Systematic reviews and meta-analyses are the cornerstones of evidence-based medicine and inform treatment, diagnosis, or prevention of individual patients as well as policy decisions in health care. Statistical methods for the meta-analysis of intervention studies are well established today. Meta-analysis for diagnostic accuracy trials has also been a vivid research area in recent years, which is especially due to the increased complexity of their bivariate outcome of sensitivity and specificity. The situation is even more challenging when single studies report a full ROC curve with several pairs of sensitivity and specificity, each pair for a different threshold. Researchers frequently ignore this information and use only 1 pair of sensitivity and specificity from each study to arrive at meta-analytic estimates. Although methods to deal with the full information have been proposed, they have some disadvantages, eg, the numbers or values of thresholds have to be identical across studies, or the precise values of thresholds are ignored. We propose an approach for the meta-analysis of full ROC curves including the information from all thresholds by using bivariate time-to-event models for interval-censored data with random effects. This approach avoids the problems of previous methods and comes with the additional advantage that it allows for various distributions of the underlying continuous test values. The results from a small simulation study are given, which show that the approach works well in practice. Furthermore, we illustrate our new model using an example based on the population-based screening for type 2 diabetes mellitus.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX).In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n5145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group).The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Alveolar type II pneumocytes (PII) were studied in 12 human donor lungs perfused with modified Euro-Collins solution during single-lung transplantation (SLTx). While one lung was transplanted, the contralateral donor lung (cDL) was fixed at the time of SLTx for examination by electron microscopy, stereology, and microanalysis. Three groups were then formed: group A (n = 7), cDL without contusions, uneventful early postoperative course; group B (n = 3), cDL with conclusions, uneventful early postoperative course; group C (n = 2), cDL without contusions, early postoperative respiratory dysfunction. The major findings were that the presence of contusions had no effect on PII ultrastructure and that intracellular surfactant-storing lamellar bodies of cDL in group C were characterized by a higher volume-to-surface ratio (VsR) and larger area per cell profile than group A. Correlation analysis based on pooled data (groups A and C) showed that ischaemic time had little effect on PII ultrastructure and bore no relationship to postoperative clinical variables. The duration of preoperative donor intubation had a pronounced influence on ultrastructure and postoperative clinical variables. The stereologically estimated amount of intracellular surfactant and mitochondrial VsR were the only ultrastructural parameters that were significantly associated with early postoperative oxygenation. Lamellar bodies were the only ultrastructural components found to have a significant relationship to postoperative intubation time. The ultrastructural integrity of type II pneumocytes of human donor lungs is an important determinant of early respiratory function following clinical lung transplantation.

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Objective: The goal of the present study was to examine the ability of failing myocardium to respond to enhanced preload with an Ž . increase in force development. Methods: The effect of various preload conditions 2.5-15 mN on force development was studied in Ž . right ventricular trabeculae carneae from explanted human failing hearts with ischemic cardiomyopathy ICM, n s 5, 42 preparations or Ž . idiopathic dilated cardiomyopathy DCM, n s 9, 77 preparations . To determine the severity of cardiac impairment we measured the Ž to length of maximal force development from 3.7 " 0.5 ICM and 2.7 " 0.4 DCM to 8.3 " 0.9 and 6.5 " 0.8 mNrmm , respectively Ž . Ž. The Frank-Starling mechanism is preserved in terminally failing human hearts irrespective of the underlying etiology. We found no relation between the severity of cardiac impairment as assessed by either ANP expression or the ISOrCa 2q ratio and the ability of failing human myocardium to respond to enhanced preload with an increase in force development. q 1998 Elsevier Science B.V.

Background: Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Objective: Evaluation of methods for the rapid diagnosis of CMV pneumonitis. Methods: The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. Results: In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. Conclusions: PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis.

Two to 7.5 hours of cold ischemia following ECS preservation do not deteriorate the fine structure of type II pneumocytes of human donor lungs. For reliable assessment of fine structural variations, morphometric parameters are required that are independent of variations in cell size.

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