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Background: Although a fundamental treatment for Fukuyama congenital muscular dystrophy (FCMD) is not developed yet, several reports have suggested that steroid therapy could be effective for FCMD; however, no independent intervention studies have been conducted.Objective: This study aimed to evaluate the efficacy of steroid therapy for restoring motor functions in FCMD patients.Subjects: This study involved 3-to-10-year-old FCMD patients who exhibited a decline in motor functions, requested steroid therapy.Methods: The dose regimen started with oral administration of prednisolone at 0.5 mg/kg every other day and was increased to 1.0 mg/kg if the response was insufficient. The motor functions of the patients were evaluated and compared using the Gross Motor Function Measure (GMFM). Statistical analysis was performed using the Wilcoxon signed-rank test (significance level, P ≤ 0.05)Results: The mean age of FCMD patients at the onset of steroid therapy was 8.10 years (SD, 2.14 years). The mean GMFM difference between before and after the steroid therapy was +1.23 (SD, 1.10), with a P value of 0.015 representing a significant improvement in the GMFM.Conclusions: Our results indicate that steroid therapy may contribute to the maintenance and improvement of the motor functions of advanced-stage FCMD patients.Clinical Trial Registration: Registration Number: UMIN000020715, Registration Date: 01/02/2016.

PURPOSE/OBJECTIVE(S) Stereotactic body radiotherapy (SBRT) is an emerging non-invasive treatment in the management of cardiac arrhythmias. The purpose of this research is to evaluate the MR imaging in the detection of radioablation lesion at the cavotricuspid isthmus (CTI) in mini pigs. MATERIALS/METHODS Four mini pigs underwent magnetic resonance (MR) evaluation of heart function and invasive electrophysiology assessment using electroanatomical mapping (EAM) before and 3 months after SBRT with single-fraction doses of 25Gy at the CTI. SBRT simulation, planning, and treatments were performed with the use of standard techniques. MR examination, including diffusion-weighted MRI, dynamic Gd-enhanced MRI, MR spectroscopy, and T2-weighted MRI were performed before and 3 months after SBRT, followed by histopathologic examination. One radiation oncologist and one radiologist evaluated the detectability and image quality for the irradiated site. MRI findings of the CTI radioablation lesion was compared to electrophysiology and histopathology findings. RESULTS A total dose of 25 Gy was delivered to the CTI (median volume of 25 cc) in a single procedure according to the radiation therapy oncology group. The mean radiation dose to the heart was 7 Gy. The maximal doses (< 0.05 cc) to the left and right coronary arteries were 14 Gy and 13 Gy, respectively. EAM visualized the irradiated site and confirmed clockwise conduction block across the CTI. Gd-enhanced T1-weighted imaging could only detect the irradiated site. There were no statistical differences in the image quality of the all MR images. CONCLUSION These data demonstrated the feasibility of SBRT for creating conduction block across the CTI in mini pigs. Gd-enhanced T1-weighted imaging was essential in assessing the radioablation lesion.

Caveolinopathies, caused by CAV3 mutations, can include several phenotypes such as rippling muscle disease, limb-girdle muscular dystrophy type 1C, distal myopathy, familial hypertrophic cardiomyopathy, and idiopathic hyperCKemia. Here we present characteristic skeletal muscle imaging findings in four patients with genetically defined childhood-onset RMD caused by CAV3 mutations and in one patient with congenital generalized lipodystrophy type 4 with muscular dystrophy due to polymerase I and transcript release factor (PTRF) mutations, which may have caused secondary deficiency of caveolin-3. Muscle MRI revealed that the rectus femoris and semitendinosus muscles were most commonly affected in the rippling muscle disease patients. Peripheral changes in the rectus femoris were specific and observed even in one of the younger patients in this study. Furthermore, muscle involvement extended to the semitendinosus muscles, biceps femoris, and gracilis with disease progression or increase in its severity. Similar patterns of involvement were observed on reviewing skeletal muscle images of various previously reported phenotypes of caveolinopathy; interestingly, patients with secondary deficiency of caveolin due to PTRF mutations revealed the same pattern. Thus, primary caveolinopathies and secondary deficiency of caveolin demonstrated specific findings on skeletal muscle imaging, regardless of the broad phenotypic spectrum of these two conditions.

Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

We report on two Japanese siblings with Wolfram syndrome (WS) who were identified as carrying a novel mutation in Wolfram syndrome 1 (WFS1). The homozygous mutation, Y652X in exon 8, has not been reported in WS or low-frequency sensorineural hearing loss previously. The substitution is located at the beginning of the C-terminus of the protein, which is typically localized to the lumen of the endoplasmic reticulum (ER). This mutation predicts a truncated protein of 651 aa, with deletion of the entire C-terminal peptide, and was suggested to cause a severe phenotype. They developed a typical presentation, including symptoms such as deafness, diabetes insipidus, and visual disturbances at younger ages compared to those reported in the review. Moreover, they were also diagnosed with attention deficit hyperactivity disorder (ADHD), a neuropsychiatric disorder that manifests in early childhood as a deviation from normal development at the ages of 3 and 5 years. WS is known to be associated with neurological and psychiatric disorders, such as severe depression. However, co-occurrence of ADHD and WS has not been found in the literature; these cases were also interesting in this aspect.

Two patients with cardiac metastasis from head and neck cancer are reported. Cardiac metastasis located in the left atrium was detected on a follow-up computed tomography (CT) scan 15 months after partial glossectomy for a tongue carcinoma in a 60-year-old man. The diagnosis was confirmed as cardiac metastasis of squamous cell carcinoma (SCC) by surgical excision of the cardiac lesion. The patient died 3 weeks after surgery. In a 69-year-old man with a partial maxillectomy for primary soft palate cancer, a follow-up CT scan 5 months after surgery revealed a mass in the right atrium and ventricle, and multiple lung metastases. He died of heart failure 3 weeks after the diagnosis of cardiac metastasis. Information on these cases should add to knowledge about rarely encountered cardiac metastasis.

Carotid duplex sonography is a useful method for evaluation of dural arteriovenous fistulas. The resistance index of the external carotid artery has been reported to correlate with the efficacy of treatment and recurrence or aggravation of dural arteriovenous fistulas. Herein, we describe a case of dural arteriovenous fistulas mainly supplied by the occipital artery and show that the resistance index of the occipital artery was more sensitive than that of the external carotid artery. To the best of our knowledge, this is the first report to describe the feasibility of occipital artery detection by carotid duplex sonography and clinical application of the resistance index of the occipital artery for dural arteriovenous fistulas.

Summary This study examined the immediate effects of wrapped warm footbaths (WW Footbath) on the autonomic, neuroimmunological and psychological activities in healthy middle-aged volunteers. Thirteen subjects were divided into a footbath group ( n =7) and a control group ( n =6). Immediate changes in autonomic activities were recorded with wavelet analysis of heart rate variability. Salivary secretory immunoglobulin A (sIgA) and serum cortisol levels were used as neuroimmunological parameters. Psychological conditions were measured using a Visual Analog Scale. Parasympathetic activity tended to increase and sympathetic activity decrease after footbaths. Results Changes in the relaxation indices, that is, sIgA and serum cortisol levels showed that both lying down and footbath resulted in a relaxed state. Conclusion: WW Footbaths can be an effective method of relaxation, since it induces both a significant increase in parasympathetic activity and significant decrease in sympathetic activity.

An unusual primary adenomatoid tumour arising in the normal liver is described. Hepatectomy was performed, and the patient is alive and free of disease 1 year postsurgery. Grossly, the tumour showed a haemorrhagic cut surface with numerous microcystic structures. Histological examination revealed cystic or angiomatoid spaces of various sizes lined by cuboidal, low-columnar, or flattened epithelioid cells with vacuolated cytoplasm and round to oval nuclei. The epithelioid cells were entirely supported by proliferated capillaries and arteries together with collagenous stroma. Immunohistochemical studies showed that the epithelioid cells were strongly positive for a broad spectrum of cytokeratins (AE1/AE3, CAM5.2, epithelial membrane antigen and cytokeratin 7) and mesothelial markers (calretinin, Wilms' tumour 1 and D2-40). These cells were negative for Hep par-1, carcinoembryonic antigen, neural cell adhesion molecule, CD34, CD31 and HMB45. Atypically, abundant capillaries were observed; however, the cystic proliferation of epithelioid cells with vacuoles and immunohistochemical profile of the epithelioid element were consistent with hepatic adenomatoid tumour.

