Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Feasibility trial for adjuvant chemotherapy with docetaxel plus cisplatin followed by single agent long-term administration of S-1 chemotherapy in patients with completely resected non-small cell lung cancer: Thoracic Oncology Research Group Study 0809.

BACKGROUND: We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II-IIIA non-small cell lung cancer. METHODS: Patients received three cycles of docetaxel (60 mg m(-2)) plus cisplatin (80 mg m(-2)) and then received S-1 (40 mg m(-2) twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients. RESULTS: One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%). CONCLUSION: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance.

Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice.

OBJECTIVE: To clarify the effect of prolonged feeding of a high-fat and sucrose, and to clarify the effect of sucrose instead of other carbohydrate on obesity and immunity in C57BL/6J mice. METHODS: We investigated the development of obesity and immune cell function in four groups of mice fed high-fat, high-fat plus high-sucrose, high-sucrose, and control diet for 7 months. RESULTS: Mice fed high-fat and high-fat plus high-sucrose groups developed severe obesity. Body weight, adipose tissue weight, serum leptin, blood glucose, and insulin were significantly higher, while the level of serum soluble leptin receptor was significantly lower in mice fed high-fat and high-fat plus high-sucrose diets than in mice fed the control or high-sucrose diets. Splenocyte proliferation stimulated by T-cell mitogen (PHA, ConA, and anti-CD 3 antibody) and B-cell mitogen (LPS) was significantly lower in both obese, high-fat and high-fat plus high-sucrose groups than in control and high-sucrose groups. However, these parameters did not differ between high-fat and high-fat plus high-sucrose groups. CONCLUSIONS: Long-term feeding of high-fat diet and high-fat plus high-sucrose diet similarly induced severe obesity in C57BL/6J mice. Not only T-cell, but also B-cell function may be impaired in mice made severely obese by the high-fat or high-fat plus high-sucrose diets.

Dynamic articulatory model based on multidimensional invariant-feature task representation.

A dynamic model of articulatory movements is introduced. The research presented herein focuses on the method of representing the phonemic tasks, i.e., phoneme-specific articulatory targets. Phonemic tasks in our model are formally defined using invariant features of articulatory posture. The invariant features used in the model are characterized by the linear transformation of articulatory variables and found using a statistical analysis of measured articulatory movements, in which the articulatory features with minimum variability are taken to be the invariant features. Articulatory movements making vocal-tract constrictions or relative movements among articulators reflecting task-sharing structures are typical examples of the features found to have low variability. In the trajectory formation of articulatory movements, the dimension number of the phonemic task is set at a smaller value than that of articulatory variables. Consequently, the kinematic states of the articulators are partly constrained at given time instants by a sequence of phonemic tasks, and there remain unconstrained degrees of freedom of articulatory variables. Articulatory movements are determined so that they simultaneously satisfy given phonemic tasks and dynamic smoothness constraints. The dynamic smoothness constraints coupled with the underspecified phonemic targets allow our model to explain contextual articulatory variability using context-independent phonemic tasks. Finally, the capability of the model for predicting actual articulatory movements is quantitatively investigated using empirical articulatory data.

Identification and clearance involved in the formation of glucuronides of RT-3003, a new peripheral blood flow enhancer, and its metabolite in rats.

Glucuronides of RT-3003 and its metabolite (9-OH-RT-3003), which was hydroxylated at the 9 position on the benzene ring, were separated by HPLC and identified by liquid chromatography (LC)/MS/MS and NMR. The conjugation sites of these glucuronides were determined by nuclear Overhauser effects (NOE) irradiation; RT-3003 was conjugated at an alcoholic hydroxyl group of the hydroxymethyl moiety, and 9-OH-RT-3003 at a phenolic hydroxyl group on a benzene ring and at an alcoholic hydroxyl group of a hydroxymethyl moiety. On a reversed-phase HPLC of 9-OH-RT-3003, alcoholic glucuronide was eluted later than phenolic glucuronide, indicating the high hydrophobicity of alcoholic glucuronide. Clearance for the glucuronidation (ClG) of RT-3003 was lower than the summation of ClG for two types of glucuronidation of 9-OH-RT-3003. ClG of 9-OH-RT-3003 was high in phenolic glucuronide. The activity of UDP-glucuronyltransferase (UDPGT) for RT-3003 was 9.63 times that for 9-OH-RT-3003, and the activity ratio of the two types of glucuronidation of 9-OH-RT-3003 was similar to the ratio of the corresponding ClG. The difference between ClG and UDPGT activity is discussed in association with clearance for the hydroxylation and interaction of substrates with UDPGT.

