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The intestine is extremely sensitive to ischemic preservation and reoxygenation injury. Current vascular perfusion and cold storage with University of Wisconsin (UW) solution neglect the intestinal lumen and the ongoing mucosal metabolism during hypothermia. This study was designed to test the effects of luminal preservation with an alternative preservation solution in addition to the common vascular flush with UW solution on graft viability after preservation and ex vivoreoxygenation.

The time distribution of injuries is not random. To assess the potential impact of weather and the phase of the moon on accidents, adjustment for known periodic and nonperiodic factors may be important. We compared the incidence of injuries with quantitative and qualitative weather variables as well as the lunar cycle, after correction for calendar and holiday-related factors.

Our aim in this study was to compare prognostic models based on laboratory tests with a model including imaging information in small-cell lung cancer.

Background/Aims: The aim of the study was to compare the serum response of regeneration factors and acute phase proteins in patients treated with partial hepatectomy or cryosurgery.

A Correction has been published for this article in Statistics in Medicine 2001; 20:982. In clinical trials where patients are randomized between two treatment arms, not all patients comply with the treatment they were randomly assigned to. The reasons for (non)compliance may be associated with the outcome variable and thereby act as confounders. The standard way of analysing such trials is by the ‘intention-to-treat’ principle, which allows the use of permutation tests. Conclusions drawn from such tests do not depend on untested assumptions such as absence of confounding. However, this approach may yield biased estimators for the causal effects of treatments. We consider the estimation of such effects for clinical trials where non-compliers can be considered to have switched to the other trial arm. The most important example of this is the placebo-controlled clinical trial where no substantial placebo effects are anticipated. We consider the situation where the relationship between compliance, and thus treatment received, and outcome is influenced by unobserved confounders. The residual of the regression of the actual treatment indicator variable on the randomization arm indicator variable is shown to ‘intercept’ the effect of such confounders. Inclusion of this residual in a multivariate analysis, in conjunction with the treatment indicator variable, should thus adjust for confounding. Examples are given. In those examples, the results are similar to those obtained by more complex methods. Copyright © 2000 John Wiley & Sons, Ltd.

A Correction has been published for this article in

The purpose of this study was to develop a model that predicts the outcome of su pervised exercise for intermittent claudication. The authors present an example of the use of autoregressive logistic regression for modeling observed longitudinal data. Data were collected from 329 participants in a six-month exercise program. The levels of the polytomous outcome variable correspond to states they defined in a Markov de cision model comparing treatment strategies for intermittent claudication. Autoregres sive logistic regression can be used to fit multistate transition models to observed longitudinal data with standard statistical software. The technique allows exploration of alternative assumptions about the dependence in the outcome series and provides transition probabilities for different covariate patterns. Of the alternatives examined, a Markov model including two preceding responses, time, age, ankle brachial index, and duration of disease best described the data. Key words: longitudinal data analysis; autoregressive models; logistic regression; Markov models; peripheral arterial occlu sive disease; intermittent claudication; exercise. (Med Decis Making 1998;18:52- 60)

OBJECTIVE: To evaluate whether including a test for faecal calprotectin, a sensitive marker of intestinal inflammation, in the investigation of suspected inflammatory bowel disease reduces the number of unnecessary endoscopic procedures. Design Meta-analysis of diagnostic accuracy studies. DATA SOURCES: Studies published in Medline and Embase up to October 2009. Interventions reviewed Measurement of faecal calprotectin level (index test) compared with endoscopy and histopathology of segmental biopsy samples (reference standard). Inclusion criteria Studies that had collected data prospectively in patients with suspected inflammatory bowel disease and allowed for construction of a two by two table. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data to account for a possible negative correlation within studies. RESULTS: 13 studies were included: six in adults (n=670), seven in children and teenagers (n=371). Inflammatory bowel disease was confirmed by endoscopy in 32% (n=215) of the adults and 61% (n=226) of the children and teenagers. In the studies of adults, the pooled sensitivity and pooled specificity of calprotectin was 0.93 (95% confidence interval 0.85 to 0.97) and 0.96 (0.79 to 0.99) and in the studies of children and teenagers was 0.92 (0.84 to 0.96) and 0.76 (0.62 to 0.86). The lower specificity in the studies of children and teenagers was significantly different from that in the studies of adults (P=0.048). Screening by measuring faecal calprotectin levels would result in a 67% reduction in the number of adults requiring endoscopy. Three of 33 adults who undergo endoscopy will not have inflammatory bowel disease but may have a different condition for which endoscopy is inevitable. The downside of this screening strategy is delayed diagnosis in 6% of adults because of a false negative test result. In the population of children and teenagers, 65 instead of 100 would undergo endoscopy. Nine of them will not have inflammatory bowel disease, and diagnosis will be delayed in 8% of the affected children. CONCLUSION: Testing for faecal calprotectin is a useful screening tool for identifying patients who are most likely to need endoscopy for suspected inflammatory bowel disease. The discriminative power to safely exclude inflammatory bowel disease was significantly better in studies of adults than in studies of children.

