Antioxidant status and lipid peroxidation in diabetic rats under hyperbaric oxygen exposure.

Hyperglycemia is known to cause oxidative stress that leads mainly to enhanced production of mitochondrial reactive oxygen species (ROS). It has been demonstrated that hyperbaric oxygen (HBO) treatment also increases the formation of ROS. There are, however, no comprehensive evaluations of such oxidative effects in diabetes which requires HBO treatment. The purpose of this study is to investigate the influence of a clinically-recommended HBO treatment on glucose homeostasis and oxidative stress in rats with streptozotocin (STZ)-induced diabetes. Under the clinically-used HBO exposure protocol, the levels of blood glucose, thiobarbituric acid reactive substances (TBARS) as a lipid peroxidation marker, and the activity of superoxide dismutase (SOD) as an antioxidant enzyme marker were investigated in the erythrocytes, liver, pancreas, skeletal muscle, and brain of rats with STZ induced diabetes. The levels of blood glucose and TBARS increased significantly (p<0.05), and the activity of SOD decreased significantly (p<0.05) in the erythrocytes and all organs of rats with diabetes subjected to HBO exposure. These results suggested that HBO exposure might boost glucose autoxidation and increase ROS production in STZ-induced diabetes as side-effects of administering HBO treatment for the first time.

Malignant amelanotic melanoma of the middle ear.

We report the first case (to our knowledge) of malignant melanoma of amelanotic type arising from the mucosa of the middle ear. An 81-year-old man who presented with right hearing loss was diagnosed as having otitis media with effusion at an otolarygology clinic. Despite subsequent treatment, he developed otorrhea and otalgia. Furthermore, a granular mass was found in the pars flaccida of the tympanic membrane. A biopsy of the mass was performed, and the findings were suggestive of malignant melanoma. The disease was already in an advanced stage, because metastases were noted in the patient's lungs and liver. Although chemohormonal therapy was performed and was slightly effective in reducing the primary tumor, the patient died of acute renal failure. Autopsy confirmed the diagnosis of amelanotic melanoma of the middle ear.

Selective migration of alpha-smooth muscle actin-positive myofibroblasts toward fibronectin in the Boyden's blindwell chamber.

1. In order to address the hypothesis that migrating fibroblasts have a different phenotype, human fetal lung fibroblasts (HFL-1) cells were evaluated in the Boyden blindwell chamber migration assay followed by immunoelectron microscopy. 2. HFL-1 cells were placed on nucleopore filters and incubated for 2 h using purified human plasma fibronectin (pFn) as a chemoattractant. Filters were then processed for immunoelectron microscopy using antibodies for alpha-smooth muscle (alpha-SM) actin as a marker for myofibroblasts, cellular fibronectin (cFn) and VLA-5. 3. Cells which had migrated to the bottom side of the filter were more likely to express alpha-SM actin, 29.1 +/- 3.4% of cells, compared with cells which did not migrate through the filter, 12.4 +/- 1.3% (P < 0.05). The total proportion of alpha-SM-actin-positive cells located on both sides of the filter showed no difference between those which had migrated toward pFn and controls (17.7 +/- 1.0% compared with 20.2 +/- 2.5%). 4. cFn-positive cells showed minimal differences compared with control cells, while perinuclear and endoplasmic reticulum staining of VLA-5 was observed only in the cells treated with pFn. 5. The results show that HFL-1 cells are heterogenous for alpha-SM actin expression. Short-term incubation with pFn did not change the proportion of alpha-SM-actin-positive HFL-1 cells. Cells which migrate, however, are enriched for alpha-SM actin expression. pFn-induced fibroblast chemotaxis can selectively recruit myofibroblasts with increased alpha-SM actin expression, a feature which may contribute to the altered population of cells at sites of fibrosis.

Dynamics of the expression of cytoskeleton components and adherens molecules by fibroblastic cells in alkali-burned and lacerated corneas.

