Echoes of the electroweak phase transition: discovering a second Higgs doublet through A0→ZH0.

The existence of a second Higgs doublet in nature could lead to a cosmological first-order electroweak phase transition and explain the origin of the matter-antimatter asymmetry in the Universe. We obtain the spectrum and properties of the new scalars H0, A0, and H(±) that signal such a phase transition and show that the observation of the decay A0→ZH0 at LHC would be a "smoking gun" signature of these scenarios. We analyze the LHC search prospects for this decay in the ℓℓbb and ℓℓW(+)W(-) final states, arguing that current data may be sensitive to this signature in the former channel as well as there being great potential for a discovery in either channel at the very early stages of the 14 TeV run.

Spinal cord stimulation in severe, inoperable peripheral vascular disease.

Objective. To assess the effect of spinal cord stimulation in patients with severe, inoperable peripheral vascular disease, and uncontrolled pain. Patients and methods. A case study of 20 patients with end-stage peripheral vascular disease, either Fontaine Class 3 or 4 limb ischemia. All 20 patients implanted with spinal cord stimulation devices with follow-up from one to five years (mean, 32 months) performed in a multidisciplinary pain treatment center. Results. In the 20 patients implanted with a spinal cord stimulator for peripheral vascular disease, overall there was 75% limb salvage; with Fontaine Class 3 patients there was 86% and with Fontaine Class 4 patients, 69% limb salvage of the treated limbs. Conclusions. Twenty patients with end-stage peripheral vascular disease were implanted with spinal cord stimulators and followed for five years, until amputation or end of life, showing excellent results for limb salvage and minimal complications. The current literature regarding the use of spinal cord stimulation for peripheral vascular disease is reviewed, supporting its benefit for limb salvage and pain relief.

Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity.

The tissue-specific expression of major histocompatibility complex class I genes is determined by a series of upstream regulatory elements, many of which remain ill defined. We now report that a distal E-box element, located between bp -309 and -314 upstream of transcription initiation, acts as a cell type-specific enhancer of class I promoter activity. The class I E box is very active in a neuroblastoma cell line, CHP-126, but is relatively inactive in the HeLa epithelial cell line. The basic helix-loop-helix leucine zipper proteins upstream stimulatory factor 1 (USF1) and USF2 were shown to specifically recognize the class I E box, resulting in the activation of the downstream promoter. Fine mapping of USF1 and USF2 amino-terminal functional domains revealed differences in their abilities to activate the class I E box. Whereas USF1 contained only an extended activation domain, USF2 contained both an activation domain and a negative regulatory region. Surprisingly, the naturally occurring splice variant of USF2 lacking the exon 4 domain, U2DeltaE4, acted as a dominant-negative regulator of USF-mediated activation of the class I promoter. This latter activity is in sharp contrast to the known ability of U2DeltaE4 to activate the adenovirus major late promoter. Class I E-box function is correlated with the relative amount of U2DeltaE4 in a cell, leading to the proposal that U2DeltaE4 modulates class I E-box activity and may represent one mechanism to fine-tune class I expression in various tissues.

The clinical usefulness of routine stacked multiplanar reconstruction in helical abdominal computed tomography.

RATIONALE AND OBJECTIVES: The authors evaluate the usefulness of stacked multiplanar reconstructions in routine, thick-section abdominal computed tomography. MATERIALS AND METHODS: Twenty-five routine, thick-section contrast abdominal CTs performed with equivalent technique were reformatted by multiplanar reconstructions in sagittal and coronal planes sequentially from side-to-side and front-to-back. The image sets were submitted, first axial images only followed by axial plus multiplanar reconstructions (MPRs), to 5 separate physician readers including 2 radiologists and 3 nonradiologists. These readers graded the visualization of a variety of normal and up to 5 pathologic lesions per patient on a scale of 1 to 5 (5 = best). RESULTS: The addition of sagittal and coronal multiplanar reconstructions significantly improved the visualization of all normal anatomic structures (mean axial only, 3.8; mean axial plus MPR, 4.1; P < 0.0001). In addition, most pathologic lesions were statistically better visualized with the addition of multiplanar reconstructions (mean axial images only, 3.9; mean axial plus MPR, 4.1; P < 0.0001). All five readers found improved visualization in nearly every category with the addition of the multiplanar reconstructions. However, in only 7% of cases, did a reviewer find new diagnostic information with the addition of MPR images. CONCLUSIONS: Stacked multiplanar reconstructions of routine, thick-section abdominal CT has clinical value in both the display of normal anatomic and pathologic lesions. Further studies, however, are required to confirm these findings before it is commonly used.