In this paper, ion-implantation technique was applied to improve corrosion resistance of a newly developed La-based bulk metallic glass with poor corrosion resistance. It is found that the alloys after ion implantation with doses ranging 6 × 1016–1 × 1017 Nb/cm2 have a remarkable enhancement of corrosion resistance in chloride containing environments and acid solution with respect to the alloy without the surface treatment while the implanted alloys still have high glass forming ability. The improvement of corrosion resistance for the implanted alloys is attributed to the high passivating ability of the Nb-containing surface layer. These results obtained here clearly demonstrate that the ion-implantation technique could be a useful method to improve the corrosion resistance of bulk metallic glasses without losing glass forming ability of alloys.

The microsurgical anatomy of the lateral ventricles was examined in cadaveric cerebral hemispheres. The neural, arterial and venous structures in the wall of the lateral ventricles, the relationships of the lateral ventricles to the velum interpositum and third ventricle were examined. The relationships of the choroidal fissure and basal cisterns were also examined. The operative approaches to the lateral ventricles are reviewed and several clinical cases are presented.

Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.

We developed an anti-immune complex (IC) ELISA applicable to direct determination of trace amounts of microcystins (MCs) in tap water. Comparison of two assay formats revealed that the use of anti-immune complex monoclonal antibody (MAB) in the coating step to trap anti-MC MAB–MC complexes improved the sensitivity as well as precision. The detection limit and quantitative range of the IC ELISA was 2 pg ml−1 and 2–100 pg ml−1 of microcystinLR (MCLR), respectively, indicating the most sensitive of all the methods for detecting MCs reported to date. Additionally, the IC ELISA maintained good reliability through its quantitative range, as evidenced by low coefficients of variation (5.0–10.8 and 4.9–10.2% for intra- and interassay, respectively). The IC ELISA showed good cross-reactivity to microcystin-RR and microcystin-YR, suggesting major MCs found in the environment can be detected by this method. Recovery tests in which quantitative range of MCLR were added to tap water resulted in a mean recovery of 99%,...

To investigate whether common variants in the human genetic background are associated with pathogenesis of ischemic heart diseases, we systematically surveyed 41 possible candidate genes for single-nucleotide polymorphisms (SNPs) by directly sequencing 96 independent alleles at each locus, derived from 48 unrelated Japanese patients with myocardial infarction, including 25.8 kb 5' flanking regions, 56.8 kb exonic and 35.4 kb intronic sequences, and 1.8 kb 3' flanking regions. In this genomic DNA of nearly 120 kb, we identified 187 SNPs: 55 in 5' flanking regions, seven in 5' untranslated regions (UTRs), 52 in coding elements, 64 in introns, eight in 3' UTRs, and one in a 3' flanking region. Among the 52 coding SNPs, 26 were non-synonymous changes. Allelic frequencies of some of the polymorphisms were significantly different from those reported in European populations. For example, the Q506R substitution in the coagulation factor V gene, the so-called "Leiden mutation", has a reported frequency of 2.3% in Europeans, but we detected the Leiden mutation in none of the Japanese genomes that we investigated. The allelic frequencies of the –33A>G SNP in the thrombomodulin gene were also very different; this allele occurred at a 12% frequency in the Japanese patients that we examined, although it had been detected in none of 82 Caucasians reported previously. These data support the hypothesis that some SNPs are specific to particular ethnic groups.

