Mitochondrial encephalomyopathy (MELAS): pathological study and successful therapy with coenzyme Q10 and idebenone

Two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS) in one family are reported. Pathological examination of case 1 showed ragged-red fibers, with 7% of the fibers being unstained by cytochrome c oxidase stain, peripheral nerve damage, multiple areas of softening in the cerebrum and midbrain, and spongy changes in the cerebrum, optic nerve and pons. Electron microscopic examination revealed abnormal accumulations of mitochondria in the skeletal muscle, smooth muscle and cardiac muscle. The activity of cytochrome c oxidase in the brain and liver showed a tendency to decrease. In case 2 (maternal aunt of case 1), muscular weakness and peripheral nerve damage improved by treatment with coenzyme Q₁₀. By adding idebenone to the coenzyme Q₁₀ therapy, the EEG and Wechsler's Adult Intelligence Scale (WAIS) improved. Furthermore, in the cerebral spinal fluid (CSF), the protein, lactate, and pyruvate decreased, and the monoamines and monoamine metabolites increased.     

On the Psychophysiology of Dreaming: A Sensory Image ––– Free Association Hypothesis of the Dream Process

Abstract: A psychophysiological hypothesis of the dream process during REM sleep called "a sensory image-free association hypothesis" is proposed. It is assumed that a state with a sustained EEG pattern of drowsiness (non-REM stage-1) and muscle atonia produces a stream of disorganized and vague thinking as a background mentation during the REM sleep. The phasic excitation of the brain occurring concurrently with the burst of rapid eye movements (REMs) activates the hippocampal-neocortical memory system and draws out sensory images from the memory reservoir of the brain. The dreamer makes a freely organized association about the successive sensory images and makes up a dream story. This hypothesis is compatible not only with the recent neurophysiological findings but also with traditional psychological interpretation of the dream content.     

Endocrine Changes of the Hypothalamic, Pituitary and Adrenal Systems in Cyclic Vomiting

Children with cyclic vomiting had high blood ADH, ACTH, cortisol and plasma renin activity (PRA) during vomiting, and urinary excretion of 170HCS, 17KGS, 17KS, norepinephrine (NE), epinephrine (E), normetanephrine (NMN), metanephrine (MN) and vanillylmandelic acid (VMA) was increased. After disappearance of the vomiting, the levels fell to within the normal range. Variation was not observed in blood prolactin (PRL), Na, osmotic pressure or urine dopamine (DA). Normal findings were obtained in the intravenous water loading test, response of anterior pituitary hormones and cortisol to the insulin, TRH and LH-RH loading, the metopirone test and the dexamethasone suppression test which were performed 1 week after the vomiting.     

Impairment of Parietal Cortical Functions Associated with Episodic Prolonged Spike-and-Wave Discharges

A case of a 16-year-old girl who showed selective impairment of higher cortical functions and very slight lowering of initiative activity without overt disturbance of consciousness, during prolonged generalized spike-and-wave discharges with a parietal predominance, is reported. Neuropsychological investigations during the episode revealed a disturbance of parietal cortical functions, such as constructional apraxia, ideational or ideomotor apraxia, finger agnosia, acalculia, right-left disorientation, disturbance of visual-spatial orientation, and agraphia. The transient impairment of parietal cortical functions associated with the parietal-dominant spike-and-wave discharges was suggested as a principal pathophysiology of the clinical picture. Emphasis is placed on the importance of neurophysiological assessment in such a case.     

