Early diffusion MR imaging findings and short-term outcome in comatose patients with hypoglycemia.

BACKGROUND AND PURPOSE: The relationship between the MR imaging features and clinical outcomes in patients with hypoglycemic encephalopathy has always been evaluated retrospectively. The aim of this study was to prospectively evaluate whether MR imaging features of patients presenting with hypoglycemic coma are predictive of short-term (1-week) outcomes. MATERIALS AND METHODS: Subjects were 36 consecutive patients with hypoglycemia who were in a comatose state on arrival at our hospital from April 2006 to March 2010. MR imaging findings on arrival in relation to the patients' clinical course after glucose infusion were evaluated. RESULTS: Thirteen of the 36 patients showed no MR imaging abnormalities on arrival. DWI revealed focal lesions involving the internal capsule in 13 patients and lesions involving bilateral hemispheric white matter in 10 patients. After glucose administration, the patients without lesions and patients with focal internal capsule lesions recovered completely within 1 day. However, patients with diffuse white matter lesions did not recover even within 1 week despite glucose administration. There was no statistical difference in the initial blood glucose levels among patients with the various types of MR imaging findings. CONCLUSIONS: On early MR imaging, hypoglycemic brain injury may first appear in the internal capsule and then spread into the hemispheric white matter. The absence of a lesion or the presence of a focal internal capsule lesion may suggest a good outcome. However, diffuse hemispheric white matter lesions may indicate a poor 1-week outcome.

Positional nystagmus in patients with chronic dizziness.

BACKGROUND: In elderly people, chronic dizziness is endemic. However, chronic dizziness of unknown origin is difficult to assess. OBJECTIVE: To investigate whether mild unrecognised benign paroxysmal positional vertigo (BPPV) is a cause of isolated chronic dizziness in the elderly. PATIENTS AND METHODS: The prevalence of extremely weak, horizontal, direction changing apogeotropic positional nystagmus (HAPN) that had not been detected by conventional examination was evaluated in 200 patients with isolated chronic dizziness and in 155 age matched control subjects without dizziness. RESULTS: A high prevalence of weak HAPN was found in patients with isolated chronic dizziness (98/200 (49.0%)) compared with the prevalence in control subjects without dizziness (25/155 (16.1%); p<0.0001). Symptoms improved in some patients by daily positional exercise for BPPV. CONCLUSION: Because BPPV is the most common cause of dizziness in the elderly, and HAPN is a characteristic of horizontal canal BPPV, our findings suggest that mild persistent BPPV is a possible cause of chronic dizziness of otherwise unknown origin in the elderly.

Staged in vitro reconstitution and implantation of engineered rat kidney tissue.

A major hurdle for current xenogenic-based and other approaches aimed at engineering kidney tissues is reproducing the complex three-dimensional structure of the kidney. Here, a stepwise, in vitro method of engineering rat kidney-like tissue capable of being implanted is described. Based on the fact that the stages of kidney development are separable into in vitro modules, an approach was devised that sequentially induces an epithelial tubule (the Wolffian duct) to undergo in vitro budding, followed by branching of a single isolated bud and its recombination with metanephric mesenchyme. Implantation of the recombined tissue results in apparent early vascularization. Thus, in principle, an unbranched epithelial tubular structure (potentially constructed from cultured cells) can be induced to form kidney tissue such that this in vitro engineered tissue is capable of being implanted in host rats and developing glomeruli with evidence of early vascularization. Optimization studies (of growth factor and matrix) indicate multiple suitable combinations and suggest both a most robust and a minimal system. A whole-genome microarray analysis suggested that recombined tissue recapitulated gene expression changes that occur in vivo during later stages of kidney development, and a functional assay demonstrated that the recombined tissue was capable of transport characteristic of the differentiating nephron. The approach includes several points where tissue can be propagated. The data also show how functional, 3D kidney tissue can assemble by means of interactions of independent modules separable in vitro, potentially facilitating systems-level analyses of kidney development.

Morphological analysis of leucocyte transmigration in the pleural cavity.

The role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide-stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno-scanning electron microscopy (immuno-SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno-SEM showed that the expression of intercellular adhesion molecule-1 (ICAM-1) on the parietal pleural mesothelial cells was significantly up-regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule-1 (VCAM-1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen-1 (LFA-1), macrophage-1 molecule (Mac-1) and very late appearing antigen-4 (VLA-4), all ligands of ICAM-1 and VCAM-1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.

Spatial distribution of cell adhesion molecules on the peritoneal surface in the cecal perforation-induced peritonitis.

