The NS gene--a possible determinant of apathogenicity of a cold-adapted donor of attenuation A /Leningrad/134/47/57 and its reassortants

Phenotypical properties of single-gene reassortants of attenuated cold-adapted strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory animals were studied. Only the group of reassortants inheriting NS gene from cold-adapted virus was fully attenuated for various animals species, similarly as reassortants with 6/2 genomic formula containing all the 6 internal protein genes from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature-sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis of reassortants with 6/2 genomic formula was noticeably reduced at this temperature. Hence, a similar level of attenuation of both reassortant groups appears to be due to various molecular mechanisms. Possible role of NS2 gene mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is discussed.     

Retrograde coronary venous infusion of ethanol for ablation of canine ventricular myocardium

INTRODUCTION: Permanent cure of reentrant ventricular tachycardia (VT) associated with coronary artery disease is difficult to achieve. Retrograde coronary venous infusion of ethanol for ablation of ventricular myocardium associated with reentrant tachyarrhythmias has several potential advantages, including use of physiologic mapping techniques and production of deeper, wider necrotic zones. METHODS AND RESULTS: Nine anesthetized dogs had baseline hemodynamic measurement, left ventriculography, coronary arteriography, occlusive coronary venography, and programmed electrical stimulation of the right ventricular apex and outflow tract. A balloon-tipped infusion catheter was advanced into a distal coronary venous branch, the balloon slowly inflated, and pure ethanol infused at volumes of 1.5, 3, or 5 cc. Hemodynamic measurements, angiography, ventriculography, and programmed electrical stimulation were repeated immediately and 1 week following ablation. Formalin-perfused hearts were serially sectioned and lesion volumes determined. Histologic examination of ablation beds then was performed. No significant difference was found in any hemodynamic measurement before or after ablation. Coronary arteriograms and left ventriculograms were unchanged after ablation. Nonsustained VT occurred in eight dogs during ethanol infusion; however, VT was not inducible in any dog before or after ablation. Infusion volumes of 3 cc or more were required to produce transmural lesions. CONCLUSION: Retrograde coronary venous infusions of ethanol using a balloon-tipped infusion catheter were effective in ablating ventricular myocardium. Retrograde chemical ablation did not itself result in inducible VT or adversely affect hemodynamic measurements or coronary arteries. Transmural myocardial necrosis, necessary in the ablation of VT associated with coronary artery disease, can be produced by higher infusion volumes.     

Ion-pair high-performance liquid chromatography for determining disaccharide composition in heparin and heparan sulphate

Rats deficient in vitamin A express low levels of P4502C7 mRNA in the liver. Administration of all-trans retinoic acid (at-RA) or growth hormone (GH) to deficient animals only partially restored the expression whereas the combined treatment returned the P4502C7 mRNA levels to that observed in normal rats. That a retinoid is the predominant inducer of P4502C7 at the cellular level is evident from studies performed with primary hepatocytes, but it became clear that GH is a prerequisite for the vitamin A effect in vivo. The at-RA induction of P4502C7 mRNA in primary rat hepatocytes was inhibited by ketoconazole, an inhibitor of P450 activity, and by cycloheximide, blocking ongoing protein synthesis. In contrast, the at-RA induction of RAR-beta2 mRNA was not affected by any of these compounds. This could indicate previously not recognized mechanisms of at-RA action. Interestingly, at-4-oxo-RA, an at-RA metabolite formed by a P450 catalyzed reaction, also induced P4502C7 mRNA. Induction of P4502C7 mRNA by the retinoic acid receptor (RAR) selective agonist TTNPB indicated that this pathway is preferred over the retinoid X receptor (RXR) pathway. In addition, analysis of RA metabolites in liver cell extracts revealed the formation of several as yet unidentified metabolites. The formation of some of these metabolites was inhibited by ketoconazole and they could therefore constitute potential inducers of CYP2C7. We suggest that metabolism of at-RA, possibly by a P450 enzyme, is an important step in the at-RA induction of P4502C7.     

Random and fuzzy sets in coarse data analysis

The theoretical aspects of statistical inference with imprecise data, with focus on random sets, are considered. On the setting of coarse data analysis imprecision and randomness in observed data are exhibited, and the relationship between probability and other types of uncertainty, such as belief functions and possibility measures, is analyzed. Coarsening schemes are viewed as models for perception-based information gathering processes in which random fuzzy sets appear naturally. As an implication, fuzzy statistics is statistics with fuzzy data. That is, fuzzy sets are a new type of data and as such, complementary to statistical analysis in the sense that they enlarge the domain of applications of statistical science.     

The diagnosis and treatment of bladder cancer metastases

Central hemodynamics was studied by thermodilution in 16 patients with acquired mitral defect during surgery under conditions of hypothermia without perfusion. Cooling and surgical correction were carried out under superficial ether anesthesia with morphine and droperidol. A 28% decrease of the minute circulation volume is observed as early as under general anesthesia and at the very beginning of cooling (10.8% more); this decrease is caused by rarer heart contractions and increase of the total peripheral vascular resistance as a result of body response to cool exposure. An almost 10 degrees C drop of body temperature (to 27.2 +/- 0.2 degrees C) involves a just 13% decrease of the cardiac index in comparison with the value at the beginning of cooling. Injection of droperidol before cooling blocks the increase of the total peripheral resistance in a dose-dependent mode (about 0.13 mg/kg of droperidol is needed for sufficiently complete prevention of the increase of total peripheral resistance), and thus maintains the stroke and cardiac indexes at a sufficiently high level. Morphine (in doses of up to 2.3 mg/kg) did not bring about such an effect.     

Sex-based and hormonal contraception effects on the metabolism of nicotine among adolescent tobacco-dependent smokers.

Variations in nicotine metabolism influence smoking patterns. Differences between sexes or related to sex hormones may affect nicotine metabolism. Because smoking initiation starts during adolescence, observations gathered from adolescent smokers might broaden our understanding of such sex-based differences. We tested the hypothesis that nicotine metabolism--as indexed primarily by the ratio of trans-3'-hydroxycotinine (3HC) to cotinine--is more rapid among adolescent girl smokers compared with boys and that regular use of hormonal contraceptives influences nicotine and cotinine metabolism. We also hypothesized that more rapid nicotine metabolism is associated with higher nicotine dependence as indexed by smoking frequency and morning urgency. Plasma samples of nicotine, cotinine, and 3HC concentrations were obtained from 120 adolescents (36 boys). Plasma nicotine and cotinine concentrations were similar in boys and girls. Median plasma 3HC concentrations were 44.45 ng/ml for girls versus 35.74 ng/ml for boys (p = .025), and median plasma 3HC-cotinine ratios were significantly higher in girls than in boys (0.317 vs. 0.253, p = .025). After stratifying girls into two groups based on use versus nonuse of hormonal contraception, plasma 3HC-cotinine ratios in girls using hormonal contraception (0.47) were substantially higher (p<.0001) than in boys (0.25) and were significantly higher than in girls not using hormonal contraception (0.28). Controlling for cigarettes smoked per day, ethnicity, and age did not modify these results. Although plasma nicotine, cotinine, or 3HC concentrations were significantly lower in less dependent adolescent smokers, nicotine and cotinine metabolite ratios were similar. This study showed that hormonal contraception in adolescent girls may accelerate cotinine metabolism, an effect likely related to induction of cytochrome P450 2A6 and independent of ethnicity and cigarette consumption. Prospective controlled studies are needed to further evaluate the role of hormonal contraception in patterns of adolescent smoking and nicotine metabolism.     

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.