[A case of pulmonary eosinophilic granuloma undergoing spontaneous remission].

A case of pulmonary eosinophilic granuloma that underwent spontaneous remission is presented. A 23-year old man presented with dry cough and fever. Chest X-ray film revealed diffuse reticulo-nodular infiltrates in the middle and upper lung fields. Chest CT and HRCT showed multiple cystic lesions with thick walls and small nodules predominantly in the inner zone. Based on radiographic findings, pulmonary eosinophilic granuloma was suspected. Bronchoalveolar lavage cell data showed lymphocyte and eosinophil alveolitis with no increase of CD 1 lymphocytes. The symptoms and radiographic findings improved markedly within 4 months after the onset of symptoms without treatment and upon cessation of smoking. Chest CT and HRCT showed that the cystic walls were thinner and that the small nodules had decreased. Thoracoscopic lung biopsy revealed granulomatous lesions consisting of CD 1 and S-100 protein positive histiocytes with infiltration of eosinophils and fibrous lesions. Pulmonary eosinophilic granuloma was diagnosed. There has been no recurrence for 1 year.

In vitro method for assessing hepatic drug metabolism.

We investigated an in vitro metabolic test using rat liver biopsy samples by TLC-autoradioluminography (ARLG), with a view to developing a method to rapidly assess the drug metabolizing activities of individual patients. Drug metabolizing activity was measured in liver biopsy samples collected from rats in four groups: a female control group, male control group, phenobarbital (PB)-administered male group and cimetidine (CM)-administered male group. The productivity of metabolites of 7-ethoxycoumarin (7-EC), debrisoquine (DB) and diazepam (DZ), respectively, was lower in the female control group than in the male control group, but there were no differences in the productivity of metabolites of 5-fluorouracil (5-FU) and tolbutamide (TB), respectively, between the male and female control groups. Those of 7-EC, TB and DZ were higher in the PB-administered group than in the male control group, but those of DB did not differ between these two groups. Those of 5-FU, 7-EC, TB, DB and DZ were lower in the CM-administered group than in the male control group. Using TLC-ARLG, we could detect drug metabolites in rat liver biopsy samples in a relatively short time span at low concentrations similar to those in vivo. We could also measure drug metabolizing activity in cases with and without the involvement of cytochrome P450. When applied in clinical metabolic tests, TLC-ARLG is expected to be useful for assessing the drug metabolizing activities of patients.

A sustained increase in beta-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy.

Effects of long-term therapy with beta 1-selective antagonists (metoprolol, bisoprolol) on beta-adrenoceptors in lymphocytes of patients with idiopathic dilated cardiomyopathy (DCM) were examined. There was a significant reduction in the number of lymphocyte beta-adrenoceptors in patients with DCM compared to that in healthy volunteers, as demonstrated by a selective decrease in maximum number of binding sites (Bmax) for (-)-[125I]iodocyanopindolol (CYP). A therapy with metoprolol and bisoprolol in these patients caused a marked increase in lymphocyte beta-adrenoceptor density. The significant increase was observed from 2 or 3 months after the start of therapy with these drugs, and it was maintained during the therapy for 24 months. The left ventricular ejection fraction in patients with DCM was improved by the long-term therapy with metoprolol and bisoprolol, and this effect seems to be correlated with an observed enhancement of lymphocyte beta-adrenoceptors in the time course. Also, the increase in lymphocyte beta-adrenoceptors appears to be correlated with a gradual amelioration in circulating catecholamine levels by the long-term therapy with beta-adrenoceptor antagonists in patients with DCM. Thus, the present study suggests that beta-adrenoceptors in lymphocytes of patients with DCM are up-regulated by a long-term therapy with metoprolol and bisoprolol.

Effects of phenylephrine on the contractile tension and cytosolic Ca2+ level in rat anococcygeus muscle.