To investigate the nature of extraocular pseudoexfoliative (PSX) material, and to validate the hypothesis that the PSX syndrome is a systemic disorder, we studied the immunoreactivity of intraocular and extraocular PSX material from patients with the PSX syndrome using antibodies against proteins of extracellular matrices. Surgical specimens of four different tissues were obtained from human eyes with the PSX syndrome: nine trabecular tissues, three cataractous lenses, six bulbar conjunctivas, and seven lid skins. These tissues were processed for electron microscopic immunohistochemistry, and stained with antibodies against vitronectin, fibronectin, laminin, and elastin, by an indirect immunogold procedure. Density of the gold particles located on the PSX material was estimated by video image analysis. Statistical analysis of the data revealed that the PSX material from trabecular tissues, lenses, bulbar conjunctivas, and lid skins had almost identical immunoreactivity to the antibodies studied. PSX materials of trabecular tissues, lenses, bulbar conjunctivas, and lid skins were found to have not only a similar ultrastructure, but also almost identical immunohistochemical characteristics. These results support the hypothesis that the PSX syndrome is a systemic disorder.

A virtual reality system using a head mounted display (HMD) was constructed for the purpose of finding out how human beings perceive the three-dimensional world. Four ophthalmologically normal subjects and 4 strabismic patients (2 with exotropia, 2 with esotropia) were examined. They wore the HMD and viewed some familiar objects (e.g. human face) and an unfamiliar object (e.g. tangled ropes) under normal parallax, reversed parallax, and monocular conditions. They also attempted the ring and hook test under each condition. They recognized the normal familiar objects under each condition, but some normal subjects were confused when they perceived unfamiliar objects. The normal subjects barely passed the ring and book test under the reversed parallax condition. The results of the strabismic subjects showed change under each condition. Stereoptic ability in normal and strabismic patients were considered based on the above. Also considered were some stereoptic keys, binocular parallax, monocular stereoptic keys such as shadows, shades, texture, etc., the near reflex and the fact that the objects were familiar. It was found that the strabismic patients used monocular stereoptic keys more than normal people to supplement their lack of binocular parallax perception.

We examined surgically induced astigmatism following 6.5-mm incisions between 9 and 12 o'clock (BENT incision) in 50 cases with cataracts who underwent phacoemulsification-aspiration and 6-mm intraocular lens implantation. The surgically induced astigmatism (n = 50) shifted to against-the-rule astigmatism (ATR; -0.03 +/- 0.95 dpt) 1 day after the operation and then tended to shift to with-the-rule astigmatism (WTR). The results of a group with preexisting ATR (> 2 dpt; n = 4) were similar to the results of the aforementioned group, whereas the results of a group (n = 7) with preexisting WTR (> 2 dpt) were different. Astigmatism in this group shifted to ATR of about 1.0 dpt. This study suggests that the BENT incision procedure can reduce both preexisting WTR > 2.0 dpt and preexisting ATR > 2 dpt.

Aim The aim of this study was to compare the growth of Japanese infants that were exclusively breastfed to those of national references and World Health Organization (WHO) standards. Methods Mothers, who delivered a normal term baby and had been exclusively breastfeeding for at least 4 months, were enrolled. The lengths, body weights and head circumferences of 647 children, aged 0–24 months, were obtained and compared to national references and WHO standards. Results Comparisons of the national references for both length and body weight indicated that breastfed infants were significantly shorter and lighter almost throughout the first 24 months. Conversely, head circumferences of breastfed infants were significantly larger at 1 and 6 months of age in boys and 6 months in girls. Compared to WHO standards, similar trends to the comparisons with national references were found. Conclusion There were significant differences identified between the growth of breastfed infants and existing national references and WHO standards.

We report the effects of thrombospondin (TSP) on the proliferation of four different human hepatocellular carcinoma (HCC) cell lines (HuH-7, KIM-I, KYN-2, and KYN-3) and report the proliferative activity of HuH-7 cell using microspectrophotometry. The addition of anti-TSP neutralizing antibody (150, 1500, or 15000 ng/ml) to cultured medium showed marked suppression of cell proliferation in all cell lines. On the other hand, the addition of exogenous TSP (20 or 40 mu g/ml) to culture medium stimulated cell proliferation, in KYN-2 and KYN-3 but not in HuH-7 or KTM-1. Furthermore, in DNA measurements on HuH-7 cells, the effect of the anti-TSP neutralizing antibody induced growth arrest in the G(0)/G(1) phase of the cell cycle and decreased DNA synthesis. In conclusion, TSP promoted the proliferation of HCC cells, and based on our results it is predicted that TSP might act through an autocrine or paracrine growth-supportive mechanism in the extracellular matrix.

