Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.

To assess quantitatively the risks of ophthalmic beta-blocking agents for cardiovascular and respiratory adverse reactions, we analyzed the binding kinetics of beta-blocking agents to the beta-1 and beta-2 adrenoceptors. The relationship between the occupancies for beta-1 and beta-2 adrenoceptors and the effects on the exercise pulse rate or the forced expiratory volume in one second (FEV1) after topical administration of carteolol, befunolol, timolol and betaxolol was analyzed using a ternary complex model. The beta-1 and beta-2 receptor occupancies after ophthalmic administration were calculated to be quite high as well as those after oral administration. The maximum occupancies for beta-1 and beta-2 receptors after ordinary ophthalmic administration were 52% and 88% for carteolol, 52% and 61% for befunolol, 62% and 82% for timolol, and 44% and 3% for betaxolol, respectively. Concave relationships were obtained between a decrease in exercise pulse rate and the beta-1 receptor occupancy and between a decrease in FEV1 and beta-2 receptor occupancy, respectively. Nasolacrimal occlusion was estimated to decrease the exercise pulse rate and FEV1 by 65% and 50%, respectively. The beta-1 and beta-2 adrenoceptor occupancies were proved to be the most appropriate indicators for cardiac and pulmonary adverse reactions evoked by ophthalmic beta-blocking agents.

[Detection size dependence of field factor for narrow beam].

An absorbed dose in the narrow beam is calculated based on the depth dose distribution and a field factor. The field factor has to be measured with especially high accuracy because it is highly variable. The field factor was calculated when detection size was changed, by using Monte Carlo simulation, which had no energy dependency or geometrical error. Then the relation between field factor and detection size in the narrow beam was investigated. An absorbed dose in peak depth and reference depth according to detection size was calculated for each field size. Detection size dependency was recognized in the case of measuring a field factor, because the absorbed dose tended to decrease as detection size increased. The absorbed dose in the narrow beam has to be calculated within a change of +/- 2%. The change in peak depth according to detection size was eliminated, and then the relation between an absorbed dose at the ideal detection size of 0 mm phi by extrapolation and detection size which has a deference of 2% from it, were acquired. In addition, the maximum usable detection size was estimated in the case of measuring the field factor.

[Effective management and its counter plan in clinical laboratories].

The effective management for clinical laboratories at Kitasato University Hospital in these seven years was reported. To improve the economical efficiency, I pointed out that it is important to improve the efficiency of the laboratory work and to reorganize the clinical laboratory. In addition, we may have to take advantage of contract tests in consideration of profit-and-loss. On the other hand, it is desirable among the clinicians to improve emergency tests, to support their research, to consult on the test results and to ask for any additional interpretations of the obtained data. A system that can satisfy their needs should be established.

Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and western-blot assessment with special reference to their cellular sources in periodontal diseases.

The characterization and regulation of matrix metalloproteinases (MMPs) have been studied to determine their role(s) in periodontal tissue destruction. Progress in elucidating the roles of MMPs in periodontal tissue destruction has led to a new concept involving the chemotherapeutic inhibition on MMPs, a therapeutic strategy which less than a decade ago was considered "a difficult and perhaps impossible task." Tetracyclines/doxycycline (DOXY) and their chemically modified nonantimicrobial derivatives (CMTs) are known to inhibit the matrix metalloproteinases, especially preferring human neutrophil collagenase (MMP-8), and prevent the oxidative activation of procollagenases. We characterized by Western blotting the molecular forms and cellular sources of gingival tissue, dental plaque, gingival crevicular fluid (GCF), and salivary MMPs associated with periodontitis. Also the molecular forms of tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) in periodontitis were studied by Western blot. Neutrophil (PMN)-derived MMPs were found to predominate in periodontitis, and phospholipase C present in increased amounts in periodontitis sites was found to be a potential inducer of PMN degranulation. We further studied the effects of DOXY on molecular forms of different latent and active MMPs purified from different cellular sources (PMNs, fibroblasts, keratinocytes) and present in vivo in oral exudates (gingival extracts, GCF, and saliva). DOXY inhibition of activated (oxidatively or proteolytically) MMPs were not associated with MMP fragmentation. Michaelis-Menten plots of initial rates of degradation of soluble type I collagen revealed an apparent Km value of 0.3-0.6 microM for MMP-8, and 75 microM DOXY inhibited MMP-8 in a manner which did not result in changes in apparent Km value but did prevent the initial degradation reaching Vmax providing evidence for noncompetitive inhibition. Treatment of patients with long-term DOXY medication results in decreased MMP-8 activities/levels in gingival tissue, crevicular fluid, and saliva, but not fragmentation of MMP-8 in vivo. These data further support and extend the key role of PMN-MMPs in periodontitis, and the activities of these PMN MMPs can be inhibited directly by therapeutic levels of DOXY.

[Quantitative assessment of improvement in perfusion after coronary bypass grafting: assessed by thallium-201 bull's eye subtraction polar map method].

