Clevudine for chronic hepatitis B: antiviral response, predictors of response, and development of myopathy.

Clevudine has been approved for the treatment of chronic hepatitis B (CHB) in South Korea. However, its long-term antiviral effect and safety awaits more study. The aim of this study was to evaluate antiviral efficacy, predictors of virologic response, and development of myopathy after clevudine therapy for CHB. The study included 102 nucleoside naïve CHB patients who had received clevudine for more than 6 months with good compliance. The median duration of clevudine treatment was 53 weeks (range, 25-90 weeks). A retrospective analysis of data retrieved from medical records was performed. The cumulative rate of virologic response [hepatitis B virus (HBV) DNA level <2000 copies/mL] at 48 weeks of clevudine therapy was 81%, and cumulative rate of clevudine resistance was 11% at 60 weeks of treatment. Independent predictors of virologic response to clevudine therapy were hepatitis B e antigen (HBeAg) negativity and rapid decrease of viral load during the early phase of treatment. The clevudine-related myopathy developed in 3.9% of patients, and was reversible after discontinuation of clevudine. Clevudine showed a potent antiviral response, and its effect was higher in HBeAg-negative patients, with rapid viral load reduction after therapy. However, long-term therapy for more than 1 year resulted in the development of considerable resistance and myopathy. Therefore, we should consider alternative antiviral agents if clevudine resistance or clevudine-induced myopathy is developed in patients on clevudine for the treatment of CHB.

Mesencephalic hemorrhage--a report of 3 cases.

We studied three patients with spontaneous mesencephalic hemorrhages. All presented with some degree of impaired consciousness and abnormal ocular movements. One patient had a convergence-retraction nystagmus with a unilateral hemorrhage confined to the dorsal midbrain. Another patient showed left third nerve palsy due to a unilateral hemorrhage that involved ventral midbrain. The third patient revealed left internuclear ophthalmoplegia with ataxia due to a pinpoint hemorrhage in the tegmentum of the left midbrain. The patients survived and major neurologic deficits recovered, but abnormal ocular movements persisted.

Chronic progressive external ophthalmoplegia (CPEO) with 'ragged red fibers'--a case report.

Chronic progressive external ophthalmoplegia (CPEO) is a rare clinical syndrome characterized by slowly progressive paralysis of extraocular muscles. We report a male patient who had a 20 year history of CPEO. Histological examination of left deltoid muscle showed characteristic ragged red fibers. Electron microscopy revealed a number of abnormal mitochondria which contain paracrystalline inclusion bodies.

Assessment of regional cerebral blood flow (rCBF) in ischemic stroke using Tc-99m HMPAO SPECT--comparison with CT and MR findings.

To assess the regional cerebral blood flow (rCBF) in ischemic stroke, we analyzed the findings of single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (Tc-99m HMPAO). The SPECT images revealed abnormal areas of decreased perfusion in 29 out of 31 subjects (93.5%), which represented a higher detection rate than those for CT and MR (89.5%, respectively). Also, the areas of decreased perfusion were frequently larger than the lesions on CT and MR. Areas of decreased perfusion remote from the CT/MR lesions were found in 10 patients, including 8 with crossed cerebellar diaschisis (CCD). Thus, studies of rCBF by Tc-99m HMPAO SPECT can be useful in the assessment of ischemic stroke.

Alternating dissociated nystagmus with palatal myoclonus--a case report.

An extraordinary eye movement was seen in a vegetative patient. His eyeballs were exotropic in the primary position and showed dissociated nystagmus which appeared alternately in each eye every few seconds. He also had palatal myoclonus quite asynchronous with the nystagmus. To our knowledge, there has been no such nystagmus documented in the literature. We report the new nystagmus with his EOG and brain MRI.

MR imaging of the internal carotid artery in ischemic cerebrovascular disorders--clinical and angiographic correlation.

This study was intended to correlate the appearance of the cavernous segment of the carotid artery on MR images with the presence of significant stenosis or occlusion of the cervical carotid artery as seen on angiograms in 37 patients with cerebrovascular disorders who had brain MRI and arteriography. Three patients demonstrated an isointense signal within the carotid artery's cavernous segment, correlating with complete carotid occlusion as seen angiographically. Ten patients had variable signal intensity and/or luminal narrowing in the carotid siphon; seven of these findings correlated with angiographic evidence of carotid occlusion, while carotid branch occlusion was seen angiographically in the other three. The demonstration of normal signal void within a normal-appearing cavernous segment of the internal carotid artery in the remaining 24 patients correlated with an absence of significant stenosis within the cervical segment in 21 patients. In the remaining three, significant disease of the internal carotid artery was found. Isointensity or luminal irregularity within the intracranial carotid artery can indicate complete occlusion or slow flow. The presence of normal flow void in the intracranial segment does not exclude significant abnormality of the cervical segment of the carotid artery.

Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets.

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic pellagra encephalopathy combined with Wernicke disease.

Clinical and postmortem findings of a case that had combined alcoholic pellagra encephalopathy and Wernicke disease are described. This 51-year-old malnourished and chronic alcoholic man presented with progressive mental deterioration, pellagra dermatitis, hypertonus of the neck and other musculatures, myoclonic jerks with bizarre involuntary movements, in addition to total external ophthalmoplegia and gait disturbance. After administration of multivitamins, including thiamine and nicotinamide, these neurologic abnormalities were dramatically improved in a few days. However, the patient died thereafter because of sepsis associated with pneumonia. Postmortem examination revealed marked abnormalities in CNS, characterized by diffuse atrophy of gray matter and widespread neuronal degeneration and characteristic central chromatolysis in pontine nuclei, dentate nuclei, cranial nerve nuclei in the brain stem, Betz cells of the cerebral cortex, and Clarke's column and anterior horn cells of the spinal cord. There were also atrophy and gliosis of the mammillary bodies, degeneration and vascular proliferation of periaqueductal gray matter, and massive gliosis around the third ventricle. These neuropathological changes were compatible with symptoms of both alcoholic pellagra encephalopathy and Wernicke's disease, but they were also strongly suspected on clinical grounds.

Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis.

For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.