Absolute and relative dose-surface and dose-volume histograms of the bladder: which one is the most representative for the actual treatment?

The purpose of this study was to quantify to what extent relative and absolute bladder dose-volume and dose-surface histograms of the planning CT scan were representative for the actual treatment. We used data of 17 patients, who each received 11 repeat CT scans and a planning CT scan. The repeat CT scans were matched on the planning CT scan by the bony anatomy. Clinical treatment plans were used to evaluate the impact of bladder filling changes on the four histogram types. The impact was quantified by calculating for this patient group the correlation coefficient between the planning histogram and the treatment histogram. We found that the absolute dose-surface histogram was the most representative one for the actual treatment.     

Efficient rescue of infectious bursal disease virus from cloned cDNA: evidence for involvement of the 3'-terminal sequence in genome replication

To study the mechanism of replication of infectious bursal disease virus (IBDV), and to determine factors on the IBDV RNA which are involved in viral replication, we used cloned full-length cDNA of both the A- and B-segments to generate infectious IBDV. Infectious IBDV was rescued from plasmids that contained full-length IBDV cDNA behind a T7 promoter, by transfecting these plasmids into cells which were infected with a recombinant Fowlpox virus that expressed T7 RNA polymerase. By using the cDNA transfection system we evaluated the effect of the length of the 3' terminus of the A-segment plus strand of IBDV. Although wild-type IBDV predominantly contains four cytosines at the 3' terminus, no difference in virus yield was found when virus was rescued from cDNAs containing three to six adjacent cytosines. When the 3' terminus was shorter than three cytosines the efficiency to generate infectious IBDV from cDNA was reduced, but IBDV could still be recovered reproducibly. The rescued viruses from cDNAs containing 3'-terminal deletions appeared to have a restored 3'-terminal sequence. The missing nucleotides are probably restored by using complementary bases of a stem-loop structure as template.     

A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers

The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender- and weight-matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender. The mean terminal elimination half-life (t1/2), however, was statistically significant between elderly and young subjects. Riluzole was well tolerated upon repeat dose administration. Headache was the most frequent adverse event reported, and there was no overt difference in the type, frequency, or severity of adverse events between elderly and young volunteers or between genders. In conclusion, these results indicate that no dosage adjustments of riluzole are required in the elderly.     

Ca2+ dependence of motilide-induced contractions in rabbit duodenal muscle strips in vitro

Summary Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called motilides. We have investigated the Ca²⁺-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydro-erythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin.Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca²⁺-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC₅₀ of 26 ± 5 nM for ME-34 (n = 7), and 27 ± 5 nM for EM-5231 (n = 16) and maximal responses of respectively 88 ± 4% and 80 ± 3%. Like motilin, both compounds induced an extra-contraction in depolarized tissues. The EM-523 response in 140 mM K⁺under isotonic conditions was 84 ± 3% (n = 5) at 10^–5 M, with an EC₅₀ that was shifted to 65 ± 18 nM. Similar figures were obtained for ME-34. When Ca²⁺ was added to Ca²⁺-depleted strips, half-maximal Ca²⁺ values (in mM) were 1.10 ± 0.11 (n = 9) for EM-523 and 1.13 ± 0.12 (n = 3) for ME-34, as compared with 1.12 ± 0.13 (n = 7) for motilin and 2.8 ± 1.1 (n = 9) for K⁺. Both ME-34 and EM-523 also induced a transient contraction in Ca⁺-free solutions under isometric conditions. The response to EM-523 (5 × 10^–6 M) was 49 ± 15% (n = 4) after 3 min. A maximal EM-523 -stimulation reduced a subsequent ACh response by 78 ± 7%, whereas EM-523 and ME-34 could not induce a contraction after ACh.We conclude that motilides depend upon external Ca²⁺ to a similar extent to motilin. Like motilin, they are also able to mobilize intracellular Ca Z + stores. Our results support the hypothesis that motilides act on motilin receptors. Send offprint requests to T. L. Peeters at the above address     

Cardiac adaptation to pregnancy in women with a history of preeclampsia and a subnormal plasma volume

