Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.     

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients.

To investigate the role of the Maillard reaction in the pathogenesis of diabetic complications, we produced several clones of monoclonal antibodies against advanced glycation end products (AGEs) by immunizing mice with AGE-modified keyhole limpet hemocyanin, and found that one clone (AG-1) of the anti-AGE antibodies reacted specifically with imidazolones A and B, novel AGEs. Thus, the imidazolones, which are the reaction products of the guanidino group of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, were found to be common epitopes of AGE-modified proteins produced in vitro. We determined the erythrocyte levels of imidazolone in diabetic patients using ELISA with the monoclonal anti-imidazolone antibody. The imidazolone levels in the erythrocytes of diabetic patients were found to be significantly increased as compared with those of healthy subjects. Then we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in an advanced stage of diabetic nephropathy, as well as in atherosclerotic lesions of aortas. This study first demonstrates the localization of imidazolone in the characteristic lesions of diabetic nephropathy and atherosclerosis. These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis.     

Spontaneous subcapsular hepatic hemorrhage associated with pregnancy: Report of a case

We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver lobes, while extravasation was demonstrated by CO₂ intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication, and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease.     

Effect of carbon dioxide and oxygen on endothelin production by cultured porcine cerebral endothelial cells

We have previously reported the production of endothelin, a potent vasoconstrictor peptide, by porcine cerebral microvessel endothelia and suggested its important role in the regulation of local blood flow within the brain. In our present study, radioimmunoassay with anti-porcine endothelin antiserum revealed that endothelin, produced by cerebral microvessel endothelia grown on a filter, is released mainly to the basement membrane side, not the vascular lumen side. This finding suggests that endothelin constricts arterioles locally where it is produced by endothelia. We also found that cerebral microvessel endothelia produce less endothelin under low oxygen pressure and more endothelin under low carbon dioxide pressure. Our results suggest that endothelin has a role in the regulation of cerebral blood flow in response to oxygen and carbon dioxide pressure.     

Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

We have studied the effect of intrathecal administration of N-methyl-D- aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms). NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01 micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NMDA reversed these decreases in MAC, but not to control values with APV 10 and 30 micrograms and MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.      

Bronchial hyperresponsiveness to acetylcholine during acute pulmonary congestion in guinea pigs]

To understand the precise mechanism of bronchial hyperresponsiveness in patients with congestive heart failure, we studied the effect of mild pulmonary congestion on bronchial responsiveness to inhaled acetylcholine (ACh) in guinea pigs. We induced mild pulmonary congestion by inflation of a balloon placed in the left atrium, and maintained the left atrial pressure (Pla) at 10 mmHg for 30 minutes with continuous monitoring of lung resistance (RL) and dynamic compliance (Cdyn). Furthermore, we determined the provocative concentration of ACh producing 100% increase in RL (PC100-ACh), before and during balloon inflation. In animals with propranolol pretreatment, but not in animals without propranolol pretreatment, mild pulmonary congestion caused slight increase in RL (N.S.) and significant decrease in Cdyn (p less than 0.01) and PC 100-ACh (p less than 0.01). Cutting of bilateral vagal nerves partially inhibited the decrease of PC100-ACh, but pretreatment with either phenoxybenzamine, indomethacin, AA-861 or OKY-046 had not effect. These results suggest that blockade of beta-adrenergic receptors and the vagal reflex, but not of alpha-adrenergic receptors or arachidonates, contributes to bronchial hyperresponsiveness during acute pulmonary congestion.     

Leukocytosis and low serum IgA in workers exposed to the epoxy compound,t-methyl-3-phenylglycidate

Summary Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varing degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.     

Effects of dilevalol,an R,R-isomer of labetalol,on blood pressure and renal function in patients with mild-to-moderate essential hypertension

Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new -adrenoceptor blocker with ₂-receptor stimulating and -recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks.Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study.Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA.The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.