Mortality due to gastroenteritis of unknown etiology in the United States

Gastroenteritis of unknown etiology (GUE) is a significant cause of mortality in the United States. In the present study, the demographic and medical characteristics of people who died of GUE were examined, using the 1995-1997 Multiple Cause of Death files to calculate GUE death rates and proportionate mortality ratios. There were 13,153 GUE deaths during the period, or approximately 4400 deaths per year. Death rates were highest among infants and elderly persons, especially nursing home residents, and increased during the winter months. Compared with all decedents, GUE decedents were more likely to have certain other medical conditions, including bacteremia, volume depletion, renal failure, and human immunodeficiency virus/acquired immunodeficiency syndrome. Fatal GUE often appeared to be infectious in origin, but death certificates provide insufficient information to determine whether the causative agents were unknown or foodborne. The accuracy of GUE reporting on death certificates and the etiology of fatal GUE merit further investigation.     

Clonal T cell-mediated cyclic thrombocytopenia

Cyclic thrombocytopenia is a rare disorder characterized by periodic platelet count fluctuations of unknown aetiology. We report on a female patient with cyclic changes of platelet counts ranging from 6 x 10(9)/l to 753 x 10(9)/l in 4-week intervals. Platelet counts were inversely correlated to thrombopoietin levels suggesting production failure. Reticulocyte counts and neutrophil counts showed similar, but less prominent, fluctuations. Clonal T-cell receptor rearrangement was detected in bone marrow samples as well as in peripheral blood. Cell typing of blood lymphocytes revealed a relative increase in CD3+ T cells. Treatment with cyclosporine A resulted in a substantial improvement of platelet counts. Taken together, we provide evidence for clonal T-cell mediated bone marrow failure with cyclic impairment of thrombopoiesis responsive to cyclosporine therapy.     

Effects of covariates: a summary of Group 5 contributions

This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13) related to the use of covariates in genetic analysis. Seven papers are summarized, five of which analyzed the Framingham Heart Study Data, and two the simulated data. Five papers examined the role of covariates in linkage analysis, using a variety of statistical approaches including affected sibling pair analysis, conditional logistic regression, and variance components methods. One paper examined the impact of covariates on family-based association analysis. In each of these papers, the detection of genetic effects could be influenced by the incorporation of covariates. The final paper examined the role of transmission ratio distortion in the analysis of complex traits and the role of covariates in the variability in transmission ratio distortion. While each paper takes a different approach to the genetic analysis of complex traits, a common thread running through each is that the inclusion of covariates can have a substantial impact on the results of the analysis. Care must be taken to understand how the covariates are being used in each analysis, what assumptions are being made, and how these assumptions might affect the results and their interpretation. Finally, the results of Group 5 studies show that inclusion of covariates can increase the power to detect genes for complex traits, and has the potential to advance an understanding of the role of genes in these complex traits.     

Measurements of HCV neutralizing antibodies and of HCV-specific CD4+ and CD8+ cells using hepatitis C virus pseudo-particles (HCVpp)

BackgroundFor the medical management, it would be of great relevance to get a diagnostic marker predicting the outcome of infection.ObjectivesFor this purpose, the envelope antigens of the individual HCV strain in a patient was tested for their capacity to induce neutralizing antibodies and cytotoxic T lymphocytes.Study designA system for the measurement of neutralizing antibodies as well as for the stimulation of a HCV-specific T-cell response using pseudo-typed HCV particles (HCVpp) was established. A report on results of a pilot study conducted with blood specimens of 19 chronically infected patients is also presented.ResultsNeutralization of HCVpp could be measured in nearly all HCV sero-positive patient samples. Nevertheless, in more than half of the patient samples (11/19), no HCV-specific CD4+ response was detectable. In addition, HCV-specific CD8+ response was measurable in most of the patients when HCVpp were used for T-cell stimulation. Although the same antigens (HCVpp) were used, there was no relevant correlation between neutralization titers and T-cell response.ConclusionOur study shows that HCVpp are appropriate antigens for specific stimulation of lymphocytes as well as for the investigation of antibody neutralization activity.     

Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials.

