信号核素134Cs诱发体细胞和生殖细胞畸变效应比较研究

对１３４Ｃｓ诱发体细胞和生殖细胞的畸变效应进行了比较研究。方法观察内污染不同放射性活度１３４Ｃｓ时诱发同体骨髓细胞和精原细胞染色体畸变的量效关系，以及同一放射性活度１３４Ｃｓ作用不同时间诱发上述两种细胞的染色体畸变产额。结果研究发现，１３４Ｃｓ内照射诱发的骨髓细胞染色体畸变产额显著高于精原细胞，而其诱发的染色体畸变类型均以染色单体型畸变为主。结论由不同放射性活度１３４Ｃｓ所诱发的染色体畸变产额而言，骨髓细胞要比精原细胞高出１．５～５倍。     

Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant

BACKGROUND: This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP. METHODS: In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 microg/d, 400 microg/d, or 800 microg/d of HFA-BDP or 100 microg/d, 400 microg/d, or 800 microg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment. RESULTS: Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV(1) percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV(1) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1) percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma). CONCLUSIONS: Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP.     

Evaluation of a new fletcher applicator using cesium-137

The improved Fletcher Applicator¹ is a recent modification of the afterloading Fletcher system. Its aluminum construction reduces the weight by 50 % and is more comfortable for the patient. Removable caps contain medially placed tungsten screens that shield tissues anteriorly and posteriorly. When the caps are removed, the colpostats can be used as Delclos mini-ovoids. A method for evaluating the dosimetry of brachytherapy applicators in a water phantom was devised so this applicator could be studied and compared with other gynecologic applicators. The results show that the transmission ratios—the fraction of radiation transmitted through the tungsten shields—differ from those of the preloaded Fletcher colpostat, but are similar to the transmission ratios of the Fletcher-Suit applicator. There is a 10 % to 25 % reduction in the radiation dose to the region of the bladder trigone and anterior rectum with the shield containing cap in place. This percent reduction in dose is in agreement with other Fletcher applicators. Misalignment of the source basket within the colpostat, and motion of the source in the carrier cause variations in the dose rate at specific distances from the colpostat.     

Microbial degradation of 2,4-dichlorophenoxyacetic acid: Insight into the enzymes and catabolic genes involved,their regulation and biotechnological implications

Abstract

A considerable progress has been made to understand the mechanisms of biodegradation of 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D biodegradation pathway has been elucidated in many microorganisms including Cupriavidus necator JMP134 (previously known as Wautersia eutropha, Ralstonia eutropha and Alcaligenes eutrophus) and Pseudomonas strains. It generally involves the side chain removal of 2,4-D by α-ketoglutarate-dependent 2,4-D dioxygenase (tfdA) to form 2,4-dichlorophenol (2,4-DCP); hydroxylation of 2,4-DCP by 2,4-DCP hydroxylase (tfdB) to form dichlorocatechol; ortho or meta cleavage of dichlorocatechol by chlorocatechol 1,2-dioxygenase (tfdC) to form 2,4-dichloro-cis,cis-muconate; conversion of 2,4-dichloro-cis,cis-muconate to 2-chlorodienelactone by chloromuconate cycloisomerase (tfdD); conversion of 2-chlorodienelactone to 2-chloromaleylacetate by chlorodienelactone hydrolase (tfdE) and, finally, conversion of 2-chloromaleylacetate to 3-oxoadepate via maleylacetate by chloromaleylacetate reductase and maleylacetate reductase (tfdF), respectively, which is funnelled to the tricarboxylic acid cycle. The latest review on microbial breakdown of 2,4-D, other halogenated aromatic pesticides, and related compounds was compiled by Haggblom, however, a considerable progress has been made in this area of research since then. Thus, this review focuses on the recent advancement on 2,4-D biodegradation, the enzymes, and genes involved and their biotechlogical implications.     

A method for large-scale, high-yield isolation of canine pancreatic islets of Langerhans

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas (approximately 3,500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections fo streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method is described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal.     

Symptomatic, electrocardiographic, metabolic, and hemodynamic alterations during pacing-induced myocardial ischemia

Atrial pacing has been used to assess the physiologic impact of coronary artery disease (CAD). Several variables have served as markers of pacing-induced myocardial ischemia, but their specificities and sensitivities are unknown. Accordingly, in 28 patients, incremental atrial pacing was performed. Of the 28, 10 had no CAD. The left ventricular ejection fraction (LVEF) (by gated equilibrium blood pool scintigraphy) increased in this group (0.60 ± 0.11 [mean ± standard deviation] before pacing to 0.67 ± 0.13 at peak-pacing, p = 0.002). In no patient did left ventricular end-diastolic pressure increase by > 5 mm Hg. No patient had lactate production, and 2 (20%) had electrocardiographic S-T segment depression ≥0.1 mV. Four (40%) had chest pain with atrial pacing. In the remaining 18 patients with CAD, atrial pacing caused a decrease in LVEF ≥0.05 (0.46 ± 0.10 to 0.33 ± 0.09, p < 0.001) and new segmental wall motion abnormalities in all, indicating pacing-induced myocardial ischemia. Only 8 (44%) had an increase in left ventricular end-diastolic pressure of > 5 mm Hg, and only 9 (50%) had lactate production. Ten (56%) had ischemic electrocardiographic changes, and 12 (67%) had chest pain. Thus, the electrocardiographic, metabolic, and hemodynamic alterations that may accompany pacing-induced ischemia are specific but relatively insensitive markers of ischemia. In contrast, chest pain during atrial pacing is a nonspecific occurrence, appearing with similar frequency in normal subjects and patients with CAD and pacing-induced ischemia.     

Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

The digoxin-quinidine interaction was studied in nine healthy human subjects aged 26 to 31 years. A single oral dose (400 mg) of quinidine sulfate administered to subjects taking digoxin resulted in a mean (± standard error of the mean) increase within 1 to 6 hours in the serum digoxin concentration of 0.12 ± 0.01 ng/ml (p <0.0001), an increase of 21 percent. Continued quinidine administration for 24 hours resulted in a 59 percent increase in the mean serum digoxin concentration from 0.68 ± 0.04 to 1.04 ± 0.06 ng/ml (alpha = 0.05). At the same time, however, systolic time intervals demonstrated a lengthening of the mean left ventricular ejection time index from 406 ± 4 to 419 ± 2 ms (alpha = 0.05) and the mean Q?S₂ Index from 524 ± 6 to 532 ± 7 ms (difference not significant [NS]). When compared with the shortening of these intervals predicted from the digoxin dose-response curve if digoxin were the only variable, the lengthening actually observed for both intervals was highly significant. The negative inotropic effect of quinidine administration alone was assessed with systolic time intervals in four subjects. The left ventricular ejection time index lengthened from 419 ± 3 to 425 ± 6 ms (NS) and the Q?S₂ index from 541 ± 6 to 550 ± 7 ms (NS). Therefore, the lengthening of these intervals in subjects taking digitalis after the addition of quinidine represents more than just the negative inotropic effect of quinidine, and occurs despite the increase in serum digoxin concentration.The results of this study support the view that quinidine displaces digoxin from tissue-binding sites as a major mechanism of the interaction. Furthermore, it appears that quinidine may specifically displace digoxin from cardiac-binding sites. These results raise important questions concerning the recommendation to reduce the maintenance digoxin dose when concomitant quinidine therapy is initiated.     

Comparison of verapamil and nifedipine in the treatment of variant angina pectoris: Preliminary observations in 10 patients

To assess the relative efficacy of verapamil, nifedlpine and placebo in the therapy of patients with variant angina pectoris, 10 such patients (6 men and 4 women, average age 52 years) were treated for 2 month periods with verapamil (mean ± standard deviation 400 ± 80 mg/day in three to six equal doses; range 240 to 480 mg/day), nifediplne (82 ± 31 mg/day in four to six equal doses; range 40 to 160 mg/day) and placebo. Eight of the 10 patients were maintained throughout the study on a stable regimen of oral isosorbide dinitrate (137 ± 56 mg/day in four to six equal doses; range 40 to 200 mg/day). Before the study, all underwent cardiac catheterization: eight had no fixed coronary artery disease, one had single vessel and one had triple vessel disease. Two patients had been resuscitated from sudden cardiac death before the study. Each patient underwent calibrated two channel ambulatory electrocardiographic monitoring for 24 hours during each week of the study.

During each 2 month period, the following data were quantitated: (1) chest pains per week, (2) nitroglycerin tablets used per week, (3) required hospitalizations for clinical instability, (4) adverse effects, and (5) episodes of transient S-T segment deviation on ambulatory monitoring. The number of chest pains per week, the number of nttroglycerin tablets used per week and the number of transient S-T segment deviations on calibrated two channel ambulatory electrocardiographic monitoring were similar during treatment with verapamil and nifedipine and less than with placebo. Hospitalization for clinical instability was required in two patients taking placebo and in two taking nifedipine; no patient required hospitalization during treatment with verapamil. Verapamil caused mild constipation in two patients, sinus nodal pauses in one patient and palpitations in one; none of these effects forced a discontinuation or substantial reduction in dosage. In contrast, the dosage of nifedipine was reduced because of induced orthostatic hypotension in two patients, marked pedal edema in one patient and nausea, anorexia and nonorthostatic dizziness in three. Thus verapamil and nifedipine showed similar efficacy in the treatment of variant angina, although nifedipine was associated with more substantial adverse effects than either placebo or verapamil in this small number of patients.     

Continuous electrocardiographic monitoring in patients with unstable angina pectoris: Identification of high-risk subgroup with severe coronary disease,variant angina,and/or impaired early prognosis

We assessed the value of two-channel Holter monitoring during the initial hours of hospitalization in patients with unstable angina pectoris (UAP) to identify those with severe coronary artery disease (CAD), variant angina, and/or poor prognosis over the next 3 months. Accordingly, 116 UAP patients had Holter monitoring for 27 ± 7 (mean ± SD) (range 12 to 50) hours following hospitalization. Of these, 24 evolved myocardial infarction (MI) during monitoring and 92 did not. Transient ST segment alterations occurred in 21 of the 92. Of these 21, 4 had variant angina, were treated with calcium antagonists, and did well. Each of the remaining 17 had severe fixed CAD (left main or three-vessel) (n = 12) and/or poor prognosis over the 3 months after discharge as manifested by death (n = 1), MI (n = 3), and/or severe angina (n = 3). In contrast, 71 patients did not demonstrate transient ST segment alterations: none had variant angina (p < 0.001), nine had left main or three-vessel CAD (p < 0.001), and 50 were alive and well 3 months after discharge (p < 0.001). Ventricular tachycardia (VT) was demonstrated by Holter monitor in 5 of the 92 patients: four had three-vessel CAD and the other had severe persistent angina. Thus in patients hospitalized with unstable angina, transient ST segment alterations and/or VT on Holter monitor are specific predictors of “high-risk” subgroup UAP patients with left main or three-vessel CAD, variant angina, and/or impaired 3-month prognosis.