To assess redistribution (RD) and improvement in regional perfusion after coronary bypass grafting (CABG) on thallium-201 SPECT images quantitatively, the Bull's eye subtraction polar (BS) map was created. BS map was created after subtraction of a normalized bull's eye polar map from another normalized polar map. The quantitative assessment on this map was compared to the visual qualitative analysis in 23 patients (115 segments) who received CABG. All of the improved segments after CABG showed > or = 15% on the BS map. On the other hand, 60% of the non improved segments showed < 10% on the BS map. Furthermore, 67% of the RD segments showing > or = 15% on the BS map before CABG improved in perfusion by > or = 15% on the BS map after CABG. On the BS map, an excellent correlation was observed between the extent of redistribution before CABG and the extent of improvement after CABG. Thus, BS map permits quantitative assessment of improvement in perfusion on T1 SPECT imaging, and this technique seems to be valuable for predicting improvement in perfusion after CABG.

[Assessment of resting thallium-201 reinjection after stress-delayed Tl imaging (I): Comparison with 24-hour scan and regional wall motion].

Clinical value of resting reinjection of 1 mCi (37 MBq) of Tl after stress-delayed scan was assessed in comparison with 24 hr delayed scan and regional wall motion (RWM) in 37 patients with coronary artery disease. Of 101 segments with initial perfusion abnormality, concordant findings were observed after Tl reinjection in 67 segments (66%). But redistribution (RD) after Tl reinjection was observed in 19 of the 52 persistent defect (PD) segments (37%), and complete RD was observed 15 of the 43 segments (35%) where 3 hr scan showed incomplete RD. On the other hand, concordant findings were observed on 24 hr delayed scan in 11 of the 20 segments with perfusion abnormality (55%). RD on 24 hr delayed scan was observed in 5 of the 13 PD (38%), but it was not apparent in 3 of the 7 segments where 3 hr scan showed RD. Furthermore the segments which showed RD after Tl reinjection in PD segments tend to have less severe RWM abnormality than the sustained PD segments (RWM score: 1.65 +/- 1.17 vs. 2.29 +/- 1.05, p less than 0.05). These data indicate that Tl reinjection which permits assessment of RD with good quality images on the same day is considered as a valuable means for assessing myocardial viability.

[Assessment of myocardial viability by quantitative analysis of stress Tl-SPECT--comparison with FDG-PET].

Stress Tl-201 tomography (SPECT) is widely used for evaluating myocardial viability. To assess its value, redistribution (RD) on SPECT was compared with metabolic imaging using FDG. Thirty patients with coronary artery disease underwent stress-3 hour Tl-201 SPECT and PET using N-13 ammonia and FDG. RD was classified into 4 grading, including complete RD (CR), incomplete RD (IR), persistent defect (PD) and additional minimal RD (MR) defined as no definite RD on visual analysis but faint RD with Bull's eye quantitative analysis (QNT). All but one segment with CR or IR were viable regions (normal or ischemic regions) by PET. Of 74 segments without RD on visual analysis, 31 segments (42%) had RD by QNT (MR). All of them were viable regions by PET. Thus, QNT identified 31 segments (63%) of the metabolically viable segments which the visual Tl-201 analysis did not show RD and classified as myocardial scar. However, even such QNT cannot detect ischemic myocardium in 18 segments (42%) containing metabolic activity on PET. These data indicate that QNT of RD on Tl-201 SPECT is considered as a valuable means for assessing myocardial ischemia.

[Serial assessment of cardiac function during and after exercise by an ambulatory ventricular function monitor (VEST)].

Cardiac function was serially assessed during and after exercise by an ambulatory ventricular function monitor (VEST) in 31 patients who received coronary angiography. Based on the study of fluctuation during the baseline recording, greater than or equal to 6% change in ejection fraction (EF) was considered significant. The serial changes in EF during exercise was divided into 5 types, including continuous increase (type A), initial increase but return to the baseline (type B), no change (type C), initial increase but later decrease below the baseline (type D), and continuous decrease (type E). Among 8 normal subjects, their EF changes during exercise showed type A in 3, type B in 2, type C in 2, and type D in 1. Among 21 patients with coronary artery disease, the EF changes showed type A in 5, type B in 4, type C in 4, type D in 5 and type E in 3. Thus, there was a significant overlap in EF response between normal and coronary patients. However, every patient showing type A and B had single-vessel disease, and 63% of them had persistent thallium defect without redistribution. After the exercise, 29 patients showed rapid increase in EF. The time to the peak EF was significantly longer in coronary patients (1.88 +/- 1.24 min) than that in normal cases (0.88 +/- 0.55 min) (p less than 0.05) particularly in patients with multi-vessel disease (2.22 +/- 1.29 min). In addition, those showing type C, D or E tended to have a longer time to peak EF and more increase in EF after exercise than those showing type A or B. These data suggest that VEST is suitable for continuous measurement of cardiac function during and after exercise which provided valuable indices for assessment of severity of ischemia in coronary artery disease.