Immunohistochemical demonstration of proteoglycans in the skin of patients with systemic sclerosis

Skin proteoglycan was demonstrated by an immunofluorescent technique using an antibody against bovine cartilage proteoglycan, after the cross-reactivity of human proteoglycan with the antiserum had been confirmed. Normal skin exhibited specific fluorescence mainly in the blood vessels as well as in the subepidermal area. The clinically uninvolved skin of systemic sclerosis (SS) revealed no features different from those of normal skin. However, the vascular proteoglycan deposition of early systemic sclerosis was later replaced by deposition between the collagen fibres, which appeared to progress centrifugally in parallel to the increase in the skin sclerosis, suggesting a vascular initiation of the skin lesion. Sclerotic skin was characterized by random deposition between the collagen fibres. Immunoelectron microscopic studies suggested that the random proteoglycan deposition reflected uncontrolled local accumulation of proteoglycan in the interfibrillar matrix around irregularly arranged collagen fibrils.     

Hypocomplementaemic urticarial vasculitis associated with Jaccoud's syndrome

Summary We report a 33-year-old Japanese man diagnosed as having hypocomplementaemic urticarial vasculitis at the age of 21, who subsequently developed Jaccoud's syndrome. Although Jaccoud's syndrome has been most frequently seen in patients with systemic lupus erythemalosus, an association with other diseases has occasionally been described. Jaccoud's syndrome clinically shows joint deformities similar to rheumatoid arthritis, and needs to be differentiated from it. Patients with hypocomplementaemic urticarial vasculitis may develop Jaccoud's syndrome.     

Donepezil‐induced sleep spindle in a patient with dementia with Lewy bodies: a case report

Here, we report a case of rapid eye movement sleep behavioural disorder in an elderly patient with dementia with Lewy bodies. Pretreatment polysomnography revealed atonia during rapid eye movement sleep, absence of sleep spindles and loss of slow‐wave sleep. Administration of donepezil, an acetylcholinesterase inhibitor, markedly improved delusional symptoms and cognitive function. Pretreatment polysomnography performed after donepezil administration revealed a considerable number of sleep spindles. The effects of cholinergic modulation induced by donepezil seemed to cause remarkable improvement in mental status, incorporating associated with sleep spindles generated by the thalamocortical circuit involved in this patient.     

Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection

We previously reported that interferon-gamma (IFN-γ) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureusCowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229±119 pg/ml, P<0.01) and liver cirrhosis (LC) (185±88 pg/ml, P<0.05) than in controls (119±27 pg/ml), while it was decreased during IFN treatment (70±25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-γ production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-γ production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-γ production by some cells.     

Ovarian atypical endometriosis: its close association with malignant epithelial tumours

The incidence of ovarian atypical endometriosis and its association with malignant epithelial tumours in a consecutive series of cases during the period 1987 to 1995 were studied. Atypical glandular changes were observed in four (1.7%) of 255 ovarian endometriosis cases and one patient with ovarian atypical endometriosis developed subsequent endometrioid carcinoma in the abdominal wall. Fifty-four (24.1%) of the 224 ovarian cancers were associated with ovarian endometriosis; 21 with typical and 33 with atypical endometriosis. Clear cell carcinomas and endometrioid carcinomas were most frequently associated with endometriosis, with 54% (27 of 50 cases) and 41.9% (13 of 31), respectively. Atypical endometriosis was found in 18 clear cell carcinomas, in seven endometrioid carcinomas, in four serous carcinomas, in three mucinous borderline tumours, and in one serous borderline tumour. In 13 cases, the atypical endometriosis was in contiguity with malignant epithelial tumours. We consider that atypical endometriosis possesses a precancerous potential or is most frequently associated with clear cell and endometrioid carcinomas. Close screening of cellular atypia or hyperplasia in ovarian endometriosis and careful long-term follow-up of patients with atypical endometriosis is required.     

