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.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Cerebral aspergillosis after burr-hole surgery for chronic subdural hematoma: case report

We report a case of aspergillosis in the subdural space and frontal lobe in an 83-year-old man. The clinical course simulated that of a brain tumor. The source for the infection was considered to be the previous burr-hole surgery for chronic subdural hematoma, which was performed 2.5 years before the onset of symptoms. The patient was treated by removal of the abscess and granuloma. The clinical features and treatment of aspergillosis after neurosurgical procedures are discussed.     

Clinical studies on a newly devised amino acid solution for neonates

In 97 neonates receiving total parenteral nutrition in the postoperative period, clinical assessment was made for a newly devised amino acid solution (PF-I-III) from the standpoint of plasma amino acid profile and nutritional effect. These amino acid solutions prepared are characterized by the high concentration of branched-chain amino acids up to 40%, increased arginine and decreased glycine, phenylalanine and methionine as compared with commercially available solutions. In the PF group, each amino acid was kept within the range of standard value. Correlation between plasma amino acid profiles and the dose of each amino acid administered was obtained, from which minimum, standard, and maximum doses for each amino acid was determined. Based on these values, we proposed new formula for neonates which elicits no abnormal plasma amino acid pattern even when amino acids are administered at the dosage level of 1.5-2.5 g/kg/day.     

Musculocutaneous grafts with draining vein: an experimental study

Venous drainage of a musculocutaneous graft was shown to be of importance for the prevention of necrosis and successful graft take. An experimental model was provided in which the iliolumbar veins were used as draining veins in creating musculocutaneous grafts 4 X 3 cm and 4 X 6 cm in size. In the study, it was demonstrated that necrosis could be prevented by preserving draining veins. The number and size of these veins were of some significance in the survival of the grafts.     

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     

An Experimental Study on the Relationship Between Artificial Korotkoff Sounds and Self-Excited Oscillation Using a Circulatory Simulator

In the medical field, Korotkoff sounds have been explained as sounds generated by the disturbed blood flow in the artery. However, in the biomechanics field, Korotkoff sounds are considered to be produced and/or modified by the self-excited oscillation of a collapsed artery. The self-excited oscillation is an oscillation of the arterial wall. In addition, it is influenced by the nonlinear pressure–flow relationships in the artery and the arterial compliance. In this paper, we proposed an arterial-compliance-measuring method, using Korotkoff sounds. We constructed a circulatory simulator with a brachial model that mimics the physiological circulation, because in vivo resolution of nonlinear pressure–flow relationships is very difficult. The simulator was utilized to generate artificial Korotkoff sounds similar to those in auscultation in the brachial model. Additionally, we prepared latex tubes as artificial brachial arteries. In the experiment, we investigated the relationship between the self-excited oscillation and Korotkoff sounds by the distinguishing its frequency characteristics. The frequency of the sounds was changed by the variation of the tube compliance. As a result, we have found that the changes of the sounds largely depended on the difference of the tube compliance in this simulator. In conclusion, Korotkoff sounds contain useful information for predicting brachial arterial compliance. These experiments indicate the effectiveness of noninvasive measurement for brachial arterial compliance using Korotkoff sounds.     

Continuous measurement of oxygen consumption using the reversed fick method

We developed a continuous oxygen consumption (Vo₂) measurement system employed the reversed Fick method, in which Vo₂ in computed from continuously measured sured arterial and mixed venous oxygen saturation assed by pulse oximetry and mixed venous oximetry, respectively, and cardiac output by the heat deprivation technique. This system was compared with the conventional intermittent reversed fick method in 7 patients during surgery and with indirect calorimetry in 4 intensive care unit (ICU) patients. The Vo₂ measured by the continuous reversed Fick method showed a high correlation with those simultaneously measured by the intermittent Fick method (r=0.97,P<0.01) and by indirect calorimetry (r=0.74,P<0.01). The 95% confidence limits (bias±2 SD) of the continuous reversed Fick method were −0.6±45 ml·min⁻¹ with the intermittent Fick method and −31±56 ml·min⁻¹ with indirect calorimetry. The continuous Fick method is in satisfactory agreement with the conventional methods for the measured of Vo₂ and potentially allows for convenient assessment of Vo₂ in critically ill patients. This study was supported in part by Grants-in-Aid for the Encouragement of Young Scientists 01771185 and 04857171 from the Ministry of Education, Science and Culture of Japan     

Restricted diversity of the variable region nucleotide sequences of the heavy and light chains of a human rheumatoid factor

The complete nucleotide sequences of the variable region genes of the heavy and light polypeptide chains of a human monoclonal rheumatoid factor (RF) produced from a human-mouse heterohybridoma were determined. The antibody, designated YES8c, contained V kappa III, J kappa 2, VH1, JH4, and a D gene segment of 9 amino acids. The nucleotide sequences and the deduced amino acid sequences of the light chain variable region were remarkably homologous (97-98%) to previously described RF of the Wa idiotypic family (PAY, GLO, CUR, FLO, and GAR) and to that of a V kappa III germline gene (Humkv325). The YES8c heavy chain variable region gene was most closely related to the VH1 gene of the restricted human fetal repertoire, designated 51p1, and also to 3 rearranged VH1 genes that were recently isolated from patients with chronic lymphocytic leukemia. These results suggest that variable region genes of RFs are highly conserved and that YES8c VH, as well as V kappa, may be identical to heavy and light chains expressed during early B cell development.