A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Clinical features of Japanese children and adolescents with systemic lupus erythematosus: Results of 1980–1994 survey

Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period. Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.     

Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans

Background and objective: Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO. Methods: SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model. Results: The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF‐α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high‐level TNF‐α production from monocytes of patients with SA‐induced BO. Conclusions: These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.     

Limitations of endoscopic haemostasis by ethanol injection and surgical management for bleeding peptic ulcer

Abstract Two hundred and fifty-three patients with bleeding peptic ulcer underwent therapeutic endoscopy using local ethanol injection and were evaluated to determine the need for surgery and outcome. Permanent endoscopic haemostasis was achieved in 178 (70.4%) cases. Pulsatile arterial bleeding in ulcers and shock on admission (respectively, P < 0.01, P < 0.05) were significantly more frequent in patients with unsuccessful endoscopic treatment. Postoperative stay was significantly longer ( P < 0.05) for patients with bleeding peptic ulcer than for patients requiring surgery for intractable ulcer without bleeding. Surgery was recommended if three attempts at endoscopic treatment did not achieve permanent haemostasis. The need for more than three such treatment sessions and the presence of a large excavated ulcer with an exposed vessel in an elderly patient were considered to indicate the necessity for surgery. Surgical procedures to which the operator is accustomed and intensive management were recommended for emergency cases to optimize the likelihood of survival.     

Heart Rate Variability in Patients with Familial Amyloid Polyneuropathy

The purpose of this study was to evaluate heart rate variability (HRV) in patients with familial amyloid polyneuropathy (FAP) using the time- and frequency-domain analysis. The study population consisted of 19 patients with FAP, and 19 age and sex matched normal volunteers. The 24-hour Holter recordings of all subjects in sinus rhythm and off medication were analyzed. Five time-domain indices of HRV were computed. The frequency component of HRV was calculated by fast Fourier transform analysis of the RR intervals. The power spectrum of the low frequency (LF) between 0.04–0.15 Hz and high frequency (HF) between 0.15–0.40 Hz and the LF/HF ratio was calculated. Global measures of HRV including the standard deviation of the mean of RR intervals (SDNN) and the standard deviation of 5-minute mean RR intervals (SDANN) were decreased in patients with FAP. Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (pNN50) and the HF power on spectral analysis were less in patients with FAP. LF power and LF/HF ratio were more decreased in patients with FAP at the advanced stage than at the early stage. In conclusion, HRV was significantly decreased in patients with FAP at the early stage, and sympathetic activity was more decreased in patients at the advanced stage. These findings suggest that the decrease of the HRV is an indicator of this disease and the power spectral analysis of the HRV is beneficial in assessing the severity of the autonomic dysfunction.     

Urothelial carcinoma (clear cell variant) diagnosed with useful immunohistochemistry stain

The case is reported of urothelial carcinoma (clear cell variant) that was diagnosed with useful immunohistochemistry stain. A 70-year-old man, who had undergone left radical nephrectomy for renal cell carcinoma in August 2003 and partial lobectomy for pulmonary metastasis in May 2005, complained of hematuria in June 2005. On evaluation, a papillary pedunculated tumor was detected in the left wall of the urinary bladder. A transurethral resection of the bladder tumor (TUR-Bt) was performed in July 2005. The pathological diagnosis was difficult due to diffuse clear cell appearance. Immunohistochemistry stain showed urothelial carcinoma, not metastasis of the renal cell carcinoma. Finally it was diagnosed as urothelial carcinoma clear cell variant. Urothelial carcinoma has many variants that show a variety of appearances and characteristics. These should be well known before medical therapy is initiated.