancer Institute multidisciplinary, etiologically-focused, cross-sectional study of Familial Testicular Cancer (FTC). The current report targets interest in clinical genetic testing for susceptibility to FTC. METHODS: Demographics, knowledge, health beliefs, and psychological and social factors were evaluated as covariates related to interest in genetic testing. RESULTS: The majority (66%) of 229 participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple-case FTC families expressed interest in having a genetic test within 6 months, should such a test become available. Interest was similar among the three subgroups mentioned above. Worries about insurance discrimination based on genetic test results were associated with a significantly lower interest in testing. Alternatively, participants were more likely to be interested in genetic testing if they were younger and had higher levels of family support, a physician's recommendation supporting testing, cancer distress, and a need for information to inform the health care of their children. CONCLUSIONS: This study reveals social and relationship factors that FTC survivors and their relatives considered important when contemplating the use of new genetic technologies. This is the first study describing hypothetical interest in genetic testing for familial testicular cancer.     

Hypoplasia of the cerebellar vermis and corpus callosum in thrombocytopenia with absent radius syndrome on MRI studies

Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%) associated with mental retardation. In those cases, the mental deficiency is presumed to be a consequence of intracranial hemorrhage due to the thrombo-cytopenia. We report on 2 infants with TAR syndrome. One had developmental delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI). Such findings have not been noted in the literature, but may not have been investigated in most cases. The other infant with TAR syndrome, who has had normal psychomotor development, has a normal brain on MRI scan. Detailed neuroimaging studies, preferably MRI, should be considered in the evaluation of patients with TAR syndrome, especially when there are documented signs of developmental delay, with or without a history of intracranial hemorrhage. © 1994 Wiley-Liss, Inc.     

Triggering of preprogrammed movements as reactions to masked stimuli

1. Visual stimuli were presented to normal human subjects to test simple and more complex voluntary motor responses. Large and small visual stimuli were presented. In some trials, the small stimulus was followed 50 ms later by the large stimulus, so that the small stimulus was not perceived; this is the phenomenon of "backward masking." 2. Although subjects were not able to detect the masked, visual stimulus on forced-choice testing, they performed motor, reaction-time (RT) tasks in response to it. The RTs for responses to the masked stimulus were the same as those for responses to the easily perceived, nonmasked stimulus. 3. This result confirms and extends the findings of Fehrer and Biederman and was demonstrated with both simple and more complex motor responses. 4. Discussion of the findings focuses on their implications for motor control, particularly with respect to the preprogramming of voluntary movement.