A fully validated HPLC method for the simultaneous determination of acitretin and etretinate in plasma and its application to a pharmacokinetic study in healthy Korean subjects.

OBJECTIVE: Acitretin is used for the treatment of psoriasis. The purpose of this study was to validate an HPLC method for the determination of acitretin and etretinate and to investigate the pharmacokinetic characteristics of acitretin in healthy Korean subjects. MATERIALS AND METHODS: Plasma samples or calibrators were mixed with acetonitrile and retinyl acetate (internal standard). Butanol: acetonitrile (1:1 v/v) and K2HPO4 were added later. After vortexing, 30 microl of the supernatant was injected directly into the analytical column of an HPLC system. The samples were separated by C18 reversed phase HPLC and UV detection was performed at 350 nm. Various assay performances were evaluated. RESULTS: The linearity of acitretin and etretinate was adequate up to 500 ng/ml (R2 = 0.9937 for acitretin and R2 = 0.9923 for etretinate). The accuracy was 89.5 - 113.5% and the precision was satisfactory (within-run CV, 4.4 - 15.8%; between-run CV, 3.3 - 17.4%). The LLOQ was 2 ng/ml and the stability and specificity were satisfactory. However, after storage at room temperature for 24 h under light exposure, the concentrations of acitretin and etretinate decreased by 26.0 - 66.5%. Extraction recovery was 75.1 - 91.5%. Nine healthy Korean subjects were evaluated to study the pharmacokinetics of acitretin. A single oral dose of 30 mg acitretin (Neotigason, Roche Pharmaceuticals) was given to all volunteers. The mean +/- SD pharmacokinetics of acitretin in Koreans were as follows: Cmax 148.7 +/- 93.0 ng/ml, tmax 3.2 +/- 1.3 h, t1/2 81.2 +/- 26.5 h, and AUClast 2641.9 +/- 1274.8 ng h/ml. CONCLUSION: A simple HPLC method for the simultaneous determination of acitretin and etretinate was validated, and the pharmacokinetic characteristics of acitretin in the Korean population were investigated.

Postinfectious vasculopathy with evolution to moyamoya syndrome.

BACKGROUND: Parainfectious vascular events are a known complication of bacterial meningitis, typically occurring within two weeks of disease onset. Delayed vascular complications are rare. We present a case of progressive vasculopathy following bacterial meningitis. CASE DESCRIPTION: A 20 year old woman developed progressive vasculopathy after successful treatment of pneumococcal meningitis. Within eight months of her infection, angiography revealed the appearance of moyamoya syndrome. Despite aggressive immunomodulation and anticoagulation, she had multiple strokes. Autopsy confirmed severe narrowing of proximal cerebral vasculature with absence of inflammation or atherosclerosis. CONCLUSIONS: The inflammation and subsequent postinfectious autoimmune response associated with meningitis can lead to a progressive vasculopathy and may represent a pathophysiologic mechanism for the arterial occlusions seen in moyamoya syndrome.

Outcome in severe pediatric Guillain-Barré syndrome after immunotherapy or supportive care.

We reviewed duration of illness in 26 children with severe pediatric Guillain-Barré syndrome (GBS) during two contiguous 8-year periods that represent a "non-treatment era" of supportive care alone or a "treatment era" of supportive care plus either plasma exchange or intravenous immunoglobulin intervention. Our findings of similar recovery times in each treatment group suggest that immunotherapy in severe pediatric GBS may be less effective than in adult GBS, or effective only when given to certain patients very early in the course of the illness.

Pathological correlates of extrapyramidal signs in Alzheimer's disease.

Extrapyramidal signs frequently accompany Alzheimer's disease (AD), but the pathological substrate remains unknown. Clinical and postmortem information from patients with AD, Parkinson's disease, or progressive supranuclear palsy and control subjects seen at a large tertiary medical center between 1989 and 1994 was examined. AD patients who had taken neuroleptics and AD brains that also contained Lewy bodies were excluded. The presence of extrapyramidal signs was determined using the Unified Parkinson's Disease Rating Scale. Sections of basal ganglia, subthalamic nucleus, and substantia nigra were examined for neurofibrillary tangles and neuropil threads and the nigra for neuronal numbers. Patients with AD (with or without extrapyramidal signs) did not show neuronal loss in the nigra compared to control subjects, while both Parkinson's disease and progressive supranuclear palsy brains showed marked depletion. The number of neurofibrillary tangles and neuropil threads was increased in AD (with or without extrapyramidal signs) nigra compared to control tissue, and also in progressive supranuclear palsy nigra, but not Parkinson's disease nigra. The numbers of nigral neurofibrillary tangles and neuropil threads were positively related to extrapyramidal signs in AD. There were no correlations between tangles and threads in the basal ganglia or subthalamic nucleus and extrapyramidal signs in AD. Thus, extrapyramidal signs in AD correlate best with tangle pathology in the nigra and do not require the concomitant presence of Lewy bodies.

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Alzheimer's disease.

Alzheimer's disease is the most important cause of dementia, but its cause remains unknown. Amyloid plays a dominant role in many current theories of the pathogenesis, although it is still not clear if its deposition is the trigger or the result of other processes causing cell death. An association between sporadic and familial late-onset Alzheimer's disease and polymorphisms of apolipoprotein E located on chromosome 19 suggests a new genetic model of this condition. Head trauma and substandard education have been consistently associated with increased risk, whereas the use of anti-inflammatory agents may reduce the risk of developing Alzheimer's disease. Functional imaging may have developed to the point of making an important contribution to our understanding of the neural networks impaired in Alzheimer's disease, but it has not yet provided a diagnostic marker. The limited benefit of tacrine as an approved form of treatment is still being defined, but no new therapies have emerged.