Acute myeloid leukemia (AML) is a disease with a poor prognosis. At this moment conventional chemotherapy is the gold standard for the treatment of AML. It is demonstrated that AML cells express VEGFA and VEGFC as well as KDR (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. The present study investigates the role of PTK787/ZK 222584, a potent inhibitor of VEGF receptor tyrosine kinases, upon leukemic cell death, and the possibility of an additional effect upon cell death achieved by a conventional chemotherapeutic drug Amsacrine. In 3 AML-cell lines and 33 pediatric AML patient samples we performed total cell kill assays to determine the percentage of cell death achieved by PTK787/ZK 222584 (5–100 μM) and/or Amsacrine (0.001–2 μg/ml). Both drugs induced AML cell death. The LC50 values (drug concentration needed to kill 50% of the leukemic cells) for HL-60, TF-1 and THP-1 were 27 μM, 49 μM and 24 μM respectively. An excellent survival was seen on a KDR-negative cell line demonstrating that the cell death induced by PTK787/ZK 222584 is not a toxic effect. The primary blasts were overall 5–10 times more sensitive to PTK787/ZK 222584 than the cell lines, with a median LC50 value of 5.1 μM. Patient samples with a LC50 value below the median did not differ from patients above the median regarding age, sex, FAB classification or WBC count. With a response surface analysis we investigated the additional effect of PTK787/ZK 222584 upon cell death achieved by Amsacrine; we estimated the concentration combinations resulting in the same cell survival. We could show that, in cell lines as well as in primary AML blasts, the concentration of Amsacrine can be lowered and replaced for a certain dose of the potentially less toxic VEGFR inhibitor to achieve the same percentage of leukemic cell death. This study shows that PTK787/ZK 222584 might have more clinical potential in AML when combined with chemotherapy, e.g. Amsacrine. In addition, it is known from literature that topoisomerase inhibitors, e.g. Amsacrine, can cause treatment related AMLs. Moreover, many survivors of childhood or adolescent cancer experience treatment related cardiovascular complications that can impair their quality of life years after treatment. Therefore, reduction of complications and long-term effects of chemotherapy is warranted and might be achieved by lowering dosages of Amsacrine and replace it by other drugs with a lower toxicity profile, such as PTK787/ZK 222584.

Acute myeloid leukemia (AML) is a disease with a poor prognosis. At this moment conventional chemotherapy is the gold standard for the treatment of AML. It is demonstrated that AML cells express VEGFA and VEGFC as well as KDR (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. The present study investigates the role of PTK787/ZK 222584, a potent inhibitor of VEGF receptor tyrosine kinases, upon leukemic cell death, and the possibility of an additional effect upon cell death achieved by a conventional chemotherapeutic drug Amsacrine. In 3 AML-cell lines and 33 pediatric AML patient samples we performed total cell kill assays to determine the percentage of cell death achieved by PTK787/ZK 222584 (5–100 μM) and/or Amsacrine (0.001–2 μg/ml). Both drugs induced AML cell death. The LC50 values (drug concentration needed to kill 50% of the leukemic cells) for HL-60, TF-1 and THP-1 were 27 μM, 49 μM and 24 μM respectively. An excellent survival was seen on a KDR-negative cell line demonstrating that the cell death induced by PTK787/ZK 222584 is not a toxic effect. The primary blasts were overall 5–10 times more sensitive to PTK787/ZK 222584 than the cell lines, with a median LC50 value of 5.1 μM. Patient samples with a LC50 value below the median did not differ from patients above the median regarding age, sex, FAB classification or WBC count. With a response surface analysis we investigated the additional effect of PTK787/ZK 222584 upon cell death achieved by Amsacrine; we estimated the concentration combinations resulting in the same cell survival. We could show that, in cell lines as well as in primary AML blasts, the concentration of Amsacrine can be lowered and replaced for a certain dose of the potentially less toxic VEGFR inhibitor to achieve the same percentage of leukemic cell death. This study shows that PTK787/ZK 222584 might have more clinical potential in AML when combined with chemotherapy, e.g. Amsacrine. In addition, it is known from literature that topoisomerase inhibitors, e.g. Amsacrine, can cause treatment related AMLs. Moreover, many survivors of childhood or adolescent cancer experience treatment related cardiovascular complications that can impair their quality of life years after treatment. Therefore, reduction of complications and long-term effects of chemotherapy is warranted and might be achieved by lowering dosages of Amsacrine and replace it by other drugs with a lower toxicity profile, such as PTK787/ZK 222584.