Histological evaluation of alveolar ridge augmentation using injectable calcium phosphate bone cement in dogs

Summary  Alveolar ridge augmentation is an important procedure to restore tooth loss. Several types of graft materials have been used for augmenting the alveolar ridge. An injectable calcium phosphate cement (CPC) has been applied to periodontal bone defects and has shown favourable results. Thus, this CPC may work as an effective graft material for alveolar ridge augmentation. The aim of this study was to evaluate the effectiveness of the CPC for large-scaled (about 7 × 8 × 6 mm) ridge augmentation in dogs. Alveolar ridge defects were created bilaterally in the maxilla of six beagle dogs. The CPC was applied to one of the bilateral maxillary defects. The untreated defect on the contralateral side served as control. The animals were sacrificed at 6 months after surgery and decalcified histological specimens of the alveolar ridge were prepared histometrically and evaluated under a light microscope. Newly formed and reconstructed alveolar ridges covering the CPC were observed in all experimental sites. In the control sites, only slight newly bone formation was observed. Histomorphometrical analysis indicated that the CPC grafted group exhibited significantly ( P  = 0·0001) increased area and height in new bone formation compared with those of the control group. The results indicate that the CPC appears to be an effective material for alveolar ridge augmentation and may act as a space maintainer to conduct new bone formation.     

Medical management of recurrent aggressive angiomyxoma with gonadotropin-releasing hormone agonist

Patients with aggressive angiomyxoma may experience local recurrences. We report a case of recurrent aggressive angiomyxoma medically treated successfully with a gonadotropin-releasing hormone agonist. A 34-year-old woman with a huge perineal tumor underwent an extensive resection of the abdominoperineal tumor combined with total pelvic exenteration. Histology showed aggressive angiomyxoma and the tumor cells were immunoreactive for estrogen and progesterone receptors. Although the patient had experienced no local recurrence for 12 months under adjuvant therapy with a gonadotropin-releasing hormone agonist, a recurrence occurred 3 months after the completion of adjuvant therapy. The patient underwent medical treatment with a gonadotropin-releasing hormone agonist and had a complete resolution of the recurrent tumor again. Hormonal treatment with a gonadotropin-releasing hormone agonist can be applied for small primary aggressive angiomyxomas in addition to adjuvant therapy for residual tumors.     

A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ? Wafer) for Japanese Patients with Malignant Gliomas

Carmustine (BCNU) implants (Gliadel^® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.     

Improvement of stone comminution by slow delivery rate of shock waves in extracorporeal lithotripsy

AIM: The aim of this study was to investigate the effect of delivery rate of shockwaves (SW) on stone comminution and treatment outcomes in patients with renal and ureteral stones. METHODS: Patients with radio-opaque stones in the upper urinary tract that were treated by extracorporeal shock wave lithotripsy (ESWL) were divided into two groups according to delivery rate (120 or 60 SW/min). The effective fragmentation after one ESWL session and treatment success at 3 months after ESWL was compared between the two groups. RESULTS: Of 134 patients (84 men and 50 women), 68 patients were treated at a fast rate and 66 were treated at a slow rate. Thirty and 38 patients in the fast rate group and 28 and 38 in the slow rate group had renal and ureteral stones, respectively. After one ESWL session, effective fragmentation was noted more often in the slow group (65.2%) than the fast group (47.1%) (P = 0.035), particularly for smaller stones (stone area <100 mm(2)) (P = 0.005) and renal stones (p = 0.005). However, there was no significant difference in treatment success at 3 months after ESWL between the two groups. In univariate logistic regression analysis, slow SW rate and smaller stones were significant factors for effective fragmentation after one ESWL session. In multivariate analysis, slow SW rate and smaller stones were also independent factors. CONCLUSIONS: Slow SW rate contributed to better stone comminution than fast rate, particularly for small stones and renal stones. ESWL treatment at a slow SW rate is recommended to obtain efficient stone fragmentation.     

Successful treatment of chemo-refractory pulmonary metastases of renal pelvic cancer by second-line chemotherapy including gemcitabine followed by salvage surgery

A 51-year-old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.