To provide a better understanding of the role of fibroblastic cells during corneal wound-healing, we examined the expression of cytoskeleton components (i.e. smooth muscle alpha-actin (alpha-SMA), vimentin, desmin), adherens molecules (vinculin and talin) and cellular fibronectin in alkali-burned and lacerated rabbit corneas. Alkali-burned and lacerated corneas, which had healed for various periods of time (1 day to 45 days), were excised and subjected to immunohistochemical studies with monoclonal antibodies against alpha-SMA, vimentin, desmin, vinculin, talin and cellular fibronectin. Monoclonal antibody against alpha-SMA reacted with fibroblastic cells in injured corneas but did not react with keratocytes in normal corneas. Anti-desmin antibody did not react with any corneal cells in normal or injured corneas except the muscle cells in the newly-formed capillary of injured corneas. The results indicate that the fibroblastic cells in injured corneas have the characteristics of myofibroblasts. The number of myofibroblasts in granulation tissues increased and peaked within 3 weeks of injury and then declined. Electron microscopy revealed that some fibroblastic cells in the lacerated cornea which had healed for 4 weeks contained dense chromatins. In situ 3'-end labeling with terminal nucleotide transferase indicating that some of the fibroblastic cells contained nicked genomic DNA. These observations imply that apoptosis plays a role in regulating the number of myofibroblasts in the injured corneas. Antibodies against cellular fibronectin, vinculin and talin react with the fibroblastic cells in the injured corneas, but not with the keratocytes of normal corneas. Examination with transmission electron microscopy demonstrated the presence of microtendon and fibronexis associated with fibroblastic cells and the presence of stress fiber within fibroblastic cells. The results indicate that the fibroblastic cells may cause corneal wound contraction, which in turn contributes to the formation of opaque scar tissues.

Fuzzy and conventional control of high-frequency ventilation.

A high-frequency ventilator was developed, consisting of a single-phase induction motor, an unbalanced mass and a mechanical vibration system. Intermittent positive pressure respiration was combined with high-frequency ventilation to measure end-tidal pCO2. Hysteresis was observed between the rotational frequency of the high-frequency ventilator and end-tidal pCO2. A fuzzy proportional plus integral control system, designed on the basis of the static characteristics of the controlled system and a knowledge of respiratory physiology, successfully regulated end-tidal pCO2. The characteristics of gas exchange under high-frequency ventilation was approximated by a first-order linear model. A conventional PI control system, designed on the basis of the approximated model, regulated end-tidal pCO2 with a performance similar to that of the fuzzy PI control system. The design of the fuzzy control system required less knowledge about the controlled system than that of the conventional control system.

Duration and extent of antianginal effects of a sustained-release formulation of nifedipine in angina.

Twenty-four patients with chronic stable exertional angina pectoris were randomized in a double-blind, placebo-controlled, crossover trial to assess the efficacy and durability of a newly developed, sustained-release formulation of nifedipine (nifedipine CC) in a single 40-mg oral dose. Symptom-limited graded treadmill exercise tests were performed just before, and at 4, 7, and 24 h after a single administration of the drug or the placebo was given. Exercise tolerance at 4, 7, and 24 h after the drug were compared with the corresponding placebo values. Data could be analysed for 19 patients. Maximal exercise time, time to the onset of angina, and time to 1 mm ST segment placebo. The average maximal exercise time was significantly increased by 72, 76, and 37 s at 4, 7, and 24 h. Rate-pressure product at rest and at peak exercise showed significant changes only at 24 h compared with placebo (both P < 0.05). The maximal increase in exercise tolerance was most marked at 7 h nifedipine CC, at which time plasma drug concentration was 99.4 +/- 14.0 ng.ml-1. Thus, in patients with chronic stable exertional angina pectoris, nifedipine CC showed a prolonged improvement in exercise tolerance up to 24 h after a single oral administration.

Effect of antianginal agents on the relationship between rate-pressure product and myocardial oxygen uptake.

To evaluate the effects of antianginal agents on the correlation between rate-pressure product and myocardial oxygen uptake, multistage supine leg exercise tests were performed by 21 patients with stable effort-induced angina pectoris before and after administration of antianginal drugs (a calcium channel blocker of the dihydropyridine class [10 mg of nisoldipine orally] in 11 patients and a beta-blocker [0.2 mg/kg of propranolol intravenously] in 10 patients). The rate-pressure product was closely correlated with myocardial oxygen uptake before and after administration of each drug. However, the slope of the regression line of rate-pressure product (X) and myocardial oxygen uptake (Y) became significantly steeper after the calcium channel blocker administration, and the Y-intercept was significantly increased by administration of the beta-blocker. Myocardial oxygen uptake was increased after administration of the calcium channel blocker and the beta-blocker compared with control values at corresponding rate-pressure product. These observations should be considered when the rate-pressure product is used to predict myocardial oxygen uptake in patients with angina pectoris who are receiving antianginal drugs.

Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease.

To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic mechanisms of the antianginal action of a novel vasodilator FK409 in dynamic exercise-induced angina.

FK409 is a novel vasodilator with a unique chemical structure. We wished to elucidate the mechanisms of antianginal action of FK409 in dynamic exercise-induced angina. Twelve patients with stable effort angina pectoris were studied before and after a single 40-mg oral dose of FK409. Chest pain was induced in all of 12 patients during the control multistage bicycle ergometer exercise. After FK409 administration, the same workload did not induce chest pain in 6 patients. The ST segment at peak exercise showed less severe depression from 0.15 +/- 0.02 to 0.05 +/- 0.01 mV (p < 0.001). Left ventricular (LV) filling estimated by the Doppler method was reduced, and pulmonary artery wedge pressure decreased significantly (p < 0.001) throughout exercise testing after FK409. Myocardial oxygen uptake and coronary sinus flow throughout exercise testing decreased significantly (p < 0.05) after FK409 administration. The results of the present study demonstrate that decrease in myocardial oxygen demand may be caused by pre- and afterload reduction and that it could be a major mechanism of the antianginal action of FK409. However, other mechanisms such as redistribution of coronary blood flow to the subendocardium, direct dilatation of the stenotic parts of the epicardial arteries, and an increase in collateral blood flow should be considered additional possible mechanisms of the antianginal action of FK409.

Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris.

We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise.

Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease.

To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease.

Mechanism of abnormal postexercise systolic blood pressure response and its diagnostic value in patients with coronary artery disease.

To define the factors that affect an abnormal postexercise systolic blood pressure (SBP) response and to verify the diagnostic value of that response in patients with coronary artery disease (CAD), we studied 33 normal subjects, eight patients with hypertension who had no CAD, and 42 patients with documented CAD who underwent supine leg exercise testing. SBP recovery ratios were derived by dividing the values obtained 1 and 3 minutes after exercise by the peak value. The upper normal limit of the SBP ratio was defined by two standard deviations from the mean for 33 normal subjects. The specificity of this criterion for identifying patients with CAD was 97% and the sensitivity was 60%. None of the eight patients with hypertension showed an abnormal postexercise SBP response. At peak exercise the pulmonary artery wedge pressure was significantly greater in the patients with CAD having an abnormal response. In multiple regression analysis the exercise pulmonary artery wedge pressure, the exercise SBP, and the systemic vascular resistance after exercise were determining factors for an abnormal SBP response. Three-vessel disease was more common in patients with an abnormal response. Results of this study indicate that an abnormal postexercise SBP response appears to be determined by (1) the extent of exercise-induced impairment of left ventricular function and (2) peripheral vascular tone during recovery. This study also suggests that this criterion can increase the specificity of supine exercise testing in patients with CAD including those with hypertension and might provide a marker for the severity of impaired left ventricular function by exercise in CAD.

Prediction of left ventricular function during supine bicycle ergometer exercise in angina-free patients with old myocardial infarction.

We investigated whether or not left ventricular function during dynamic exercise in angina-free patients with old myocardial infarction could be estimated using resting left ventricular function and noninvasive parameters determined during exercise. We studied 70 patients with old myocardial infarction by measuring hemodynamic parameters during supine multistage bicycle ergometer exercise. Coronary arteriography and left ventriculography were performed: then the left ventricular ejection fraction and left ventricular end-diastolic volume were measured. The parametric changes (delta) between rest and peak exercise were determined. Significant positive correlations were observed between cardiac index (CI) at rest and at peak exercise (r = 0.62, p less than 0.001), as well as between pulmonary artery wedge pressure (PAWP) at rest and at peak exercise (r = 0.72, p less than 0.001). Multiple regression analysis indicated that CI and PAWP at peak exercise as dependent variables were best described by the equations: CI at peak exercise = 1.074 [CIrest] +0.031 [delta HR] + 0.004 [ExD] + 0.018 [LVEF] - 1.560 (r = 0.79, p less than 0.001), PAWP at peak exercise = 0.994 [PAWPrest] - 0.181 [LVEF] + 0.203 [delta DBP] -0.076 [delta HR] -21.488 (r = 0.80, p less than 0.001). These data suggested that CI and PAWP during dynamic exercise in angina-free patients with old myocardial infarction could be predicted using noninvasive parameters, such as increments of blood pressure and heart rate as well as exercise duration, together with data on resting left ventricular function, such as resting CI, resting PAWP, and resting left ventricular ejection fraction (LVEF).

