Weekly irinotecan in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure

Background: The cytotoxic treatment of patients suffering from advanced or metastatic cancer undergoing hemodialysis due to chronic renal failure still remains a problem, since for those patients pharmacokinetic and pharmacodynamic data on most cytotoxic agents are lacking. Case Report: We report a 45-year-old male who suffered from chronic renal failure and was diagnosed with stage-3 colorectal cancer (CRC) in February 2000. After surgical removal of the tumor an adjuvant chemotherapy of dose-reduced i.v. bolus 5-fluorouracil and folinic acid was begun (Mayo protocol). Due to excessive gastrointestinal toxicity, therapy was discontinued after the first cycle. In April 2000 liver metastases were diagnosed. The patient was then put on a weekly schedule of dose-reduced CPT-11 (50 mg/m(2), 80 mg total). No hematological or non-hematological toxicity grade 3/4 was observed. Due to excellent tolerability and lack of severe side effects the dose was increased up to 80 mg/m2 (140 mg total) weekly. A dose escalation to 100 mg/m(2) (180 mg total) resulted in severe diarrhea (grade 4). Within 2 months of treatment the patient achieved a lasting partial remission until April 2001 (12 months). A significant progression of hepatic metastases required an alternative treatment regimen beginning in July 2001 (HAI, hepatic artery infusion). Conclusion: This case report demonstrates the feasibility and efficacy of a weekly treatment with dose-reduced CPT-11 in a patient with metastatic CRC on hemodialysis due to chronic renal failure

The coevolution of toxin and antitoxin genes drives the dynamics of bacterial addiction complexes and intragenomic conflict

Bacterial genomes commonly contain ‘addiction’ gene complexes that code for both a toxin and a corresponding antitoxin. As long as both genes are expressed, cells carrying the complex can remain healthy. However, loss of the complex (including segregational loss in daughter cells) can entail death of the cell. We develop a theoretical model to explore a number of evolutionary puzzles posed by toxin–antitoxin (TA) population biology. We first extend earlier results demonstrating that TA complexes can spread on plasmids, as an adaptation to plasmid competition in spatially structured environments, and highlight the role of kin selection. We then considered the emergence of TA complexes on plasmids from previously unlinked toxin and antitoxin genes. We find that one of these traits must offer at least initially a direct advantage in some but not all environments encountered by the evolving plasmid population. Finally, our study predicts non-transitive ‘rock-paper-scissors’ dynamics to be a feature of intragenomic conflict mediated by TA complexes. Intragenomic conflict could be sufficient to select deleterious genes on chromosomes and helps to explain the previously perplexing observation that many TA genes are found on bacterial chromosomes

Detailed analysis of radiation data from the Gemini 4 and Gemini 7 proton-electron spectrometer experiments Final report, 13 Jun. 1967 - 30 Dec. 1968

Detailed analysis of radiation data from Gemini 4 and 7 proton-electron spectrometer experiment

Solar wind data from the MIT plasma experiments on Pioneer 6 and Pioneer 7

Hourly averages are presented of solar wind proton parameters obtained from experiments on the Pioneer 6 and Pioneer 7 spacecraft during the period December 16, 1965 to August 1971. The number of data points available on a given day depends upon the spacecraft-earth distance, the telemetry bit rate, and the ground tracking time allotted to each spacecraft. Thus, the data obtained earlier in the life of each spacecraft are more complete. The solar wind parameters are given in the form of plots and listings. Trajectory information is also given along with a detailed description of the analysis procedures used to extract plasma parameters from the measured data

Large-Scale Magnetic-Field Generation by Randomly Forced Shearing Waves

A rigorous theory for the generation of a large-scale magnetic field by random non-helically forced motions of a conducting fluid combined with a linear shear is presented in the analytically tractable limit of low Rm and weak shear. The dynamo is kinematic and due to fluctuations in the net (volume-averaged) electromotive force. This is a minimal proof-of-concept quasilinear calculation aiming to put the shear dynamo, a new effect recently found in numerical experiments, on a firm theoretical footing. Numerically observed scalings of the wavenumber and growth rate of the fastest growing mode, previously not understood, are derived analytically. The simplicity of the model suggests that shear dynamo action may be a generic property of sheared magnetohydrodynamic turbulence.Comment: Paper substantially rewritten, results changed (relative to v1). Revised versio

Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin?

Background: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. Patients and Methods: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 50 mg/m(2) on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). Results: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by greater than or equal to50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 non-responders (295 d; 95% CI: 285-445 vs. 174 d; 95% CI: 134-198; p = 0.022). Conclusion: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin

Sensitivity as outcome measure of androgen replacement: the AMS scale

BACKGROUND: The capacity of the AMS scale as clinical utility and as outcome measure still needs validation. METHODS: An open post-marketing study was performed by office-based physicians in Germany in 2004. We analysed data of 1670 androgen-deficient males who were treated with testosterone gel. The AMS scale was applied prior to and after 3 months treatment. RESULTS: The improvement of complaints under treatment relative to the baseline score was 30.7% (total score), 27.3% (psychological domain), 30.5% (somatic domain), and 30.7% (sexual domain), respectively. Patients with little or no symptoms before therapy improved by 9%, those with mild complaints at entry by 24%, with moderate by 32%, and with severe symptoms by 39% – compared with the baseline score. We showed that the distribution of complaints of testosterone deficient men before therapy almost returned to norm values after 12 weeks of testosterone treatment. Age, BMI, and total testosterone level at baseline did not modify the positive effect of androgen therapy. We also demonstrated that the AMS results can predict the independent (physician's) opinion about the individual treatment effect. Both, sensitivity (correct prediction of a positive assessment by the physician) and specificity (correct prediction of a negative assessment by the physician) were over 70%, if about 22% improvement of the AMS total score was used as cut-off point. CONCLUSION: The AMS scale showed a convincing ability to measure treatment effects on quality of life across the full range of severity of complaints. Effect modification by other variables at baseline was not observed. In addition, results of the scale can predict the subjective clinical expert opinion on the treatment efficiency

Generation of Magnetic Field by Combined Action of Turbulence and Shear

The feasibility of a mean-field dynamo in nonhelical turbulence with superimposed linear shear is studied numerically in elongated shearing boxes. Exponential growth of magnetic field at scales much larger than the outer scale of the turbulence is found. The charateristic scale of the field is l_B ~ S^{-1/2} and growth rate is gamma ~ S, where S is the shearing rate. This newly discovered shear dynamo effect potentially represents a very generic mechanism for generating large-scale magnetic fields in a broad class of astrophysical systems with spatially coherent mean flows.Comment: 4 pages, 5 figures; replaced with revised version that matches the published PR