Benign type of central pontine myelinolysis in alcoholism

Nine alcoholic patients with central pontine myelinolysis (CPM),who showed a favorable prognosis, are reported. The majority of them had taken part in binge drinking and had a subsequent consciousness disturbance for 18.1±10.9 (mean±SD) days. None of the patients had had acute correction of hyponatremia. Truncal ataxia and gait instability were present in most of the patients after recovery from the disturbance of consciousness. Most of them eventually gained independence, and magnetic resonance imaging showed that their pontine lesions tended to shrink. Electrophysiological studies detected prolonged latency between the I and III waves in auditory brainstem responses and between N11 and P13/14 onsets in the somatosensory evoked potentials. These clinical, radiological and electrophysiological findings should be of use in diagnosing CPM.     

Dietary docosahexaenoic acid protects against N-methyl-N-nitrosourea-induced retinal degeneration in rats

The effect of dietary intake of specific types of fatty acids on retinal degeneration due to N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis was evaluated. Fifty-day-old female Sprague-Dawley rats were given a single intraperitoneal injection of 50 mg kg(-1) body weight of MNU, and were then switched to one of five different diets containing the following fatty acids at the following weight percentages: 10% linoleic acid (LA); 9.5% palmitic acid (PA) and 0.5% LA; 9.5% eicosapentaenoic acid (EPA) and 0.5% LA; 4.75% EPA, 4.75% docosahexaenoic acid (DHA) and 0.5% LA; or 9.5% DHA and 0.5% LA. When rats developed MNU-induced mammary tumors with a diameter of > or =1 cm, or at the termination of the experiment (20 weeks after MNU injection), retinal tissue samples were obtained and examined. Incidence and severity of retinal damage were compared by histologic examination. MNU-induced retinal degeneration was prevented in rats fed the diet containing 9.5% DHA (4.75% DHA was less effective), whereas it was accelerated in rats fed the 10% LA diet. Over the course of the 20-week experimental period, the fatty acid composition of serum reflected differences in dietary fatty acids. The present results indicate that a diet containing 9.5% DHA can counteract MNU retinotoxicity in the rat retina. DHA may play a role in protection against MNU-induced photoreceptor cell apoptosis in the rat retina.     

Protein restriction diet in the predialysis period does not decrease survival of uremic patients after the introduction of hemodialysis therapy

To clarify whether a protein restriction diet in the pre-dialysis period affects the overall prognosis after initiating hemodialysis therapy, we compared the survival between patients with and without a protein restriction diet. Among 310 patients in whom hemodialysis was introduced between 1997 and 2000 at Toride Kyodo General Hospital, two hundred and ten patients were excluded due to an insufficient observation period (< 6 months) or the lack of records estimating their protein intake. One hundred patients were finally included in this study. All of these patients were followed at the hospital with their estimated protein intake using repeated (three times or more) urea nitrogen appearance in 24-hour collected urine samples over 6 months period to the initiation of dialysis therapy. The patients were divided into a protein restriction diet group (PRD 61 cases) and non-restriction diet group (NRD 39 cases), according to their estimated protein intake less or above 0.7 g/kg/day. Among the patient profile items, gender, cause of renal failure, and serum albumin did not differ between the two groups, but the age was higher in NRD (p < 0.01). Nineteen patients (PRD 8, NRD 11 cases) died during the observation period (0-65 months). On the analysis of their survival, PRD showed a better survival ratio by the Kaplan-Meier method (p < 0.01). Among the variables examined by Cox's proportional hazard test, age, PRD, and their combination showed significant risk ratios (1.06, 0.30, and 0.39 respectively) on survival after the initiation of hemodialysis. Hence a protein restriction diet in the pre-dialysis period does not deteriorate the prognosis even after the initiation of hemodialysis therapy.     

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104

BACKGROUND: Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS: One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS: Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS: Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study.     