Enhanced limb salvage for peripheral vascular disease with the use of spinal cord stimulation.

For patients with peripheral vascular disease that have exhausted all means for surgical repair, spinal cord stimulation is an alternative treatment that could offer them significant pain relief or possibly delay the need for limb amputation. Spinal cord stimulation (SCS) has proven to offer many of these patients a return to a more normal lifestyle by relieving pain to such a degree that their mobility is improved. In addition, increases in blood flow to the affected extremity have helped to improve overall foot salvage. Since SCS is minimally invasive and has few reported complications, it is a viable alternative for patients with multiple health risks, and with proper patient selection and early referral, it can reduce health care costs in many cases.

Clinical experience with controlled-release carbidopa/levodopa in Parkinson's disease.

We converted 158 Parkinson's disease (PD) patients on stable doses of standard carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%) preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients elected to continue L-CR, and we performed the primary data analysis on this group. Following conversion to L-CR, patients reported an increase in length of benefit from each dose and an increased "kick-in" time. There was a decrease in the total number of doses, "off" periods, sleep interruptions per night, dose failures, and sleep disturbances. Conversion to L-CR resulted in a significant increase in total levodopa dose. There was no significant change in the dyskinesias. However, early-morning dystonia resolved in eight of 14 patients. Our findings suggest that L-CR is particularly effective in decreasing motor fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures in PD.

Neuropsychological and event-related potential correlates of nonepileptic seizures.

A retrospective study of 14 patients with epileptic seizures and 11 with nonepileptic seizures, all taking antiepileptic drugs, found epileptic patients had significantly longer P160, N200, and P300 latencies on auditory event-related potential recordings. Patients with nonepileptic seizures had generally higher IQs and significantly greater psychopathology on neuropsychological scales.

Asymmetrical cognitive differences associated with hemiparkinsonism.

The question of whether Parkinson's disease (PD) patients who have left (LPD) or right (RPD) motor predominance also exhibit cognitive differences is controversial. We examined this issue using a neuropsychological battery designed to provide a balanced sampling of both right- and left-hemispheric functions. RPD patients were impaired relative to LPD patients on verbally mediated tasks (left hemisphere function), but there was no group difference for visuospatial tasks (right-hemispheric function). In addition, there was a significant correlation between the extent of right side motor predominance and performance on verbal tasks, but there was no relationship between left side motor symptoms and performance on visuospatial tasks. The controversy related to cognitive differences in hemiparkinsonism may be due to the balance of the assessment procedure, the severity of motor asymmetry, or both.

Metabolism of glucurolactone to glucarate in Parkinson's disease.

The metabolism of oral glucurolactone to serum D-glucarate by the hepatic cytochrome P450 enzyme system was no different in 20 untreated Parkinson's disease (PD) patients as compared with 20 age- and sex-matched controls. There was no evidence for a deficit in hepatic enzymes in PD.

Olfactory function in essential tremor.

Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD.

Emotional changes with multiple sclerosis and Parkinson's disease.

Multiple sclerosis (MS) and Parkinson's disease (PD) are relatively common neurological disorders. Both disorders are chronic and progressive, produce varying degrees of physical disability, and result in characteristic neuropathological changes to a variety of subcortical brain structures. Patients with MS or PD also exhibit a higher prevalence of emotional disorders relative to other patient groups with comparable degrees of physical disability. The present review (a) examines specific methodological issues associated with research in this area, (b) describes the range and severity of emotional disorders in MS and PD, and (c) examines both endogenous and reactive explanations to account for the increased prevalence of emotional dysfunction in these two disorders. Suggestions for future research are offered, as well as implications for treatment.

Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis.

The authors examined whether specific neuropsychological abnormalities in multiple sclerosis (MS) are associated with focal lesion areas detected by MRI. Lesion area, regardless of distribution, correlated with performance on the vast majority of neuropsychological procedures. No significant difference appeared between groups with normal/mild and moderate overall cognitive impairment on any of the MRI measures. However, patients with severe cognitive impairment had greater lesion area, regardless of location, and had significant atrophy of the corpus callosum compared with the other two groups. These results suggest that severe atrophy of the corpus callosum reflects global disease and provides a relatively focal morphological marker of severe cognitive impairment in MS.

The role of the caudate in nonmotor behaviors in Huntington's disease.