For understanding the immunological functions of the peritoneum, spatial localization of integrins and their ligands was studied by immuno-SEM on the peritoneal surface of mice with cecal perforation-induced peritonitis. The cecal peritoneum 24 hr after perforation was stained with specific antibodies against LFA-1, Mac-1, VLA-4, ICAM-1, VCAM-1, and fibronectin diluted with cold University of Wisconsin (UW) solution in conjunction with immuno-gold labeling. The spatial localization of those cell adhesion molecules was detected by backscatter electron (BSE) imaging with field emission scanning electron microscope (FESEM). Numerous leukocytes with diverse surface ultrastructure were observed on the peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial cells, and others adhered to the exposed underlying connective tissue. The BSE imaging showed the ubiquitous distribution of Mac-1 on all membrane domains of leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant expressions of LFA-1 and VLA-4 were discernible on ruffles/microvilli of some leukocytes. The mesothelial cells remaining in the inflamed area expressed both ICAM-1 and VCAM-1 on their microvilli. The fibronectin was detected on presumable collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on fibrin extending between leukocyte aggregation. The spatial microlocalization of integrins was clarified on the leukocytes emigrated in peritonitis, and their ligands were detected on the inflamed peritoneum.

Three-dimensional morphological analysis of antigen-antibody reaction in hepatic sinusoids preserved in hypothermic UW solution.

ICAM-1 antigen-antibody reaction was visualized by three-dimensional immunoscanning electron microscopy of hepatic sinusoids in rat liver treated with hypothermic University of Wisconsin (UW) organ preservation solution. The results were compared with similar antigen-antibody reactions carried out with immunoliposomes injected in vivo. Morphologically, the hepatic sinusoids were preserved well during the hypothermic procedure. Endothelial cells had a large number of fenestrations, which partly aggregated and formed sieve plates. ICAM-1 expression was induced by injection of LPS and detected by monoclonal antibody in the UW solution followed by gold-labeled secondary antibody. ICAM-1 was restricted mostly to the unique areas of sieve plates with immature, small fenestrations. A similar distribution of ICAM-1 was present when detected by in vivo injection of immunoliposomes containing the monoclonal ICAM-1 antibody. The results showed that antigen-antibody reactions can take place in livers preserved in hypothermic UW solution. Further, the reaction is similar to that which could occur in vivo during transplantation. This suggests that it may be possible to block potentially harmful antigen-antibody reactions by addition of appropriate antibodies to hypothermic UW solution prior to transplantation.

[Bilateral ptosis, bilateral upgaze and adduction paresis, and monocular downgaze paresis from a mesencephalic infarction].

We report a 57-year-old man with an ischemic lesion in the midbrain. In the acute stage, he presented with bilateral ptosis and markedly limited extraocular motion except for bilateral abduction and downward motion of the right eye. The pupillary reaction to light of his left eye also was impaired. He was admitted to our hospital, and brain MRI showed a small infarction extending from the left paramedian to the median tegmentum of the midbrain. Three weeks after admission, the ptosis and limited extraocular right eye motion had resolved. The pupillary reaction and downward motion of the left eye normalized gradually within 3 weeks. Two months after admission, ptosis and the limited left eye adduction were partially resolved, but the markedly limited upgaze of the left eye had not changed. Initial neuro-ophthalmologic findings suggested involvement of the caudal part of the oculomotor nucleus and the left oculomotor nerve within the midbrain. The pattern of neuro-ophthalmologic impairment seen in our patient led us to conclude that the caudal oculomotor nucleus and medial part of the fascicular fibers of the left oculomotor nerve probably recovered first, after which recovery of the fascicular fibers progressed laterally. The results of serial MRI were consistent with this interpretation.

Eye deviation in patients with one-and-a-half syndrome.

To understand malalignments of the visual axes in one-and-a-half syndrome, we measured eye positions in 4 patients with this syndrome under two conditions: with Frenzel goggles to prevent eye fixation and without Frenzel goggles. When fixation was prevented with the Frenzel goggles, all patients showed mild outward deviation in both eyes. Removal of the Frenzel goggles elicited adduction of the eye ipsilateral to the side of the lesion for fixation, with greater outward deviation of the contralateral eye (acute stage), or adduction of both eyes to midposition for biocular fixation (convalescent stage). In 3 patients whose outward eye deviation with Frenzel goggles was greater on the ipsilateral side, a transition from one-and-a-half syndrome to ipsilateral internuclear ophthalmoplegia was noted, whereas a transition to ipsilateral gaze palsy was seen in the one patient whose deviation was greater on the contralateral side. These findings suggest that in one-and-a-half syndrome patients, the eyes tend to be in divergent positions when fixation is prevented; ipsilateral eye deviation may result from medial longitudinal fasciculus involvement, and contralateral eye deviation may result from paramedian pontine reticular formation involvement. Viewing a target may lead to a secondary deviation or adaptation of eye positions for fixation.

