Drugs as reinforcers--collaborative opportunities in epidemiology and behavioral pharmacology: comment on Alessi,Roll, Reilly,and Johanson (2002)

Despite reliance on a relatively small sample, the study by S. M. Alessi, J. M. Roll, M. P. Reilly, and C.-E. Johanson (2002) yielded remarkably consistent results, indicating that drug preference can be switched using conditioning procedures. However, because the study included only adults with limited drug involvement, the findings need to be interpreted taking the nature of the sample into account. This limitation points to opportunities for collaboration between experimental and epidemiologic researchers. Specifically, nesting experimental studies within longitudinal epidemiologic studies would reduce the potential for bias in sample selection while providing experimental data that are usually not available in observational epidemiologic research.     

Nurses' use of alcohol and other drugs: findings from a national probability sample

This study examined the prevalence of alcohol and other drug (AOD) use among nurses in the 1984 National Longitudinal Survey of Youth (NLSY) using methods similar to those employed in a study comparing nurses and nonnurses from the 1980-1984 Epidemiological Catchment Area program (ECA). Conditional logistic regression was used to estimate the degree to which AOD use was associated with occupation. Results indicating that substance use is unrelated to occupation lend support to earlier findings from the ECA.     

PVAC (Corixa/Genesis/Medicis)

Corixa, Genesis and Medicis are developing PVAC, an immunomodulator derived from killed Mycobacterium vaccae and licensed from SR Pharma [309860], [312958], for the potential treatment of psoriasis [365490]. In February 2001, phase II trials were ongoing in the US, the Philippines and Brazil for the treatment of moderate-to-severe psoriasis [399066], [405985]. In January 2001, an NDA filing was expected to take place in 2003 [396733]. In January 2002, Medicis and Corixa planned to initiate another phase IIb trial [436398], and by June 2002, two studies in patients with mild-to-moderate plaque psoriasis had began in the US and New Zealand, with the former designed to investigate the use of PVAC in combination with ultraviolet B (UVB) light [453772], [456657], [456836].     

The relationship between extramotor ubiquitin-immunoreactive neuronal inclusions and dementia in motor neuron disease

Dementia is thought to be an uncommon complication of motor neuron disease (MND). In addition to the characteristic motor system degeneration, pathological studies of MND patients with dementia have demonstrated changes in extramotor cortex; ubiquitin-immunoreactive inclusions are present in neocortical layer II neurons and hippocampal dentate granule cells. To examine how specifically this pathology is associated with dementia in MND, we performed ubiquitin immunohistochemistry on sections of hippocampus, prefrontal and temporal neocortex from 29 cases of MND, 10 with dementia and 19 with no clinical history of cognitive impairment. All cases with dementia had numerous ubiquitin-positive inclusions in dentate granule cells, whereas involvement of the neocortex was more variable. Six (32%) of the nondemented cases had ubiquitin pathology, which was similar to the demented cases in its morphology and distribution but of slightly less severe degree. These findings demonstrate that, although ubiquitinated inclusions in extramotor cortex are a consistent finding in MND with dementia, they are also common in MND in the absence of documented cognitive abnormalities. Such cases may either represent a subclinical stage of pathology or indicate that cognitive dysfunction is an underrecognized complication of MND.     

