Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.     

Relationship of Diet to Small and Large Adenomas of the Sigmoid Colon

The relation of dietary factors to the risk of adenomas of the sigmoid colon was examined in men receiving a retirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and 1990. A total of 187 adenoma cases and 1557 controls with normal colonoscopy were identified in the series. Cases were further classified into small-adenoma (<5 mm, n=78) and large-adenoma (≥5 mm, n=67) groups. The consumptions of selected foods and beverages were ascertained before colonoscopy by means of a self-administered questionnaire. After adjustment for smoking, alcohol use, rank and body mass index, low rice consumption and high meat intake were independently associated with an increased risk of large adenomas. The risk of small adenomas was not related to either rice consumption or meat intake. Adjusted odds ratios of large adenomas for the low, intermediate and high consumption levels of rice were estimated to be 1.0 (referent), 0.83 and 0.43, respectively (trend P = 0.08), and the corresponding figures for meat consumption were 1.0 (referent), 1.58 and 2.38, respectively (trend P =0.02). The findings suggest that low rice consumption and high meat intake may promote the growth of colon adenomas, thereby increasing the risk of colon cancer.     

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.This work was supported by the Grant of Tokuteishitsukan from the Japanese Ministry of Welfare and Health.     

A case of middle-aged onset sialidosis type I]

We reported a patient with middle-aged onset sialidosis type I. A 52-year-old Japanese man was referred to our hospital because of dysarthria, involuntary movement of his extremities and gait disturbance since the age of 46 years. On admission, neurological examination revealed scanning speech, action myoclonus, cerebellar ataxia and cherry-red spots. Vacuolated lymphocytes were found in peripheral blood. Brain 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) showed decreased glucose metabolism in the cerebellum. Enzymological analysis using his skin fibroblasts revealed primary deficiency of sialidase activity. Sialidase gene analysis identified compound heterozygotes for base substitusions of 239T-to-C and 649G-to-A, which resulted in amino acid alterations of P80L and V217M, respectively. These mutations have been reported in Japanese sialidosis type II (P80L) and I (V217M). Further studies are required to reveal effects of gene mutations on residual enzyme activities and phenotypes.     

Seborrhoeic Dermatitis: Treatment with Anti-Mycotic Agents

In order to elucidate the effectiveness of anti-mycotics in treating seborrhoeic dermatitis, an attempt was made to isolate Malassezia from seborrhoeic lesions of patients of seborrhoeic dermatitis. The results revealed that, in male patients, 46/49 cases were positive for Malassezia furfur on the face and 30/48 cases were positive for M. furfur on the scalp. In female patients, 7/13 cases were positive for M. furfur on the face, and 6/17 cases were positive for M. furfur on the scalp. Anti-mycotic agents were excellent in 50% and good in 31% of the spore-positive cases, yielding an overall efficacy rate of 81%. In contrast, the treatment of the face with vehicle alone showed only one excellent result out of 8 cases. Although clinical improvement was rapid on the side treated with a topical corticosteroid in the half-side-test, numerous fungal elements remained. While the improvement with anti-mycotic agents was slower than that with the corticosteroid, clinical improvement became evident by the third week of administration and fungal elements disappeared.     

Amiloride inhibition of responses of rat single chorda tympani fibers to chemical and electrical tongue stimulations

Amiloride inhibition of single fiber responses of the rat chorda tympani to ionic chemical and electrical tongue stimulations was studied. Amiloride reduced responses to both chemical and electrical stimulations with NaCl or LiCl in most of the single fibers. However, the magnitude of reduction of the response by amiloride varied among the fibers and was greater for chemical than electrical stimulation with NaCl in each fiber. Thirty-two single fibers were divided into two groups, such as 18 high (HAS) and 14 low amiloride-sensitive (LAS) fibers. Percent responses (control, 100%) of the former group to chemical stimulus with NaCl after amiloride ranged from 1.1 to 42.5%, while those of the latter from 72.8 to 108.0%. In HAS fibers, amiloride also reduced responses to KCl and CaCl2, but to a smaller degree than those to NaCl and LiCl. Fifteen out of 18 HAS fibers more strongly responded to a chemical stimulus with 0.1 M NaCl than 0.01 M HCl, while the opposite was true for 13 out of 14 LAS fibers, although the threshold concentration for NaCl was rather lower in LAS fibers than in HAS fibers. These results suggest that there exist at least two different receptor mechanisms for NaCl or LiCl which are amiloride-sensitive and -insensitive, and the observed differences in relative specificities to ionic taste stimuli and sensitivities to amiloride among rat chorda tympani fibers are possibly due to a disproportional distribution of these two receptors.     

Clinical usefulness of the WHO histological classification of thymoma.

PURPOSE: Rosai et al. published the World Health Organization (WHO) classification of thymic epithelial tumors in 1999, and its clinical usefulness seems to be established. It is our purpose to find the clinically relevant diagnostic points in the WHO Histological Classification of Thymoma. METHODS: Thymomas surgically removed from 100 consecutive patients at Juntendo University Hospital between October 1983 and February 2002 were classified according to the WHO histological classification. We assessed overall survival and recurrence-free rate calculated for each tumor type in the WHO classification compared with those of tumors classified by the Masaoka system. RESULTS: The thymic epithelial tumors in this series comprised 10 type A, 15 type AB, 18 type B1, 21 type B2, 33 type B3, and 3 type C tumors according to the WHO classification. Based on the Masaoka system, the disease was stage I in 53 patients, stage II in 30, stage III in 15, and stage IV in 2. The 15-year recurrence-free rate was 100% for type A, AB and B1, while the rates for types B2 and B3 were 66.7% and 54.5%, respectively. The 10-year recurrence-free rate was 66.7% for type C. The 15-year recurrence-free rate of the 64 patients with type A, AB, B1, and B2 thymomas was significantly higher from that of the 33 patients with type B3 thymoma (p=0.0026). CONCLUSION: When using the WHO classification, it is critical to distinguish type B3 thymoma from other tumor types.     

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.