Influence of periosteum on donor healing after harvesting hard palate mucosa

The authors report the influence of periosteum on healing of palatal defect based on more than 10 years of experience of harvesting hard palate mucosa. Between June of 1991 and May of 2001, the authors harvested 80 hard palate mucosae as graft material for skin and mucosa defects. All grafts were harvested from the center of the hard palate. Patients ranged in age from 10 to 82 years old. Of 80 mucosae, 54 were harvested with periosteum, and periosteum was not retained in the defect bed. The other 26 mucosae were harvested without periosteum, which was therefore retained in the defect bed. The healing time increased depending on the defect size in both groups of patients retaining and not retaining periosteum. There was a significant relationship between the defect size and healing time in both groups (Spearman's rank correlation test, p < 0.0001 in both groups). In the two groups, there was no significant relationship between patient age and healing time in the patients with defect smaller than 1.99 cm or larger than 2.00 cm2. There were no significant differences in the rate of patients with pain and bleeding between the groups retaining and not retaining periosteum. In the group not retaining the periosteum, all 54 patients showed a flat or atrophic smooth surface at more than 6 months after epithelization and had no discomfort. However, 17 patients showed flat or atrophic smooth surface in the group retaining the periosteum and the remaining 9 patients showed hypertrophy at more than 6 months after epithelization, with accompanying discomfort. The rate of the patients with hypertrophy in the group of patients retaining periosteum was significantly high as compared with that in the group of patients not retaining periosteum (p = 0.000013, Fisher's exact test). In 26 patients retaining periosteum, the age of the patients with hypertrophic surface was significantly younger than that of the patients with flat or atrophic surface (p = 0.0010, Welch's -test), and the defect size in the patient with hypertrophic surface was significantly smaller than that of the patients with flat or atrophic surface (p = 0.0028, Welch's t-test). In conclusion, our study demonstrated that the existence of periosteum in the palate donor bed does not contribute to reduced healing time or reduced pain. Rather, retaining the periosteum caused hypertrophy of the donor site, leading to discomfort, especially in young patients with a comparatively small defect.     

An extract of the root of Lithospermun erythrorhison accelerates wound healing in diabetic mice

Many people suffer from intractable bedsores, which sometimes develop because of chronic metabolic failure in patients. An extract of the root of Lithospermun erythrorhison (SK) has been reported to have an effect on wound healing. However, the effects of SK have not been studied in chronic wounds, such as bedsores. The healing-impaired diabetic (db/db) mouse is a good model for the investigation of clinical healing therapies. Therefore, we examined whether SK accelerates wound healing in db/db mice. Full-thickness round wounds of 6-mm diameter were created on the backs of mice. After applying SK, we covered the wound with a film dressing to keep it moist. At three weeks, wound closure was complete in SK-treated mice but not in controls. Capillary vessel number and collagen synthesis increased early in wound healing in SK-treated wounds. At this time, vascular endothelial growth factor (VEGF)-positive neutrophils had infiltrated the wound and the appearance of apoptotic fibroblasts and endothelial cells in the granulation tissue was more advanced than in the controls. Where the wound was covered with epithelium, there tended to be less infiltration of VEGF-positive cells and apoptotic cells. These results suggest that the inflammatory phase was shortened, and the proliferative and maturation phases were advanced by SK. It is known that SK also has antibacterial activity. Therefore, we conclude that SK is useful for wound healing in db/db mice, and could potentially help patients with intractable bedsores.     

Xanthogranulomatous cholecystitis: importance of chemical-shift gradient-echo MR imaging

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Comparison of hepatotoxicity and metabolism of butyltin compounds in the liver of mice,rats and guinea pigs

The hepatotoxicity of tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was compared among mice, rats and guinea pigs in vivo. Further, the metabolism of these butyltin compounds in the liver was also investigated in these species. The oral administration of TBTC and DBTC to mice induced obvious liver injury, as demonstrated by both serodiagnosis and histopathological diagnosis. The concentrations of TBTC and DBTC that induced hepatotoxicity in mice at 24 h after oral administration were 180 and 60 micro mol/kg, respectively. In the case of rats, the liver injury induced by TBTC and DBTC was detected at 24 h by the serodiagnosis, but not by histopathological diagnosis. On the other hand, in guinea pigs, TBTC and DBTC administration did not produce any clear liver injury at 24 h, as evaluated by these two diagnostic methods. Thus, the following ranking was obtained with regard to increasing order of sensitivity to liver injury caused by TBTC and DBTC: mice, rats and guinea pigs. The total butyltin contents in the liver of mice were equivalent at 3 h and 24 h after the administration of TBTC or DBTC; however, the contents in the liver of rats and guinea pigs were relatively lower at 3 h and higher at 24 h than those of mice, although there were no differences between rats and guinea pigs in the total liver butyltin content. Concerning the liver metabolism of these butyltin compounds, the main form of butyltin compounds in these animals treated with TBTC was DBTC within 3 h after oral administration, while the main metabolites at 24 h were different in each species, indicating that the liver metabolism of TBTC might vary by animal type. When the animals were treated with DBTC orally, DBTC was hardly metabolized in the livers of these animals even at 24 h, and the liver levels of DBTC were two times greater in mice and guinea pigs than in rats at 3 h and were lower in mice at 24 h than in rats and guinea pigs. The analysis of cellular distributions of DBTC in the liver at 3 h after the administration showed that the levels of DBTC in the nuclear, microsomal and mitochondrial fractions of mice hepatocytes were relatively higher than in those of rats, which were greater than in those of guinea pigs. These results suggest differences in the sensitivity of mice, rats and guinea pigs to hepatotoxicity caused by butyltin compounds and demonstrate that the difference in the sensitivity of these animals to the hepatotoxicity induced by TBTC and DBTC may be partly due to differences in hepatic metabolism of TBTC and in the distribution of DBTC within cell organelles, respectively.     