Biodistribution of Micelle-Forming Polymer–Drug Conjugates

Polymeric micelles have potential utility as drug carriers. To this end, polymeric micelles based on AB block copolymers of polyethylene oxide (PEG) and poly(aspartic acid) [p(Asp)] with covalently bound Adriamycin (ADR) were prepared. The micelle forming polymer–drug conjugates [PEO-p(Asp(ADR)] were radiolabeled and their biodistribution was investigated after intravenous injection in mice. Long circulation times in blood for some compositions of PEO-p[Asp(ADR)] conjugates were evident, which are usually atypical of colloidal drug carriers. This was attributed to the low interaction of the PEO corona region of the micelles with biocomponents (e.g., proteins, cells). Low uptake of the PEO-p(Asp(ADR)] conjugates in the liver and spleen was determined. The biodistribution of the PEO-p[Asp(ADR)] conjugates was apparently dependent on micelle stability; stable micelles could maintain circulation in blood, while unstable micelles readily formed free polymer chains which rapidly underwent renal excretion. Long circulation times in blood of PEO-p(Asp(ADR)] conjugates are thought to be prerequisite for enhanced uptake at target sites (e.g., tumors).     

ATHEROSCLEROSIS AND ENDOTHELIUM

A simple and highly reproducible culture method of aortic endothelial cells from cadaver is herein reported. Major bacterial contamination could be prevented by administration of an antibiotic cocktail consisting of gentatnicin, ampicillin, and amphotericin B. Endothelial cells from the thoracic aorta were viable up to 17 hours postmortem and successfully culturable from the aorta by dispase desquamation from the subendothelial substrate. The cultured cells varied in size and shape depending on the degree of individual atherosclerotic severity and could be divided into two major subtypes. The first type is a small and polygonal uniform cell (typical endothelial cell) and the second type is a mixture of spindle and giant bizarre cells often associated with multinuclei (variant endothelial cell). Both types of endothelial cells have characteristics specific for endothelium, such as factor VIII related surface antigen, Weibel-Palade body, and high productivity of prostacyclin.     

Parkinson's Disease: Distribution of Lewy Bodies in the Peripheral Autonomic Nervous System

This report concerns the presence and distribution of Lewy bodies in the peripheral nervous system of three patients with Parkinson's disease and ten age-matched nonparkinsonian individuals. We examined the paravertebral and celiac ganglia as representatives of the sympathetic system; the submandibular ganglion as representative of the parasympathetic system; the esophagus, stomach, duodenum, jejunum, ileum and colon as representatives of the enteric system, and the trigeminal and dorsal spinal ganglia as representatives of the somatic sensory system. Lewy bodies were observed in the peripheral sympathetic and enteric systems of two of the three patients with Parkinson's disease. These two patients had numerous Lewy bodies in the submandibular ganglia. The third patient did not have Lewy bodies in the peripheral autonomic nervous system, nor did the ten control individuals studied. Lewy bodies were not detected in the somatic sensory system of any of the three parkinsonian patients. Our findings indicate that the peripheral autonomic system, including the parasympathetic system is affected in Parkinson's disease.     

Endoscopic Clipping with a New Rotatable Clip-Device and a Long Clip

Abstract: We developed a rotatable, highly durable clipping device (rotatable clip-device) and a long clip which can be used to effectively grasp a large bite of tissue. However, application of the long clip required a special reinforced clipping device. The new rotatable clip-device can be appropriately used in combination with the long clip because of its improved strength and rotatability. The rotatable clip-device was used for endoscopic treatment of 133 patients, including 43 requiring hemostasis of gastrointestinal bleeding, 43 with prophylactic clipping following polypectomy, 39 with mucosal closure following endoscopic mucosal resection (EMR), and 10 undergoing prophylactic ligation of esophageal varices. The long clips were used mainly for mucosal closure after EMR. The rotatable clip-device was found to be especially useful for hemostasis of soft bleeding lesions. Prophylactic clipping following polypectomy prevented complications in 40 out of 41 patients. Mucosal closure by means of clipping following EMR prevented complications in all 39 patients, and the rotatability of the rotatable clip-device and the large bite capacity of the long clip greatly facilitated closing mucosal defects, especially large defects. In the 10 patients who underwent prophylactic clipping of esophageal varices, the rotatable clip-device allowed the varices to be grasped securely and ligated effectively. During endoscopic treatment, three of the four clip-devices functioned normally despite frequent auto-claving and clipping procedures.