X-linked myotubular myopathy (XLMTM), one of the most severe forms of centronuclear myopathy Cis caused by mutations in the MTM1 gene. XLMTM usually has a neonatal onset requiring respiratory support due to severe respiratory muscle weakness and patients remain bed-ridden. The few past reports on skeletal muscle imaging of the lower limbs in XLMTM patients showed involvement of the soleus muscles and of the posterior thigh. We present the magnetic resonance imaging (MRI) findings of both upper and lower limbs in an XLMTM patient, who survived with Non-invasive Positive Pressure Ventilation (NPPV) support and ultimately became ambulatory. The patient was a 12-year old boy. His older brother, who also had XLMTM, had died during infancy. The patient presented with reduction of fetal movements, and had needed artificial respirator support at birth. He was genetically diagnosed as having XLMTM. Although he suffered repeated exacerbations of respiratory failure due to infection, the frequency of mechanical ventilation decreased after the initiation of NPPV at the age of 21 months. He obtained an independent gait at the age of 7 years, and he also gained the ability to walk up the stairs while holding onto a railing. T1-weighted muscle MRI tended to show high intensity areas in the flexor group of both brachial muscles and muscles in the forearms. Whole muscles in the thighs were mildly affected, but the soleus muscles were preserved. We have presented a rare XLMTM case achieving satisfactory progress. Muscle imaging showed differences from past reports in terms of the affected muscles. The degree of muscle atrophy was milder, most notably, than previously thought. This is consistent with our patient’s good clinical course. We speculate that skeletal muscle MRI shows specific muscle involvements also in the upper limbs. We advocate accumulating muscle imaging data not only for the lower but also for the upper limbs, to shed further light on the pathophysiology of XLMTM.

We studied the frequency and grade of atherosclerotic changes in the thoracic aorta and their significance as embologenic lesions in patients with stroke. Using transesophageal echocardiography, we evaluated complicated lesions in the thoracic aortas of 62 patients who met our clinical criteria for embolic stroke. A complicated lesion was defined as a raised lesion with an irregular surface or acoustic shadow based on a comparative study of echocardiographic and histopathologic findings. The results were compared with plain radiographic findings and in some cases with computed tomographic or aortographic findings. Twenty-six patients (42%) showed complicated aortic arch lesions on echocardiogram. Transesophageal echocardiography brought us more abundant information than other techniques. Aortic knob calcification by plain radiography correlated well with the presence of echocardiographically complicated lesions, suggesting its utility for rough screening of atherosclerotic changes. Fifty-two patients had other potential embolic sources in the heart or cervical arteries. Among the remaining 10 patients without extra-aortic embolic sources, three showed complicated lesions and were diagnosed as having aortogenic embolic stroke. Aortic atherosclerosis should be recognized as an embolic source of stroke and the advantage of transesophageal echocardiography recognized in its evaluation.

To determine adequate and effective balloon diameters of the Inoue balloon catheter, we reviewed clinical results and characteristics of the Inoue balloon catheter, especially the relationship between the intra-balloon pressure and the balloon diameter, experimentally and clinically, in 46 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Mitral valve area increased from 1.1 +/- 0.3 to 2.1 +/- 0.3 cm2 in all patients after PTMC. Based on balloon diameter settings, mitral valve area increased from 1.3 +/- 0.4 to 2.3 +/- 0.5 cm2 in patients treated with a balloon setting greater than 26 mm in diameter, from 1.1 +/- 0.3 to 2.0 +/- 0.5 cm2 in patients with a balloon setting at 26 mm in diameter, and from 1.1 +/- 0.4 to 1.7 +/- 0.4 cm2 in those treated with a balloon setting less than 26 mm in diameter, with an increase in mitral valve area of 1.0 +/- 0.6, 0.9 +/- 0.4, and 0.7 +/- 0.2 cm2, respectively. There was a significant difference between the increase in mitral valve area at a setting of 26 mm in diameter and that observed at a setting less than 26 mm in diameter. We next investigated differences between balloon diameter settings and actual balloon diameters measured from cineangiograms at maximum balloon inflation. The ratio of actual balloon diameter to a setting diameter of less than 26 mm was smaller than that of 26 mm. To evaluate the reason for the difference, we investigated the relationship between intra-balloon pressure and balloon diameter. In the prototype Inoue balloon catheter, intra-balloon pressure increases from 1.0 kg/cm2 at 20 mm in diameter to 2.2 kg/cm2 at 30 mm in diameter at atmospheric pressure. In conclusion, the increase in mitral valve area was inadequate when the balloon was less than 26 mm in diameter because of inadequate intra-balloon pressure. We, therefore, recommend a balloon size set above 26 mm to obtain adequate intra-balloon pressure when using the Inoue balloon catheter.

