Bioelectronic options for a totally implantable hearing device for partial and total hearing loss

A semi-implantable electromagnetic hearing device (SIMEHD) for sensorineural hearing loss has been developed and tested in animals and limited clinical trial. The authors' electromagnetic transducer, which is the driver of the SIMEHD, when used in reverse mode is applicable to the fabrication of a bioelectronic microphone. Instead of being a driver, it transforms the sound-activated eardrum-ossicular vibration into an electric signal through the NdFeBo magnet implanted on the head of the malleus, interacting in a contactless manner with the electromagnetic coil.     

Autoimmune hepatitis

Autoimmune hepatitis is one of the causes of chronic progressive liver disease in childhood. Here we report 14 cases with clinical findings, therapeutic management and prognosis, in order to define the course of the disease. Diagnosis of autoimmune hepatitis was done with the presence of at least one of these autoantibodies; antinuclear antibody, smooth muscle antibody, liver-kidney microsomal type 1 antibody, and perinuclear antineutrophilic cytoplasmic antibody. Patients were seen every 3 to 6 months. After doing a complete physical examination, biochemical parameters and autoantibodies determined at each visit. Mean age at diagnosis was 10.9±2.6 years (range, 7–15.5 years) and female to male ratio was 1∶3. Thirteen patients had jaundice and all had high levels of ALT, AST and gammaglobulin. Hepatomegaly was found in 71.4% and splenomegaly in 64.3% of the patients. All patients were classified as type 1 autoimmune hepatitis. Liver biopsies revealed severe active hepatitis with mononuclear cell infiltration in portal areas, piecemeal necrosis. Drug therapy consisted of prednisone (2 mg/kg/day) per oral at the beginning, and addition of azathioprine (1.5 mg/kg/day) per oral at the 3rd-6th month with slow tapering of prednisone in 12 children. Both drugs were started together to two patients. Follow-up period was 30.7±15.6 months (range, 12–72 months). Sustained normalization of ALT could not be obtained with tapering doses of prednisone alone. Decrease in ALT levels did not correlate with disappearance of serum autoantibodies. None of the patients showed decompensation of liver disease. Azathioprine administration is necessary to decrease prednisone dose and to maintain a sustained normal transaminase values.     

Serum matrix-degrading enzymes in rats intoxicated with selenium

The effect of poisoning doses of selenium on serum matrix-degrading enzymes activity was investigated in rats intoxicated with selenium. Fifteen animals were receiving orally sodium selenite in a daily dose of 300 microg/kg body weight. Intoxication with selenium was carried out for 10 weeks. The present study revealed significant increase in activities of enzymes involved in the connective tissue matrix metabolism i.e. beta-glucuronidase, N-acetyl-beta-glucosaminidase, elastase and collagen peptidase. There was no change in the cathepsin activity. The relative enzyme activities calculated over protein level resulted in higher values than those found in direct measurements. Serum enzyme activity was increased most for elastase (about 31%) and N-acetyl-beta-glucosaminidase (about 33%) based on activity per gram of protein. The current data indicate that lysosomes are target organelles for selenium toxicity. Generalized increase in lysosomal enzymes activity contributes to the altered metabolism of the connective tissue in selenium-intoxicated animals. The mechanisms that lead to the increase of lysosomal enzymes activity in rats receiving poisoning doses of selenium could be related to biochemical disturbances caused by selenium toxicity.     

Role of skin prick test and serological measurement of specific IgE in the diagnosis of occupational asthma resulting from exposure to vinyl sulphone reactive dyes

OBJECTIVES—Some patients with occupational asthma resulting from exposure to reactive dyes have skin reactivity to the causative dyes and specific IgE to reactive dyes have been found in these patients. However, the usefulness of skin prick tests (SPTs) and serological measurement of specific IgE in screening, diagnosis, and monitoring the occupational asthma resulting from exposure to reactive dyes have not yet been assessed. In this study, the clinical validation of SPTs and measurement of specific IgE to vinyl sulphone reactive dyes by enzyme linked immunosorbent assay (ELISA) was evaluated.
METHODS— 42 Patients with occupational asthma from reactive dyes (true positive group) were enrolled. In these the causative reactive dye was confirmed by bronchial challenge test. 93 Asymptomatic factory workers with negative challenge to the reactive dye (true negative group) and 16 unexposed controls with negative challenge to the reactive dye were also enrolled. Skin prick tests were done with 10 mg/ml reactive dye in 0.4% phenol/0.9% saline. IgE specific to reactive dye conjugated to human serum albumin (HSA) was measured with enzyme linked immunosorbent assays (ELISAs).
RESULTS—None of the unexposed controls had a positive response to SPTs. The sensitivity (76.2% v 53.7%), specificity (91.4% v 86.0%), positive predictive value (80.0% v 62.9%), and negative predictive value (89.5% v 80.8%) of SPTs were higher than those of ELISAs. The mean weal size of reaction to reactive dye was weakly correlated with the ELISA optical density of IgE to reactive dye conjugate in patients with occupational asthma from reactive dyes (n=41, r=0.337, p<0.05). In four patients with occupational asthma from reactive dyes and eight control subjects exposed to reactive dye, IgE specific to reactive dye conjugated to HSA was detected with ELISA even though they showed negative skin reactivity. Six patients completely avoided the reactive dye for a mean (SD) 27.8 (10.3) months, IgE specific to reactive dyes decreased in all six patients (p<0.05) during this time.
CONCLUSIONS—Both SPTs and detection of IgE specific to reactive dye in serum samples could be valuable for screening, diagnosis, and monitoring occupational asthma resulting from exposure to reactive dyes. These two tests would complement each other.