Effects of insulin-like growth factor I on climbing fibre synapse elimination during cerebellar development

Functional neural circuit formation includes the process by which redundant synaptic connections formed earlier during development are subsequently eliminated. We report that insulin-like growth factor I (IGF-I) is a candidate factor that influences the developmental transition from multiple to mono innervation of cerebellar Purkinje cells (PCs) by climbing fibres (CFs). Continuous local application of exogenous IGF-I to the mouse cerebellum by means of ethylene-vinyl acetate copolymer (Elvax) significantly increased the degree of multiple CF innervation, when the IGF-I containing Elvax was implanted at postnatal day 8 (P8). In contrast, the IGF-I application starting at P12 had no effect on CF innervation. Conversely, continuous local application of antisera against IGF-I and its receptor significantly decreased the degree of multiple CF innervation when the application started at P8. We found that chronic treatment of exogenous IGF-I from P8 significantly enhanced the CF-mediated excitatory postsynaptic currents (CF-EPSCs). This effect was manifest for the smaller CF-EPSCs but not for the largest CF-EPSC of the multiple-innervated PCs. Conversely, chronic application of antisera from P8 caused attenuation of the largest CF-EPSCs. Other parameters for basic synaptic functions and cerebellar morphology were largely normal after the IGF-I or antisera treatment. These results suggest that IGF-I enhances the strength of developing CF synapses and may promote their survival, whereas the shortage of IGF-I impairs the development of CF synapses and, as a result, may facilitate their elimination. Thus, IGF-I is a potentially important factor among various signalling molecules that can influence CF synapse elimination during cerebellar development.     

Synchronous bilateral mucoepidermoid carcinoma of the parotid gland

It is rare for a parotid gland tumour to arise bilaterally, the most common example being Warthin's tumour. Furthermore, it is rare for a parotid gland cancer to occur bilaterally. Here, we describe a case of synchronous bilateral mucoepidermoid carcinoma arising in the parotid gland. A case of bilateral facial nerve dysfunction is presented in which aggressive surgery failed to save the life of a 48-year-old man. This is the first such case reported in the available English literature.     

Adult Leigh syndrome with mitochondrial DNA mutation at 8993

Adult onset Leigh syndrome with a nucleotide (nt) 8993 mutation in mitochondrial (mt) DNA is reported. A 43-year-old woman with a 6-year-history of insulin-resistant diabetes mellitus developed muscular weakness, intractable nausea and vomiting, and anemia. These were followed vertigo, blindness, and deafness with nystagmus. Magnetic resonance imaging (MRI) revealed abnormal high intensities in the bilateral medial regions of the thalamus and periaqueductal gray matters. Autopsy disclosed well-demarcated necrotizing lesions with prominent capillaries in the areas detected by MRI, which were sufficiently diagnostic for Leigh syndrome. MtDNA analysis performed on DNAs extracted from formalin-fixed tissues including liver, heart, brain, muscle, kidney and pancreas showed a T→G mutation at nt 8993. This is the first case of adult Leigh syndrome demonstrating on mtDNA mutations. Received: 24 August 1998 / Revised, accepted: 21 October 1998     

Mxi1 Mutations in Human Neurofibrosarcomas

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor celllines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.     

Familial idiopathic hypoparathyroidism and progressive sensorineural deafness

Three cases from two families with idiopathic hypoparathyroidism and progressive sensorineural deafness are described. Cases 1 and 2 were siblings. Case 3 was one of four siblings from another family. All of them had both idiopathic hypoparathyroidism and progressive sensorineural hearing loss. There was no evidence to suggest involvement of autoimmune mechanism in these cases except for the associated Graves' hyperthyroidism in case 3. Human leukocyte antigen A9 and A11 were positive in both families. The sensorineural hearing loss was progressive even after the treatment for hypoparathyroidism. As the familial idiopathic hypoparathyroidism is a very rare entity, it is unlikely that this disease is associated with familial progressive sensorineural deafness by chance. The combination of these two diseases may compose a new syndrome.