Background and aim Several uncontrolled studies have reported on the efficacy of adsorptive depletion of peripheral blood granulocytes and monocytes/macrophages (GM) in patients with moderate or severe ulcerative colitis. This study was to compare the efficacy and safety of intensive GMA with intensive intravenous prednisolone in patients with severe ulcerative colitis. Methods Seventy patients with clinical activity index 10–23 were randomly assigned to intensive GMA with the Adacolumn, at 2 sessions/week in the first 3 weeks and then 1 session/week for up to 11 sessions (n = 35) or intravenous prednisolone, 40–60 mg/day for 5–10 days (n = 35). No patient received immunomodulators within 8 weeks prior to entry. Clinical response based on intention to treat was assessed at weeks 2, 6 and 12. Results Four patients in the prednisolone group and two patients in the GMA group discontinued in week 1. At weeks 2, 6 and 12, the remission (clinical activity index ≤ 4) rates (%) in the GMA group were 17.1, 54.4, 74.3, respectively. The corresponding values in the prednisolone group were 25.7, 51.4 and 48.6. Further, at week 12, 27 patients (77%) in the GMA group and 5 patients (14%) in the prednisolone group were steroid free (P = 0.0076). In the GMA group, flushing and light-headedness were observed in 5 patients versus typical steroid side effects in 29 patients of the prednisolone group. Conclusions In this clinical response to GMA was comparable or better than prednisolone. Further, the response to GMA was slower than to intravenous prednisolone, but was more sustainable than the latter.

Two-piece hard shell capsules made from hypromellose (or hydroxypropyl methylcellulose, HPMC) have been proposed as an alternative to conventional gelatin capsules for oral drug delivery; however, little is known about their in vivo behaviour. The aim of this study was to compare the disintegration of HPMC and gelatin capsules in fasted human subjects using the technique of gamma scintigraphy. HPMC capsules containing carrageenan as a gelling agent (QUALI-V(R), Qualicaps) and gelatin capsules (Qualicaps) of size 0 were filled with a lactose-based mixture. The capsules were separately radiolabelled with indium-111 and technetium-99m. Both capsules were administered simultaneously with 180ml water to eight healthy male subjects following an overnight fast. Each volunteer was positioned in front of the gamma camera and sequential 60s images were acquired in a continuous manner for 30min. No differences in the oesophageal transit of the two types of capsules were noted, with the capsules arriving in the stomach in a matter of seconds. All the capsules disintegrated in the stomach. The mean (+/-S.D.) disintegration time for the HPMC capsules was 9+/-2min (range 6-11min). The corresponding mean time for the gelatin capsules was 7+/-4min (range 3-13min). These disintegration times were not significantly different (P=0.108, paired t-test). In conclusion, HPMC and gelatin capsules show rapid and comparable in vivo disintegration times in the fasted state. HPMC capsules containing carrageenan as a gelling agent therefore offer a practical alternative to gelatin capsules as an oral drug delivery carrier.

A new eye microsurgical system is proposed. The final goal of our research project has been not only to improve surgical instruments, but also to establish a total surgical system applicable to today's most difficult microsurgery, within the eye. The new prototype micro-forceps, which have a joint that enlarges the surgical area and a built-in thin optical fibrescope to increase the dexterity of retinal microsurgery, was designed as the first step in a long-term research plan. The micro-active forceps is equipped with a thin optical fibre inside the stem, giving a lateral view of the retina and a drastic improvement in fine operations. Moreover, this new tool, with an active joint and an end-effector, could find application in other microsurgical fields, such as in the brain, ear, nose and throat.