Keywords: reactive dye; occupational asthma; skin prick test     

Cerebrotendinous xanthomatosis in three siblings from a Chinese family

Cerebrotendinous xanthomatosis (CTX) is exceptionally rare in the Chinese population. We reported a 31-year-old Chinese male in Hong Kong, who has the characteristic features of cerebrotendinous xanthomatosis including the multiple xanthomas of tendons, mental retardation, bilateral cataracts, cerebellar ataxia and spasticity of the left arm, high concentrations of plasma phytosterols and abnormal MR of brain. On screening the family, two other siblings of 27 and 29 respectively, have tendon xanthomas and high plasma phytosterols. An extensive search of the international medical literature, including the Medline, has revealed only one other case report of cerebrotendinous xanthomatosis in Taiwan. CTX is a potentially treatable disease. It is hoped by alertness, early diagnosis and treatment can be made, and hence prevent further progression of the disease.     

Morphologic evaluation and integrin expression profile of renal tubular cells cultured from percutaneous renal biopsy specimen

Kidney biopsy is an indispensible procedure for making a pathologic diagnosis of renal diseases by fixing and staining the biopsy specimen. However, it is not a routine procedure to culture the cells from a renal biopsy specimen directly, or to utilize the cultured cells for any kind of diagnostic or functional evaluation. In this study, primary culture of the renal tubular epithelial cells was tried from a piece of percutaneous kidney biopsy specimen. Successive passages of the cells were possible until fourth passage. With these cells, morphologic characteristics of the cultured cells and integrin expression profiles were investigated. On light and electron microscopy, these cells were characterized by the cobblestone-like growth, presence of microvilli and tight junction, and the preservation of polarity. Immunohistochemical studies demonstrated the epithelial nature of these cells and particularly their differentiation from renal tubular epithelial cells, of either proximal or distal nephronic segment. The integrin profile confirms the epithelial nature of the cell. We hope that our results facilitate the understanding of pathophysiology of renal tubular cells from the patient directly.     

Water-Soluble and Low Molecular Weight Chitosan-Based Plasmid DNA Delivery

Purpose. Chitosan, a natural cationic polysaccharide, is a candidate non-viral vector for gene delivery because of its high positive charges and low cytotoxicity. In this study, low molecular weight chitosan (LMWC, molecular weight of 22 kDa) was characterized and evaluated as a gene carrier. Methods. Plasmid/LMWC complex was analyzed in 1% agarose gel electrophoresis. To confirm that the LMWC protected plasmids from nuclease, DNase I protection assays were performed. pSV--galactosidase plasmid/LMWC complex was transfected into 293T cells and transfection efficiency was evaluated by -galactosidase assay. Cytotoxicity of LMWC was determined by MTT assay. Results. Unlike high molecular weight chitosan (HMWC), LMWC is highly water soluble, and can form complex with plasmids in physiological buffer. The plasmid DNA was completely retarded at a weight ratio of 1:2 (plasmid:LMWC) in 1% agarose gel. DNase I protection assay showed that plasmids were protected from DNase I over 60 min. The most efficient transfection was obtained at a weight ratio of 1:3 (plasmid:LMWC). The transfection efficiency of LMWC was significantly higher than naked DNA and higher than poly-L-lysine (PLL). MTT assay showed that LMWC was less cytotoxic than PLL. Conclusions. LMWC is non-toxic and has higher transfection efficiency than PLL. Therefore, LMWC will be useful in the development of safe gene carriers.     

Behçet's disease: diagnostic and prognostic aspects of neurological involvement

This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n=18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet's syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet's syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7±2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.