Antiganglioside antibodies in multifocal acquired sensory and motor neuropathy

BACKGROUND: Multifocal acquired demyelinating sensory and motor neuropathies are considered autoimmune and responsive to immunotherapy. In the absence of demyelination, however, they are considered idiopathic if no other cause is found. OBJECTIVE: To determine whether patients with multifocal acquired sensory and motor neuropathy of an otherwise unknown cause have antiganglioside antibodies, regardless of whether they are classified as demyelinating or axonal, indicating a possible immune-mediated origin. PATIENTS AND METHODS: Serum samples from 25 patients with multifocal acquired sensory and motor neuropathy of an otherwise unknown cause were tested for antibodies to gangliosides using an agglutination immunoassay. Reactive serum samples were further tested by enzyme-linked immunosorbent assay against individual gangliosides. Electrophysiologic studies were reviewed for evidence of demyelination. RESULTS: Increased levels of ganglioside antibodies were detected in 12 (48%) of the 25 patients using the agglutination immunoassay, and in 7 (58%) of the 12 agglutination-positive patients by the enzyme-linked immunosorbent assay. Serum samples from these 7 patients had IgG antibodies to 1 or more gangliosides; none had elevated levels of IgM antiganglioside antibodies. Three of the patients fulfilled 2 of the American Academy of Neurology electrophysiologic criteria for demyelination, but none fulfilled the 3 of the 4 possible criteria required for the diagnosis of demyelinating neuropathy. A sural nerve biopsy specimen in 2 patients revealed axonal degeneration. CONCLUSION: Multifocal sensory and motor neuropathies of an otherwise unknown cause may be associated with antiganglioside antibodies, regardless of whether they exhibit demyelinating features.     

Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia

BACKGROUND: Progressive brain atrophy is associated with Alzheimer disease (AD) and other dementias. Regional differences in brain atrophy may reflect clinical features of disease. OBJECTIVE: To identify regions of cerebral atrophy that are associated with AD vs other dementias. SETTING: University hospital dementia clinic. PARTICIPANTS: Eleven patients with AD and 11 with semantic dementia (SD), matched for age, sex, education, and degree of overall cognitive impairment and 15 normal controls. METHODS: Voxel-based morphometry was used to compare patterns of gray matter loss, measured on T1-weighted magnetic resonance images, between patients with AD or SD, a subtype of frontotemporal lobar degeneration, and controls. Statistically significant differences in regional gray matter concentration, after multiple-comparisons correction, between groups of subjects were identified. RESULTS: Patients with AD were more impaired than those with SD on tests of visuospatial function and on simple calculations. Consistent with these neuropsychological deficits, the most significant area of atrophy in the AD group was the left parietal cortex vs controls (z = 5.0; P =.04). Compared with SD, AD was associated with more atrophy in the left parietal lobe (z = 5.6; P =.04) and bilaterally in the posterior cingulate/precuneus (z = 5.1; P =.04). A discriminant function analysis demonstrated that the degree of atrophy of right posterior cingulate, left parietal lobe, right amygdala, and right anterior temporal lobe structures correctly classified 96% of the patients. CONCLUSION: Alzheimer disease is associated with a specific pattern of cortical atrophy compared with SD.     

Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy

BACKGROUND: Current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are research oriented favoring specificity over sensitivity. Application of such criteria in clinical practice may miss the diagnosis in potentially treatable patients. OBJECTIVES: To analyze the electrophysiologic abnormalities in a cohort of patients with clinically defined CIDP, to compare these data with published electrodiagnostic criteria, and to identify a set of abnormalities that is shared by all patients with CIDP. DESIGN: Retrospective medical record review. SETTING: Academically based neuromuscular clinic.Patients Fifteen patients with clinically diagnosed relapsing sensorimotor CIDP. INTERVENTIONS: Administration of intravenous immunoglobulin or prednisone. MAIN OUTCOME MEASURES: Electrodiagnostic studies. RESULTS: All patients had electrodiagnostic abnormalities in at least 3 nerves with possible partial conduction block or demyelinating range abnormalities in at least 1 nerve. The diagnostic sensitivities of 5 published CIDP criteria were as follows: the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (40%), Saperstein et al (47%), Nicolas et al (53%), Hughes et al for the Inflammatory Neuropathy Cause and Treatment Group (60%), and Thaisetthawatkul et al (70%). CONCLUSIONS: Current electrodiagnostic criteria for CIDP are insensitive and may fail to diagnose the condition in a substantial number of patients. More inclusive criteria that allow identification of patients in routine clinical practice are needed.