The localization of sialic acid in the trabecular meshworks of the normal human primary open-angle (POAG), congenital and juvenile glaucomatous eyes was investigated using both an electron microscope and lectins specifically binding with sialic acid. Sialic acid was always localized in fine fibrils lying underneath the canal wall and around collagen fibrils of the whole trabecular tissue. In both congenital and juvenile glaucoma, sialic acid was detected not only in the fine fibrils but also in the basement membrane-like materials in compact tissue present 3 μm underneath the canal wall. Sialated glycoprotein appears to play an important role in the pathogenesis of both diseases.

The final goal of the authors' research is establishing a new method applicable to today's most difficult microsurgery on the retina. As a first step, a new type of micro forceps is designed and prototyped. It has two typical features conventional forceps don't have: (1) an active joint which enlarges the operable area on the retina; and (2) a thin optical fiberscope built into the stem enables the surgeon to obtain a lateral view of the diseased part along with the top view-a conventional eye surgeon could only get the top view through the cornea via a binocular microscope. It is very useful visual information to see the distance between the tool's tip and the retina. Thus a drastic improvement of fine operations can be achieved. Moreover, the effectiveness of the micro active forceps was confirmed by a maneuvrability test using pig's eyeballs.

Fukuyama congenital muscular dystrophy (FCMD) is the second most common type of muscular dystrophy in Japan. It is an autosomal recessive disorder caused by mutation in fukutin, characterised by the involvement of the central nervous system, resulting in mental retardation and seizures. We previously reported seizure frequency in FCMD as 62%, and some patients developed intractable seizures. Levetiracetam (LEV) has been administrated to patients with intractable epilepsy as a second line of treatment in Japan. In addition, LEV has been increasingly used for FCMD. Here we investigated the effectiveness of LEV for seizures in FCMD. Patients and methods: Genetically diagnosed FCMD patients, who were administrated LEV were analysed. We defined “extremely effective” when seizures disappeared and “effective” when the seizure frequency decreased by more than 50% after LEV administration. Results: Eight patients received LEV as add-on therapy. The median age was 16 years 5 months. Three patients carried a homozygous mutation and 5 carried a compound heterozygous founder mutation. The seizure types were complex partial or generalized and 3 patients manifested febrile seizures. Three were “extremely effective”, 2 were “effective”, 2 were “non-effective” and 1 was equivocal. Of the 4 “extremely effective” or “effective” patients, 3 required a dose of 20–30 μg/kg and 1 required more than 50 μg/kg of LEV. Three “non-effective” patients did not show any reaction even at a maximum dose. None of the patients manifested any side effect. LEV can be used for partial or generalized seizures and apparent side effect cannot be observed. Furthermore, some patients can react even at a low dose of LEV. LEV can be used for seizures complicated with FCMD because it is effective for both partial and generalized seizures and it does not affect respiratory dysfunction, which is a side effect that is often life-threatening for FCMD patients.

Fukuyama congenital muscular dystrophy (FCMD), among the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy and brain malformations. It is essentially limited to Japan, and three-quarters of Japanese patients have a similar haplotype due to the ancestral founder mutation, a 3-kb retrotransposal insertion in the fukutin gene. Patient phenotypes can be classified as mild, typical, and severe depending on peak motor function. The typical form patients can sit without support or slide on the buttocks and account for 75% of FCMD cases. The patients who can crawl or walk are classified as having mild form and those lacking head control as having severe form. The rate of heterozygosity for the ancestral founder mutation was reported to be significantly higher in severe cases. Since the natural history of FCMD was reported long ago, we aimed to reevaluate the natural history of our FCMD patients. We retrospectively studied the medical records in 73 genetically diagnosed FCMD patients followed at our University from 1995. Forty-four patients were homozygous for the ancestral founder mutation and 24 had a compound heterozygous mutation. In the homozygous group, 28 patients were classified as typical form and 8 as mild form. In the heterozygous group, 13 patients had typical form and 8 had severe form. Head control and sitting without support were achieved, on average, at 7.6 months (m) and 14.6 m of age, respectively, in the homozygous group, but at 16.5 m and 39.1 m in the heterozygous group. Head control and sitting on average for each phenotype were: (i) 4.5 m/9 m in the walking, (ii)7.4 m/17.7 m in the sliding on the buttocks (iii) 10.5 m/21.3 m in sitting without support, and (iv) 21.7 m/- in the severe groups only with head control. Motor function deterioration started at 7.6 years, on average. Detailed assessment of motor development patterns for each FCMD phenotype may facilitate conducting clinical trials.

