儿童癌症试验性疗法是否优于标准疗法：儿童肿瘤研究组的多项随机临床对照试验的观察研究

目的:比较儿童期癌症标准疗法与Ⅲ期随机化临床试验阶段所验证的新疗法,研究新疗法优于或劣于标准疗法的概率;此类临床试验中,纳入患者的民族因素可能对试验结果造成不确定性影响,所以,本文还研究新疗法的成功和失败模式是否与前述不确定性影响之间存在一致性。试验设计:临床观     

Aerobic power of competitive paraplegic road racers.

The purpose of this study was to determine peak aerobic power and associated physiological responses in highly competitive spinal cord injured (SCI) paraplegic road racers. Seven (6 male and one female) active paraplegic (lesions T4-T12) road racers and 9 healthy untrained able-bodied males performed continuous graded arm crank ergometer tests to exhaustion for determinations of peak power output (PO), oxygen uptake (VO2), pulmonary ventilation (VE), heart rate (HR), and respiratory exchange ratio (RER). Compared to able-bodied subjects, male paraplegic road racers elicited significantly (p less than or equal to .05) higher mean (+/- SD) peak levels of PO (141.6 +/- 8.8 vs 111.4 +/- 27.7 W), absolute VO2 (2.72 +/- .52 vs 2.22 +/- .381/min), and VO2 per unit of body weight (43.06 +/- 7.4 vs 30.33 +/- 4.3 ml/kg/min). Although peak HR (180.3 +/- 9.5 vs 173.2 +/- 8.5 bpm) and VE (92.8 +/- 17.2 vs 74.6 +/- 20.3 l/min) tended to be higher for male paraplegic road racers than able-bodied subjects, the differences were not statistically significant. The female paraplegic road racer achieved the highest peak levels of PO (119 W) and VO2 (1.99 l/min; 38.0 ml/kg/min) reported to date for wheelchair-dependent women. These data suggest that intense physical training via wheelchair propulsion can markedly enhance upper body cardiovascular fitness in SCI paraplegics. However, the correlational analysis between 10 km time and peak VO2 was nonsignificant (p greater than .05) indicating that factors other than peak upper body aerobic power may influence wheelchair road racing performance.     

A developmental role for ataxia-telangiectasia mutated in protecting the embryo from spontaneous and phenytoin-enhanced embryopathies in culture.

Ataxia-telangiectasia (A-T) is characterized by impaired recognition and repair of DNA damage and increased sensitivity to ionizing radiation (IR), cancer, and neurodegeneration. We previously showed pregnant knockout mice lacking the A-T gene product ataxia-telangiectasia mutated (Atm) are highly susceptible to the embryopathic effects of IR, which damages DNA, possibly via generation of reactive oxygen species (ROS). Here we show that Atm more broadly protects against both spontaneous and phenytoin-enhanced embryopathies. In the absence of drug exposure, cultured embryos from pregnant Atm knockout mice showed more embryopathies than wild-type littermates, with a gene dose-dependent decrease in susceptibility from -/- to +/- to +/+ embryos (p < 0.05). A similar but significantly enhanced gene dose-dependent pattern of embryopathic susceptibility was evident in Atm knockout embryos exposed to the ROS-initiating teratogen phenytoin (p < 0.05). These results provide the first evidence that Atm has a broad developmental importance beyond IR embryopathies, possibly by protecting the embryo from constitutive and xenobiotic-enhanced oxidative stress, with even heterozygotes showing increased risk. This developmental role of Atm further implicates DNA damage in ROS-mediated teratogenesis and DNA damage response and repair as risk factors for individual susceptibility.     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. I. Taxonomy, production, isolation and biological activity.

A screen for antibiotics with activity against tetracycline-resistant microorganisms has led to the isolation of Dactylosporangium sp. (ATCC 53693), a producer of several novel tetracycline derivatives. The major fermentation products, dactylocyclines A and B, were purified and MIC values determined against tetracycline-resistant and tetracycline-sensitive Gram-positive bacteria. The dactylocyclines represent the first naturally occurring tetracycline C2 amides which lack cross resistance with tetracycline.     

High resolution computed tomography as a predictor of lung histology in systemic sclerosis

Background The relative proportions of fibrosis and inflammation seen by open lung biopsy examination is a predictor of disease outcome in fibrosing alveolitis. This study was designed to assess the ability of high resolution computed tomography to predict the histological appearance of open lung biopsy specimens from patients with systemic sclerosis.