Behavioral neurology of multi-infarct dementia

Multi-infarct dementia (MID) is a heterogeneous entity in which a variety of cerebrovascular disorders leads to intellectual impairment. A variety of patterns of behavioral changes may be observed in MID, depression, psychosis, and personality change are common. The neurobehavioral syndromes of MID are determined by the specific arteries involved and the location and extent of tissue infarction.     

Passenger seating position and the risk of passenger death in traffic crashes: a matched cohort study

OBJECTIVE: To estimate the association of passenger seating position with the risk of death for passengers in traffic crashes. Design, setting, PARTICIPANTS: Matched cohort analysis of data from the National Highway Traffic Safety Administration Fatality Analysis Reporting System regarding 56 644 passengers in 23 308 passenger cars, light trucks, vans, and sport utility vehicles that crashed during 1990-2001. MAIN OUTCOME MEASURE: The adjusted risk ratio (aRR) for death of a rear seat passenger compared with a front seat passenger within 30 days of a crash. RESULTS: The aRR for all passengers in the rear seat in a crash was 0.79 (95% CI 0.77 to 0.82). This estimate varied by age, restraint use, and the presence of a front passenger airbag (p<0.001). For restrained passengers in cars with a front passenger airbag, the aRR was 0.62 (95% CI 0.48 to 0.81) for children 0-12 years, 0.96 (95% CI 0.88 to 1.06) for passengers 13-29 years, 1.03 (95% CI 0.93 to 1.15) for passengers 30-59 years, and 1.06 (95% CI 0.90 to 1.26) for passengers 60 years or older. The rear seat was associated with more protection in cars without front airbags and more protection for unrestrained passengers compared with restrained passengers. CONCLUSIONS: Previous studies have reported that the rear seat was safer for persons of all ages; thus seating a young child in the rear has often meant that older children and adults had to assume an increased risk of death by sitting in the front. These results suggest that when front passenger airbags are present and passengers are restrained, putting adults in front and children in back enhances child safety without sacrificing adult safety.     

Fracture-dislocation of the lunotriquetral coalition.

Bony fusions involving the carpus have a much higher prevalence in blacks relative to whites. This article describes a case of lunotriquetral coalition fracture-dislocation in an African American. This lesion is best treated through open reduction and pin fixation.     

Ketoconazole Impairs Early Pregnancy and the Decidual Cell Response via Alterations in Ovarian Function

Ketoconazole (KCZ) is an imidazole antifungal agent that alsoaffects P450 enzymes of the mammalian steroidogenic system.Several steps in the ovarian steroidogenesis pathway are knownto be inhibited by KCZ, but previous work has failed to addressthe ramifications of such inhibition with respect to early pregnancy.In initial studies, Holtzman rats (8–10/group) were administered10–100 mg/kg KCZ during days 1–8 of pregnancy. Onday 9, evaluations revealed a reduction at both 75 and 100 mgKCZ/kg in the number of implantation sites and serum progesteronelevels as well as an increase in ovarian weight The decidualcell response (DCR) was blocked by KCZ in parallel with decreasedserum progesterone and increased ovarian weight, indicatingdirect interference with uterine function. KCZ had no effectwhen given to long-term-ovariectomized rats that were hormonesupplemented to permit the DCR, indicating that the ovary wasat least one site of KCZ action on early pregnancy. Measurementof ovarian progesterone production in vitro from ovaries removedfrom rats treated in vivo with KCZ indicated a decline in progesteroneproduction, suggesting a direct effect of KCZ on ovarian steroidogenesis.These data demonstrate that KCZ can compromise early pregnancyand appears to do so by inhibiting progesterone synthesis inthe ovary.     

Depression and Parkinson's disease: a review.

OBJECTIVE: The purpose of this review is to provide an update of the research regarding depression in Parkinson's disease and to synthesize the information into a neurobiological model relating the structural and biochemical changes in this disorder to the behavioral manifestations. METHOD: The author used a computer-based search of the literature, augmented by extensive bibliography-guided article reviews, to find information on depression and Parkinson's disease. FINDINGS: Depression occurs in approximately 40% of patients with Parkinson's disease; depression in Parkinson's disease is distinguished from other depressive disorders by greater anxiety and less self-punitive ideation. Lower CSF levels of 5-hydroxyindoleacetic acid, a past history of depression, and greater functional disability are associated with a greater risk of depression in Parkinson's disease. Female gender, early age at onset of Parkinson's disease, and greater left brain involvement may also be risk factors. Approximately half of depressed patients with Parkinson's disease meet criteria for major depressive episodes; half have dysthymia. Depression is more common in Parkinson's disease with prominent bradykinesia and gait instability than in tremor-dominant syndromes. Depressed patients with Parkinson's disease have greater frontal lobe dysfunction and greater involvement of dopaminergic and noradrenergic systems than nondepressed patients with the disease. Mood changes in Parkinson's disease respond to treatment with conventional tricyclic antidepressants or ECT. CONCLUSIONS: Neurobiological investigations suggest that depression in Parkinson's disease may be mediated by dysfunction in mesocortical/prefrontal reward, motivational, and stress-response systems. Neuropsychological, metabolic, clinical, pharmacological, and anatomical studies support the involvement of frontal dopaminergic projections in patients with Parkinson's disease and depression.     

Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.