[Radiculopathy and reversible axonopathy in a tetraplegic patient with meningeal carcinomatosis].

We report a 49-year-old tetraplegic woman with meningeal carcinomatosis secondary to breast cancer. Serial nerve conduction studies in the extremities revealed that the amplitudes of the sensory nerve action potentials (SNAP) and the compound muscle action potentials (CMAP) decreased rapidly within a few days after her admission. Plasma exchanges were done four times and restored the SNAP amplitudes to normal range. The CMAP amplitudes were also increased, but not to the normal range. These electrophysiologic changes were not associated with clinical improvement. Our patient's tetraplegia may be associated with a combination of two different mechanisms; reversible axonopathy caused by humoral factors that can be removed by plasma exchange, and irreversible radiculopathy due to direct cancer cell invasion.

Peroxisomes in permanent and provisional kidneys. Phylogenic and ontogenic considerations.

Peroxisomes in three forms of vertebrate kidney (pronephros, mesonephros, and metanephros), as permanent or provisional kidney, are summarized concerning their ultrastructure and developmental changes. Because the peroxisome is known to be diverse in mammalian metanephros, and species difference is its distinctive feature among cell organelles, information should be obtained on each kidney of each species. The ultrastructural and biochemical features of peroxisomes have at least been partly delineated in the metanephros and mesonephros, but nothing is known about the pronephros. Ultrastructural studies of the metanephric peroxisomes are present in mammals, birds, and reptiles, but information on their development is restricted to mammals and birds. As for the mesonephric peroxisomes, both ultrastructural and developmental data have been accumulating on mammals and amphibians, and ultrastructural information is present on fishes, but not on birds and reptiles. At present, studies on peroxisomes of provisional kidney have been restricted to mammalian mesonephros. The common features of renal peroxisomes previously examined are that they are spherical cell organelles with a single limiting membrane in ultrastructure, and are positive for catalase. Information on the ultrastructure and enzymes is not sufficient at present for comparing the ontogenesis of renal peroxisomes with their phylogenesis.

[Chronic sensory ataxic neuropathy associated with IgM antibody against b-series gangliosides including GD1b].

We described a 62-year-old man with a 10 years history of chronic sensory ataxic neuropathy. His laboratory investigations revealed elevated serum IgM with IgM kappa paraproteinemia, IgM antibody against b-series gangliosides including GD3, GD2, GD1b, GT1b, GQ1b, GQ1b alpha, and high titer of cold agglutinin. The clinical and serological features in our patient were compatible with the diagnosis of CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M-protein, agglutination, and disialosyl antibodies), proposed by Willison et al. IgM antibody against b-series gangliosides including GD1b appeared to play an essential role in developing autoimmune sensory ataxic neuropathy.

Encephalopathy in scleromyxedema.

The authors monitored CSF findings for over 5 months in a patient with a fatal case of scleromyxedema and two episodes of encephalopathy. During both encephalopathy episodes, CSF protein and immunoglobulin G (IgG) levels were elevated without an increased IgG index or IgG synthesis rate. A CSF-dominant increase in the concentration of interleukin-6 (IL-6) also was noted during encephalopathy. These findings suggest a disruption of the blood-brain barrier and that IL-6 may play some role in mediating the encephalopathy. OFF

Quantification of protein A-gold staining for peroxisomal enzymes by confocal laser scanning microscopy.

The protein A-gold technique has been widely applied for visual localization and quantification of various antigens by electron microscopy. Observation of specimens stained by the protein A-gold technique with conventional light microscopy is difficult because of insufficient sensitivity of the staining. Light microscopic visualization and quantification of the reaction products were attempted employing a confocal laser scanning microscope (CLSM). Liver tissues of normal and peroxisome proliferator-treated rats were fixed and embedded in Lowicryl K4M resin. Ultrathin and thin sections were stained for catalase and a peroxisome-specific beta-oxidation enzyme by the protein A-gold technique. Ultrathin sections were observed by electron microscopy and the labeling density for each enzyme was analyzed with an image analyzer. Thin sections were observed with a CLSM in the reflection mode and the intensity of the light reflection was analyzed under the same conditions for all specimens. A comparison of these two observation procedures was also attempted using liver tissues stained with various concentrations of the antibody for catalase. The intensity of the reflection for each, as observed by CLSM, correlated well with the labeling density observed by electron microscopy. CLSM made it possible to quantify and to directly observe protein A-gold staining at the light microscopic level.(J Histochem Cytochem 47:1343-1349, 1999)