Hemodynamic mechanisms of antianginal action of calcium channel blocker nisoldipine in dynamic exercise-induced angina.

To investigate the mechanism of antianginal action of the calcium channel blocker nisoldipine and to determine the reproducibility of the clinical and hemodynamic events induced by supine leg exercise, 30 patients with stable effort angina pectoris were studied. They were divided into two groups; one group of 19 patients received a single 10-mg dose of nisoldipine orally, and the other group of 11 patients received a single dose of placebo orally. Chest pain was induced in all of 30 patients during the control exercise test. After nisoldipine administration, chest pain was not induced in 13 of 19 patients and was of lessened severity in five patients with the same work load as those performing control exercise. ST segment at peak exercise showed less severe depression after nisoldipine. Systemic vascular resistance was reduced by 38% (p less than 0.001) at rest and 22% (p less than 0.001) at peak exercise, and coronary vascular resistance was reduced by 31% (p less than 0.01) at rest and 18% (p less than 0.01) at peak exercise. Pulmonary artery wedge pressure fell from 6 +/- 1 to 3 +/- 1 mm Hg (p less than 0.001) at rest and from 28 +/- 3 to 11 +/- 2 mm Hg (p less than 0.001) at peak exercise. Coronary sinus flow at rest and myocardial oxygen uptake both at rest and during exercise was not modified by nisoldipine. However, coronary sinus flow at peak exercise increased significantly from 219 +/- 24 to 249 +/- 31 ml/min (p less than 0.01) after nisoldipine, and myocardial oxygen uptake was not significantly changed despite decreased coronary vascular resistance. The clinical and hemodynamic events induced by the exercise during invasive studies (except pulmonary artery wedge pressure at rest) were reproducible after placebo administration. Our data demonstrate that increased coronary blood flow could be the major mechanism of the antianginal action of nisoldipine in supine leg exercise-induced angina.

New therapeutic approach to aortic dissection complicated by cardiac tamponade.

The management of aortic dissection with cardiac tamponade may result in increased blood pressure and thereby itself make the aortic dissection worse. Nevertheless, it is important to prevent cardiac failure caused by cardiac tamponade. We describe a case of aortic dissection with cardiac tamponade. Echocardiography and aortography showed DeBakey IIIb-type aortic dissection with retrograde dissection, complicated by cardiac tamponade and aortic insufficiency. To treat this condition, a new therapeutic approach was undertaken. A vasodilator was administered, then pericardiocentesis guided by echocardiography was performed. To prevent abrupt elevation of blood pressure in response to the relief of cardiac tamponade, the pericardial aspiration was carried out slowly--it took four hours for the complete drainage of 415 ml of blood--and a vasodilator, sodium nitroprusside, was administered. After drainage, cardiac function was reversed fully, and the systolic pressure was controlled under 140 mmHg. Then, using extra-corporeal circulation, the surgical procedure was performed successfully. We conclude that it is useful to treat cardiac tamponade by controlling blood pressure with slow drainage and use of a vasodilator in preparation for performing the surgical procedure.

[An autopsy case of malignant lymphoma of the pancreas].

Case reports of malignant lymphoma of the pancreas are extremely rare. We experienced a 36-year-old man with malignant lymphoma involving the pancreas associated with obstructive jaundice, confirmed by autopsy. It is very difficult to differentiate between pancreatic carcinoma and pancreatic malignant lymphoma. Age, icterus, diffuse pancreatic enlargement, pathological findings and tumor markers may be useful in suggesting lymphoma. Trials of positive biopsy, appropriate radiotherapy and chemotherapy are necessary in patients who may have malignant lymphoma of the pancreas.