Fukuyama congenital muscular dystrophy (FCMD), characterized by intellectual deficits and epilepsy with cortical migration defects, is the most common congenital muscular dystrophy in Japan. Most patients die of congestive heart failure or respiratory dysfunction, as in Duchenne muscular dystrophy (DMD), in the second decade of life. Recent studies have found that renal dysfunction is a common complication of advanced DMD and is the third leading cause of death in these patients. Circulatory instability caused by cardiac dysfunction is thought to result in renal dysfunction, especially prerenal failure. We retrospectively evaluated renal function in 37 genetically diagnosed FCMD patients (1.3–32.9 years, mean age 13.7 ± 6.9 years) using Cystatin C. We examined possible relationships of Cystatin with the levels of blood natriuretic peptide and creatinine, as well as the cardiac echo results. Twenty-four patients were treated for cardiac dysfunction, but elevated Cystatin C was detected in only two. These two patients also showed proteinuria, glycosuria, hematuria and extremely high levels of β2-microglobulin on urine tests and were thus diagnosed as having kidney tubule cell damage. Since both patients were treated for intractable epilepsy with many types of antiepileptic drugs, including valproic acid (VPA), and had low serum carnitine levels, kidney tubule cell damage was thought to be an adverse effect of VPA. One patient improved in response to a reduced VPA dose, but the other developed Fanconi syndrome. Unlike DMD patients, none of our FCMD patients progressed to prerenal failure. Though FCMD patients also have cardiac dysfunction, careful fluid management is instituted early because dysphagia emerges in the early stage. In DMD patients, inadequate fluid management may also cause circulatory instability, which can progress to prerenal failure. On the other hand, kidney tubule cell damage should be noted in FCMD patients especially with VPA treatment for epilepsy.

s of the 3rd International Symposium on Pediatric Inflammatory Bowel Disease S433 therapy after bowel resection. Four patients completed 12 months follow-up after surgery on clinical remission. Two of these patients have undergone a control colonoscopy, showing Rutgeerts score i0 and i1. The other 3 patients remain in clinical remission three months after resection. Conclusions: Combined treatment with anti-TNF and AZA has shown to be effective as prophylactic therapy in our patients with CD after bowel resection. P-106 The clinical relevance of tacrolimus for ulcerative colitis in children: a national survey of the treatments for pediatric inflammatory bowel disease in Japan T. Yanagi1 *, K. Ushijima1, T. Shimizu2, T. Tomomasa3, H. Tajiri4, R. Kunisaki5, T. Ishige3, H. Yamada6, K. Arai7, Y. Ohtsuka2, A. Yoden8, T. Aomatsu8, S. Nagata9, K. Uchida10, T. Kazuo11. 1Kurume University School of Medicine, Fukuoka, Japan, 2Juntendo University School of Medicine, Tokyo, Japan, 3Gunma University Graduate School of Medicine, Gunma, Japan, 4Osaka General Medical Center, Osaka, Japan, 5Yokohama City University Medical Center, Kanagawa, Japan, 6Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan, 7National Center for Child Health and Development, Tokyo, Japan, 8Osaka Medical College, Osaka, Japan, 9Tokyo Women’s Medical University Hospital, Tokyo, Japan, 10Mie University Hospital, Mie, Japan, 11Saitama University, Saitama, Japan Aim: To evaluate the effectiveness and safety of FK506 for pediatric UC in Japan. Methods: Fifty-four UC patients aged