In former preeclamptics, a subnormal plasma volume (LPV) predisposes to hemodynamic maladaptation to pregnancy. Here, we assessed the initial cardiovascular response to pregnancy in LPV (n = 20), in former preeclamptics with normal plasma volume (NPV) (n = 35) and in parous controls (CONTR) (n = 9) by echocardiography, blood pressure and heart rate (HR), before pregnancy, and by 5 and 7 weeks amenorrhea. Data analysis was by nonparametric tests. LPV differed from NPV and CONTR, by a consistently lower E/A ratio (ratio of peak mitral flow velocity in early diastole [E] and that during atrial contraction [A]) and an early-pregnancy rise in left atrial diameter (LAD). Both NPV and LPV differed from CONTR by an early-pregnancy rise in HR. The consistently lower E/A ratio together with the early-pregnancy LAD rise in LPV indicate diastolic dysfunction. The early-pregnancy rise in HR suggests sympathetic dominance in the autonomic control of the circulation.     

Orthostatic stress response during the menstrual cycle is unaltered in formerly preeclamptic women with low plasma volume

Plasma volume (PV) varies with the menstrual cycle not only in healthy parous controls (CON) but also in formerly preeclamptic women with a subnormal PV (LPV). It is unknown whether formerly preeclamptic women with LPV are more susceptible to orthostatic stress than healthy controls. In this study, the authors compared autonomic responses to acute (standing from supine position) and gradual (menstrual cycle) orthostatic stress between LPV and CON. In 11 LPV (PV相似文献   

海南省HIV-1基因亚型分析

目的 分析海南省人类免疫缺陷病毒-1(HIV-1)基因亚型,监测HIV毒株的流行状况.方法 从88份HIV-1抗体阳性的血浆中提取RNA,逆转录后采用PCR法扩增HIV-1基因序列中的env及pol基因,对扩增产物进行核苷酸序列测定,经比对分析而确定基因亚型.构建最大似然(ML)进化树,分析感染者间的传播链.结果 88份样品中,有83份样品被扩增出HIV-1的env及pol基因片段;共发现6种HIV-1亚型和重组型,其中CRF01-AE亚型70份,B'亚型8份,C亚型2份,B亚型和CRF08-BC、CRF01-AE/B'重组亚型各1份.在ML进化树上83份样品分成4个传播群(66/83)和非传播群(17/83),其中传播群1最庞大(59/83).结论 海南省HIV/AIDS的HIV-1基因亚型至少有6种,其中CRF01-AE为主要亚型,占84.33%(70/83),主要分布在静脉吸毒者及其性伴侣之间,形成了一个庞大的传播群.其次为B'亚型(9.6%).另外的4种亚型(6%)仅见单个病例.提示海南省静脉吸毒为主要的感染途径(67.5%);经性接触传播的亚型种类复杂多样,包括本次检出的全部亚型和重组株.     

Assessment of hepatic perfusion parameters with dynamic MRI.

Quantification of hepatic perfusion parameters greatly contributes to the assessment of liver function. The purpose of this study was to describe and validate the use of dynamic MRI for the noninvasive assessment of hepatic perfusion parameters. The signal from a fast T(1)-weighted spoiled gradient-echo sequence preceded by a nonslice-selective 90 degrees pulse and a spoiler gradient was calibrated in vitro with tubes filled with various gadolinium concentrations. Dynamic images of the liver were obtained after intravenous bolus administration of 0.05 mmol/kg of Gd-DOTA in rabbits with normal liver function. Hepatic, aortic, and portal venous signal intensities were converted to Gd-DOTA concentrations according to the in vitro calibration curve and fitted with a dual-input one-compartmental model. With MRI, hepatic blood flow was 100 +/- 35 mL min(-1) 100 mL(-1), the arterial fraction 24 +/- 11%, the distribution volume 13.0 +/- 3.7%, and the mean transit time 8.9 +/- 4.1 sec. A linear relationship was observed between perfusion values obtained with MRI and with radiolabeled microspheres (r = 0.93 for hepatic blood flow [P < 0.001], r = 0.79 for arterial blood flow [P = 0.01], and r = 0.91 for portal blood flow [P < 0.001]). Our results indicate that hepatic perfusion parameters can be assessed with dynamic MRI and compartmental modeling.