Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

Airway troubles related to the double-lumen endobronchial tube in thoracic surgery

Purpose Several case reports indicate critical respiratory complications in relation to the double-lumen endobronchial tube (DLT). A prospective survey for the airway problems in using the DLT is presented. Methods One hundred adult patients undergoing thoracotomy for lung cancer were investigated. Tube malposition and airway obstruction were searched using a fiber-optic scope. The endobronchial cuff was positioned just below the trachcal carina while the trachea was intubated with a DLT (Rüsch). The distances of displacement, from the tracheal carina to the bronchial cuff, were measured during anesthesia using an epidural catheter, which had marks every 5 mm. The distances for correcting the tube position were measured at both the bronchial cuff and the level of the teethPaO₂,PaCO₂ andSPO₂ were also measured. Results Malposition (displacement over 5 mm from the correct position) was found in 42 patients, and 40 of them were in a withdrawal direction, occurring at the postural change and during one-lung ventilation, especially during manipulation of the lung hilum. Correcting distances at the level of the teeth were 15.3–3-times longer than those at the bronchial cuff. Airway deformities and gradual withdrawal of the bronchial cuff were found in association with surgical manipulation. Obstruction occurred at the tips of the tracheal tube in four patients and the bronchial tube in six patients, and at the tip of both in two patients. Hypoxemia (PaO₂<60 mmHg) occurred in four patients and hypercapnea (PaCO₂>60 mm Hg) in two patients. Conclusion Most of the DLT obstructions were associated with withdrawal malposition. Great attention to DLT displacement and airway deformity is advised.     

Jejunal carcinoma with adenoma —Report of a case and review of the Japanese literature—

A rare case of jejunal carcinoma coexisting with adenoma, situated 120 cm distal to the ligament of Treitz in a 53 year old male, is reported herein. We also review cases of adenoma and carcinoma in the jejunum and ileum from the Japanese literature, and discuss the histogenesis of carcinoma of the jejunum and ileum.     

A case of congenital antithrombin II deficiency with pulmonary infarction

A 48-year-old woman was admitted because of increased bloody sputum. Since she had had a history of repeated thrombotic episodes including venous thrombosis in the lower limbs (21 year old) and pulmonary emboli developing into pulmonary infarction (41 years old), the patient was treated with anti-coagulant therapy using Warfarin for 7 years. Warfarin was discontinued after admission and heparin was administered instead at a relatively low dose of 5,000 units daily, resulting in a considerable diminution of hemoptysis. Unfortunately however, it caused a relapse of active thrombosis associated not only with a significant increase of the product of fibrinolysis (FDP), LDH and GOT but with a concomitant decrease of the platelet count. Hematological examinations concerning coagulation and fibrinolysis remained within a normal range except for the serum concentration of antithrombin III (AT III) and its functional property with regard to the heparin cofactor, which were 8.8 mg/dl and 48%, respectively. Since the findings were consistent with congenital deficiency of AT III, some members of her family were also examined. The concentration of AT III and its activity in the patient's son and her daughter deteriorated in a similar manner, indicating that this was a definite case of congenital deficiency of AT III. The clinical manifestations of 87 cases with congenital AT III deficiency, belonging to 24 families reported in Japan were reviewed.     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

GLUCOCORTICOID-UNRESPONSIVE FEVER IN A PATIENT WITH WEBER-CHRISTIAN DISEASE

SUMMARY Weber-Christian disease, a disease of unknown aetiology, is characterised by relapsing febrile episodes and systemic panniculitis. Glucocorticoid therapy is often useful during acute phases of the disease. This report describes a patient in whom hyperpyrexia did not respond to high-dose glucocorticoid treatment, yet did respond to a non-steroidal anti-inflammatory drug (NSAID).