Antiserum-mediated demyelination: Relationship between remyelination and functional recovery

A focal demyelinative lesion of peripheral nerve was produced by intraneural injection of either antiserum from rabbits with experimental allergic neuritis or experimental allergic encephalomyelitis or antiserum to galactocerebroside. We studied the relationship between clinical and electrophysiological recovery from this lesion and the morphological pattern of remyelination. Foot muscles on the injected side weakened within an hour of injection and remained paralyzed for 7 days; strength gradually returned to normal by 16 days after injection. Electrophysiological conduction block, apparent within a few hours of injection, persisted for about 7 days. At 8 days we detected dispersed, very low amplitude muscle action potentials with long latency. Morphologically, demyelinated axons were surrounded by Schwann cells at 7 days after injection, but compacted myelin was not present. After 8 days, remyelinating axons became surrounded by thickening compacted myelin. The time of onset of remyelination and the rate of remyelination up to 14 days following the injection were independent of axon size. The onset of clinical and electrophysiological recovery from the lesion corresponded to the appearance of 2 to 8 myelin lamellae around each remyelinating axon. At 37 days after injection, when conduction velocities had returned to preinjection values, myelin thickness of remyelinating fibers had increased to approximately one-third that of control nerves.     

Problems of subject inclusion in psychiatric research: observations from research with psychiatric inpatients.

In a recent study of psychiatric disturbance and decision making behaviour, it was observed that a significant number of psychiatric inpatients experienced difficulties in addressing themselves to the experimental tasks at hand. Despite the large number of studies that have used psychiatric inpatients as subjects, little, if any mention has been made of these difficulties. The following report describes the difficulties that have been observed in the above research project, and examines their possible implications for clinical assessment, research, and for clinical investigations and evaluation of treatment regimes (e.g. effectiveness of particular drug therapies), which use psychiatric inpatient populations as subject sources.     

Degeneration of the ipsilateral substantia nigra following cerebral infarction in the striatum.

BACKGROUND AND PURPOSE: In rats, degeneration of the ipsilateral substantia nigra occurs a few weeks after occlusion of the middle cerebral artery. The aim of this study was to clarify whether similar change is observed in stroke patients. METHODS: Eighteen patients with striatal infarction and six patients with cortical infarction in the territory of the middle cerebral artery were examined by means of sequential magnetic resonance imaging. RESULTS: In all patients with striatal infarction, T2-weighted images revealed a high-signal-intensity spot in the ipsilateral substantia nigra. Changes in the ipsilateral substantial nigra appeared at day 14 after stroke on average and then became less intense and smaller a few months after the stroke. By contrast, we observed no nigral changes in any patient with cortical infarction. CONCLUSIONS: The degenerative change in the ipsilateral substantia nigra initially found in the rat model similarly occurred in patients with striatal infarction. This remote change in the substantia nigra may represent magnetic resonance imaging detection of neuropathologic changes in this region through the striatonigral pathway.     

Immunocytochemical localization of tyrosine hydroxylase in rat adrenal medulla by the peroxidase labeled antibody method: effects of enzyme activation on ultrastructural distribution of the enzyme

A monospecific antibody against tyrosine hydroxylase (TH), purified from a transplantable rat pheochromocytoma, was produced in rabbits. Immunohistochemical techniques were employed in order to determine if a relationship exists between the subcellular distribution of TH and the level of activation of the enzyme in the rat adrenal medulla. Tyrosine hydroxylase activity in adrenals removed from non-stressed rats following pentobarbital anesthesia was found to be 12.9 +/- 1.0 nmol DOPA formed x mg protein-1. The use of ether anesthesia (17.9 +/- 2.0 nmol DOPA formed x mg protein-1), and the administration of electroconvulsive shock (ECS) followed by decapitation (35.9 +/- 2.0 nmol DOPA formed x mg protein-1) was associated with an acute activation of adrenal TH. The subcellular distribution of TH within the cytosol of chromaffin cells from animals subjected to anesthesia or ECS, as determined by immunocytochemical techniques, was similar. In all treatment groups chromaffin cells were found which had TH associated with some chromaffin granules. The percentage of chromaffin granules which appeared to contain TH was lower in animals subjected to ECS plus decapitation as compared with anesthetized animals. These observations suggest that the activation of adrenal medullary TH is not associated with a shift in the subcellular distribution of the enzyme from the cytosol to membranous structures.