A contractile property of phenylephrine (PE), alpha 1 agonist, on rat anococcygeus muscle was compared with that on rat aorta by simultaneously measuring changes in intracellular Ca2+ ([Ca2+]i) level and muscle tension. (1) PE (0.1-30 microM) and high K+ induced a sustained increases in [Ca2+]i level and muscle tension of both the muscles. (2) An application of verapamil (10 microM) and EGTA (4 mM) decreased the PE- or high K(+)-increased tension and [Ca2+]i level in both the muscle, respectively. (3) A cumulative application of PE or high K+ to anococcygeus muscle and aorta exhibited a positive relationship between [Ca2+]i and developed tension. The developed tension by PE was greater than that by high K+ at the same level of [Ca2+]i only in the aorta. A difference of regression slopes in the relationship between [Ca2+]i level and muscle tension under PE- and high K(+)-treatments in aorta was significant, but that in anococcygeus muscle was not. (4) An application of PE to anococcygeus muscle in Ca2+ free medium elicited a small transient contractile tension and increase in [Ca2+]i level, but that to aorta showed a large and transient increase in both the parameters. (5) Phorbol ester, DPB (1 microM), did not affect muscle tension or [Ca2+]i level in anococcygeus muscle, but DPB induced greater increases in aorta. (6) An application of PE (10 microM) with GTP produced a left shift in the pCa-tension curve in the beta-escin-permeabilized fiber of the anococcygeus muscle. In summary, it is suggested that the sustained contraction induced by PE in anococcygeus muscle is involved with the increases in [Ca2+]i which is due to Ca2+ influx mediated by alpha 1 receptor, but scarcely to Ca2+ release from the intracellular storage, and that an increase in Ca2+ sensitivity to PE is found only in the permeabilized anococcygeus muscle. The Ca(2+)-independent contractile mechanism in PE response as seen in aorta is probably to be absent in anococcygeus muscle. Moreover, it seems that the effect of the drug acting protein kinase C on anococcygeus muscle is extremely lesser than that on aorta.

Effects of beraprost sodium, a new prostaglandin I2 analog, on parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina.

The purpose of this study was to investigate the effects of beraprost sodium, a stable prostacyclin analog, on the parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. Thirty-one patients with exertional angina who had significant organic coronary artery stenosis in at least one of the three major coronary arteries were selected. All patients underwent quantitative exercise thallium-201 emission computed tomography before and 1 month after 120 micrograms per day of beraprost sodium administration. Before exercise, blood samples were collected from 8:30 a.m. to 9:30 a.m. after the patients had been lying in bed undisturbed for at least 10 minutes. Plasma platelet factor 4 (PF4), fibrinopeptide A (FPA), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 activity (PAI-1) were measured. There were no significant differences in exercise parameters on both exercise tests. However, both the extent and severity scores of ischemia were significantly aggravated (p < 0.05 for both) during beraprost sodium administration. Plasma FPA levels decreased significantly during beraprost sodium administration (p < 0.01). Likewise, plasma PF4 levels decreased significantly during beraprost sodium administration (p < 0.05). As for plasma t-PA antigen levels, there was no significant difference before versus during beraprost sodium administration. Plasma PAI-1 activity levels decreased significantly during beraprost sodium administration (p < 0.05). The results indicate that beraprost sodium has strong antithrombogenic properties. However, its aggravation of myocardial ischemia may limit clinical usage.

Changes in IgA and metals in serum and urine of human volume hypertension.

In this study, disturbance of immune response as a pathogenic mechanism for human volume hypertension was investigated and compared to nephritis in its correlation with the metals such as zinc, iron and aluminum as environmental factors. Urinary gamma-GTP excretions in patients with nephritis or hypertension were higher than in healthy people, whereas the plasma renin activity in these patients were lower on the average than in healthy individuals. Hypertensive patients participating in this study were diagnosed as the volume hypertension type from our clinical and other results. The serum IgM and IgA levels in renal patients showed a tendency to be lower than in the healthy people used as control. Urinary IgA excretion in hypertensive patients was increased in association with increasing excretions of aluminum and/or iron into urine. The values of regression coefficients in the urine samples for aluminum and iron vs. IgA, respectively, were very high at r = 0.900 (n = 9, p < 0.05) and 0.736 (n = 9, p < 0.05). These correlations were shown to be very useful indicators in diagnosing volume hypertension. Moreover, hypertensive patients in this study were demonstrated to have a high regression coefficient (r = -0.702, n = 7; p < 0.05) for calcium vs. renin in the serum. In the hypertension, augmentation of serum calcium significantly decreased plasma renin activity.

Determination of sagittal tongue shape from the positions of points on the tongue surface.

This paper describes a method for determining the shape of the midsagittal tongue contour from the positions of points on the tongue surface. The positions of the points and the tongue shape were measured simultaneously by using an alternating magnetic field device and an ultrasonic B-mode scanner for continuous speech utterances. A comparison between the magnetic and the ultrasonic data revealed that the average measurement difference between the two types of data was 1.16 mm. The shape of the tongue contour was then represented by multivariable linear regression of the magnetically determined positions. The results of the regression analysis showed that the tongue contour was estimated, from four positions on the tongue, with an average estimation error of 1.24 mm. This estimation error could be reduced to 0.84 mm when there was no measurement error between the magnetic and the ultrasonic data, and it was further reduced to 0.43 mm when the receiver coils of the magnetic device were positioned optimally on the tongue. It was also shown that the number of data frames for calculating the regression coefficients could be reduced, while maintaining the estimation accuracy, by appropriately selecting data frames. Finally, the tongue shape was estimated successfully for several phonemes from the magnetically determined positions, thus demonstrating the usefulness of this method for observing the articulatory configuration of the tongue.