Neuropsychologic data suggest an important role for the caudate nucleus (CN) in behavioral impairments in Huntington's disease (HD). These include abnormalities in executive function, egocentric visuospatial representations, communication, and retrieval of declarative memories, changes in personality, and psychiatric disturbances. Animal paradigms of CN lesions support a role for the CN in some of these behaviors. Current theories of basal ganglia function add explanatory value to the role of the CN in these behaviors. A disconnection of the caudate from limbic structures, including the amygdala may account for many nonmotor behaviors observed in HD.

Magnetic resonance imaging in Parkinson's disease.

Magnetic resonance imaging was utilized to examine changes in the pars compacta associated with Parkinson's disease. We found a reduction in average width of the pars compacta in advanced- but not early-stage patients. Conversely, a significant difference in width (right minus left) was observed in early- but not late-stage patients. Width asymmetry may be a sensitive magnetic resonance imaging indicator for the early detection of Parkinson's disease when there is a predominance of unilateral clinical symptoms.

The pattern of depressive symptoms varies with progression of Parkinson's disease.

Whether or not depressive symptoms increase in severity with progression of Parkinson's disease (PD) remains uncertain. Unlike previous studies, we examined whether the severity of specific features of depression (mood, self reproach, vegetative, and somatic symptoms) differ with respect to the progression of PD. Results indicated that symptoms related to both mood and self-reproach were present in the early stages of PD but did not increase in severity with advancing disease. Somatic features of depression were evident early and increased with disease progression, and vegetative symptoms were seen only in the later stages of PD. The different patterns of these depressive features with progression of PD may account in part for the variations seen in previous studies.

A brief scale for the dementia of Parkinson's disease.

The lack of standardized criteria and methodologies to assess dementia in patients with Parkinson's disease has resulted in inconsistencies and controversies in the literature regarding the incidence and basis of this condition. The authors examined a large group of patients with Parkinson's disease using two standardized sets of criteria for dementia. The neuropsychological data obtained was analyzed using stepwise discriminant analysis, and a brief scale was developed. The results indicated that a regression equation derived from just three neuropsychological procedures (which take only 10 minutes to administer) provides maximum discrimination between patients originally classified as demented or non-demented according to standardized criteria. Cut-off values for the product of the regression equation were calculated to accurately and reliably classify patients using the brief scale.

Neuropsychological differences between the dementias of Alzheimer's and Parkinson's diseases.

The question of whether dementia of the Alzheimer type and dementia associated with Parkinson's disease are clinically separable is controversial. We examined possible neuropsychological differences in these two patient groups matched for overall severity of dementia. Patients with dementia of the Alzheimer type had more severe impairment on measurements of memory, language, and orientation, and, unlike patients with Parkinson's disease, there was evidence of apraxia. Patients with Parkinson's disease had more severe impairment related to speed of information processing, and, unlike patients with dementia of the Alzheimer type, they also had disturbance of mood. The nature of visuospatial abnormalities also differentiated the two groups. The pattern of neuropsychological differences is consistent with the cortical-subcortical hypothesis.

Magnetic resonance imaging in dementia of Parkinson's disease.

The possibility that dementia in Parkinson's disease is associated with specific cerebral abnormalities identifiable by magnetic resonance imaging (MRI) was examined. Sixty eight patients with Parkinson's disease and 28 age and education matched normal controls were evaluated using neuropsychological procedures that included assessment of language, memory, cognition, visuospatial skills and mood. Twenty three patients (34%) were found to have developed significant impairment in at least three of the five areas, thus meeting criteria for a dementia syndrome. Eleven patients (16%) had no intellectual impairment and thirty four patients (50%) had a mild to moderate intellectual disturbance. Patients with (n = 10) and without dementia (n = 20), matched for severity of Parkinson's disease, and normal controls (n = 10) matched for age with the two patients groups, were evaluated by MRI. MRI scans were analysed for evidence of generalised cerebral atrophy, ventricular enlargement, visualisation of the substantia nigra and severity of focal brain lesions. Results indicated that the presence of dementia in patients with Parkinson's disease was not associated with any specific pattern of MRI abnormalities.

Neuropsychological similarities in lateralized parkinsonism.

Parkinson's disease (PD) patients who have left or right predominance of motor symptoms may exhibit cognitive differences. Previous research found greater neuropsychological impairment in patients with both right and left motor predominance, and some found no differences. Variability in overall severity of disease among the patients studied makes evaluation of these reports difficult. We examined the possibility that neuropsychological differences may occur in different stages of disease by comparing patients with mild unilateral disease (Exp. 1) and advanced disease (Exp. 2). Results indicated that while overall cognitive impairment increased with advancing disease, the pattern of neuropsychological impairments were not different with respect to laterality of motor symptoms in either experiment.