血管紧张素原基因5’端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

目的:分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性。方法:实验于2005-08/2006-01在北京华大实验室完成。选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族。采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异。结果:①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和临床化验检查指标有较好的匹配(P均>0.05)。②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,χ2=0.395,P=0.529)。A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,χ2=0.015,P=0.904)。③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,χ2=1.924,P=0.165)。A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,χ2=1.728,P=0.189)。④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(χ2=2.395,P=0.122,OR=7.52,95%CI0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,χ2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI1.087～7.271)。结论:血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用。     

High‐frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency

Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.     

Conceptual issues specifically related to health-related quality of life in critically ill patients

During recent years increasing attention has been given to the quality of survival in critical care. Health-related quality of life (HRQOL) is an important issue both for patients and their families. Furthermore, admission to the intensive care unit can have adverse psychological effects in critically ill patients. Recent studies conducted in critically ill patients have measured HRQOL. However, usually absent from such reports are evaluations of conceptual issues, addressing factors such as why HRQOL should be measured in critically ill patients, how to define and standardize domains of HRQOL, whether proxies can provide useful information about HRQOL in critically ill patients, whether response shift occurs in critically ill patients, and whether post-traumatic stress disorder (PTSD) occurs in critically ill patients. Some studies reported moderate agreement between patients and their proxies, although lower levels of agreement may be reported for psychosocial or physical functioning. Response shift (adaptation and change in perception) appears to be an important phenomenon and likely to be present, but it is seldom measured when estimating HRQOL in critically ill patients. Furthermore, vigilance for symptoms of PTSD and early interventions to prevent PTSD are needed.     

Pathway analysis of gene signatures predicting metastasis of node-negative primary breast cancer

Background  

Published prognostic gene signatures in breast cancer have few genes in common. Here we provide a rationale for this observation by studying the prognostic power and the underlying biological pathways of different gene signatures.     

Effects of a night-float system on resident activities and parent satisfaction.

Night-float systems have recently been proposed as a way to reduce resident stress resulting from irregular sleep patterns. We prospectively evaluated the effects of a night-float system in which designated residents relieved on-call senior residents and interns of routine admissions of patients in medically stable condition during the late-night period (11 PM to 7 AM). Senior residents (3.7 vs 2.4 hours) and interns (3.7 vs 3.2 hours) reported sleeping more under the night-float system than under the traditional system. The night-float system did not affect residents' overall ratings of call nights. Educators who reviewed medical records agreed with residents' decisions about patients' appropriateness for admission using the night-float system in 95 (81%) of 117 cases. When educators disagreed with residents, the most common reasons were the patient's potential educational value or medical instability. The night-float system did not affect interns' ratings of the educational value of late-night admissions or parents' ratings of satisfaction with medical care. We conclude that the night-float system can increase resident sleep with little cost to parent satisfaction, but standards for selective use may be needed to avoid compromising patient care and resident education.     

Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years

OBJECTIVE: To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years. DESIGN: Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months. SUBJECTS: 290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis. MAIN OUTCOME MEASURES: Age and sex standardised z scores for height, weight, and body mass index. RESULTS: 459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height. CONCLUSIONS: Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years.     

Effect of spectral distribution on isomerization of bilirubin in vivo

The purpose of our study was to compare the effects of narrow-spectrum blue light and broad-spectrum white light on the production of bilirubin photo-isomers in human infants with jaundice. Twelve preterm infants were studied under both white and blue light. Irradiance at 450 nm was controlled at 12 microW/cm2/nm for both light sources. Each light condition (white or blue) was administered for 12 hours. Bilirubin isomers (4Z,15E-bilirubin and lumirubin) were measured before therapy and after 12 hours of each sequential light condition. The percentage of 4Z,15E-bilirubin was greater under blue light than under white light (P less than 0.01) phototherapy. There was no significant difference in percentage lumirubin under white or blue light therapy. Our data indicate that blue light is more effective than white light in producing 4Z,15E-bilirubin in vivo. Our study demonstrates that when irradiance in the bilirubin absorbance spectrum is constant, the color of light (spectral distribution) will determine the relative concentrations of photo-isomers produced.     

Preclinical efficacy evaluations of XK-469: dose schedule,route and cross-resistance behavior in tumor bearing mice

XK-469 is advancing to Phase I clinicaltrials. Preclinical studies were carriedout to assist in clinical applications.Dose-schedule route testing: Singledose IV treatment with XK-469 producedlethality (LD20 to LD 100) above 142 mg/kg.Optimum treatment required total dosages of350 to 600 mg/kg. Furthermore, highindividual IV dosages (100 to 142 mg/kg)were poorly tolerated, producingsubstantial weight loss (8 to 18% of bodyweight), poor appearance, and slow recovery(8 to 12 days). A 1-hour infusion ofdosages more than 140 mg/kg, or BIDinjections 6 hrs apart, did not reducelethality. However, lower individualdosages of 40 to 50 mg/kg/injection IV werewell tolerated and could be given daily toreach an optimum total dose with minimaltoxicities. Likewise, 75 mg/kg/injection IVcould be used every other day to reachoptimal treatment. The necropsy profiles ofdeaths from toxic dosages were essentiallyidentical regardless of schedule (deaths 4to 7 days post treatment). The profileswere: paralytic ileus or gastroparesis; GIepithelial damage; and marrow toxicity.Interestingly, the key lethal events wererapidly reversible and simple to overcomewith lower dosages given daily or everyother day. Based on these results, the highdose, Q21day schedule should be avoided inclinical applications. Instead, a splitdose regimen is recommended (e.g., daily,every other day, or twice weekly). XK-469was also well tolerated by the oral route,requiring 35% higher dosages PO to reachthe same efficacy and toxicity as producedIV. Cross-resistance studies: XK-469resistance was produced by optimumtreatments of IV implanted L1210 leukemiaover seven passage generations. Thisleukemia subline (L1210/XK469) had reducedsensitivity to VP-16 (with a 4.0 log killin IV implanted L1210/XK469 compared to an8.0 log kill against IV implanted L1210/0). It also had a reduction in the sensitivityto 5-FU (with a 2.0 log kill in theimplanted L1210/XK469 compared to a 4.0 logkill against IV implanted L1210/0). Otheragents were approximately as active againstthe resistant tumor, including: Ara-C,Gemzar, Cytoxan, BCNU, DTIC, and CisDDPT. No case of collateral sensitivity wasobserved; i.e., no agent was markedly moreactive against the resistant sublineL1210/XK-469 than against the parent tumorin mice.     

Sarcomatoid renal cell carcinoma: Rapid dissemination detected on FDG PET‐CT

We present the FDG PET‐CT findings in a patient with persistent pain 7 weeks after a nephrectomy and lymph node dissection for a sarcomatoid renal cell carcinoma. Although conventional imaging was unable to detect evidence of metastatic spread outside the para‐aortic nodes, a PET‐CT scan showed unexpected extensive dissemination. Currently, there are no reports in the literature of the PET‐CT findings in sarcomatoid renal cell carcinomas.