Assessment of quantitative exercise thallium-201 emission computed tomography in patients with vasospastic angina--value of washout rate analysis.

This study was performed to assess the value of washout rate analysis of quantitative exercise thallium-201 emission computed tomography in vasospastic angina patients without significant coronary stenosis. Quantitative analysis of both thallium-201 perfusion and washout rate before and after drug treatment was performed in 48 patients with vasospastic angina and no significant coronary artery stenosis. All of the patients attained more than 90% of their age-predicted heart rate during each exercise test. Before drug treatment, 26 patients exhibited exercise-induced ischemia (perfusion defects on stress polar map), 17 did not exhibit exercise-induced ischemia (normal stress and washout rate polar maps), and the remaining 5 patients showed no perfusion defects, but did show extensive abnormal washout rates. On coronary angiography, multivessel coronary spasm was documented in 12 of the 26 patients with exercise-induced ischemia, in 7 of the 17 patients without exercise-induced ischemia and in 4 patients with an extensive abnormal washout rate and a normal stress polar map. In the 17 patients without exercise-induced ischemia, the mean washout rate was significantly decreased (p < 0.05) in association with a significant decrease in the double product (p < 0.05) after drug treatment. Of the 26 patients with exercise-induced ischemia, 18 (group 1) showed an increase in the mean washout rate with improved perfusion defect after drug treatment. The remaining 8 patients (group 2) showed a decrease in the mean washout rate with improved perfusion defect after drug treatment, which increased significantly on repeat exercise test performed after additional increased doses of antianginal drugs were administered (p < 0.01). The number of patients with multivessel coronary spasm was significantly high in group 2 (p < 0.01). Thirteen patients showed an extensive abnormal washout rate before drug treatment, including 8 patients with exercise-induced ischemia and 5 patients with no perfusion defects, who showed an increased mean washout rate after drug treatment (p < 0.05). These findings indicate that washout rate analysis aids in the diagnosis in vasospastic angina patients with exercise-induced ischemia. Some patients with exercise-induced ischemia can not be detected by thallium-201 perfusion analysis alone, especially those with multivessel coronary spasm and when this procedure is performed after drug treatment. In addition, a high frequency of abnormal washout rate in vasospastic angina may result not only from exercise-induced ischemia due to main epicardial coronary artery spasm, but also from microspasm, or impairment of microcirculation or myocyte.

A clinical feature of myocardial stunning associated with acute myocardial infarction.

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient's coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but sever ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.

[Ten-year results of argon laser trabeculoplasty].

One hundred and forty-seven eyes of 107 primary open angle glaucoma (POAG) patients and 39 eyes of 31 capsular glaucoma patients who were followed up for a minimum of 5 years after argon laser trabeculoplasty were reviewed. The mean preoperative intraocular pressure (IOP) was 23.6 mmHg. The follow-up periods ranged from 5 to 13 years with an average of 8.8 years. Using a life-table method, the probability of success was calculated, as defined by IOP at 21 mmHg or lower with same or less preoperative medical regimen, no deterioration of visual field defect and no requirement of filtering surgery. The success rate at 5 postoperative years was 40.3% for the POAG and 65.7% for the capsular glaucoma, and at 10 postoperative years it was 26. 8% for POAG and 26.9% for capsular glaucoma. An analysis using Cox proportional hazard model showed that preoperative lower IOP, male sex and higher age were the significant determinants for success.

Penetration of cefpirome into sputum in chronic respiratory infections: comparison of administration of 0.5 g and 1.0 g in the same patient.

This study evaluated the sputum penetration of cefpirome following slow intravenous infusion of 0.5 and 1.0 g using a comparative cross-over design to reduce variability. Five patients with chronic respiratory tract infections were randomized to receive either 0.5 g followed by 1.0 g, or by 1.0 g followed by 0.5 g cefpirome, by slow intravenous infusion over 1 h, with a 24-h wash-out period between each treatment. With the exception of one patient, sputum concentration correlated well with plasma concentration. Higher sputum levels of cefpirome were achieved following the higher dose.