Although retroviral vectors are one of the most widely used vehicles for gene transfer, there is no uniformly accepted pre-clinical model defined to assess their safety, in particular their risk related to insertional mutagenesis. In the murine pre-clinical study presented here, 40 test and 10 control mice were transplanted with ex vivo manipulated bone marrow cells to assess the long-term effects of the transduction of hematopoietic cells with the retroviral vector MSCV-MGMT(P140K)wc. Test mice had significant gene marking 8-12 months post-transplantation with an average of 0.93 vector copies per cell and 41.5% of peripheral blood cells expressing the transgene MGMT(P140K), thus confirming persistent vector expression. Unexpectedly, six test mice developed malignant lymphoma. No vector was detected in the tumor cells of five animals with malignancies, indicating that the malignancies were not caused by insertional mutagenesis or MGMT(P140K) expression. Mice from a concurrent study with a different transgene also revealed additional cases of vector-negative lymphomas of host origin. We conclude that the background tumor formation in this mouse model complicates safety determination of retroviral vectors and propose an improved study design that we predict will increase the relevance and accuracy of interpretation of pre-clinical mouse studies.     

Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients—a double-blind,randomised, prospective,controlled trial

Background Central venous catheters (CVCs) are essential for the intensive care of patients with haematological illness. Catheter-related infections (CRI) are an important problem in modern medicine, which may lead to life-threatening situations, to prolonged hospitalisation and increased cost. In immunocompromised patients suffering from haemato-oncological diseases, CRI is a significant factor for adverse outcome. Several clinical studies have shown that CVCs coated with antiseptics such as chlorhexidine and silver-sulfadiazine (CHSS) reduce the risk of catheter-related bacteraemia. Most studies, however, were performed on intensive care patients not suffering from chemotherapy-induced immunosuppression.Patients and methods A prospective double-blind, randomised, controlled trial was performed to investigate the effectiveness of CHSS-coated catheters in haemato-oncological patients. A total number of 184 catheters (median duration of placement, 11 days) were inserted into 184 patients (male 115, female 69), of which 90 were antiseptically coated. After removal, all catheters were investigated for bacterial growth.Main results Catheters coated with CHSS were effective in reducing the rate of significant bacterial growth on either the tip or subcutaneous segment (26%) compared to control catheters (49%). The incidence of catheter colonisation was also significantly reduced (12% coated vs 33% uncoated). Data obtained show a significant reduction of catheter colonisation in CHSS catheters. There was no significant difference in the incidence of catheter-related bacteraemia (3% coated vs 7% uncoated). However, due to the overall low rate of CRI, we could not observe a significant reduction in the incidence of catheter-related bacteraemia.Conclusion Our data show that the use of CHSS catheters in patients with haematological malignancy reduces the overall risk of catheter colonisation and CRI, although the incidence of catheter-related bacteremia was similar in both groups.     

CD133-enriched CD34(-) (CD33/CD38/CD71)(-) cord blood cells acquire CD34 prior to cell division and hematopoietic activity is exclusively associated with CD34 expression

We compared the cell division behavior of CD34(-) and CD34(+) (CD33/CD38/CD71)-negative (Lin(-)) CD133(+) cord blood cells stimulated with the cytokines Flt3-ligand, stem cell factor, and thrombopoietin. Within a 4-day time frame, Lin(-)CD34(-) CD133(+) (CD34(-)) cells underwent more cell divisions in serum-free culture than their Lin(-)CD34(+) CD133(+) (CD34(+)) counterparts. The majority of CD34(-) cells acquired expression of CD34 in vitro, including most undivided cells. Moreover, hematopoietic activity from both CD34(-) and CD34(+) cells was exclusively retained within the cell fraction expressing CD34 after 4 days in culture. Most strikingly, in cultures from Lin(-)CD34(-) cells hematopoietic activity was associated with the fraction of divided cells, whereas in cultures of CD34(+) cells, hematopoietic activity associated with the undivided cell fraction. Therefore, clonogenic CD34(+) cells either do not divide or lose their clonogenic capacity upon cell division in vitro, while CD34(-) cells divide and retain this capacity under the same specific conditions. In conclusion, we demonstrate that CD133-enriched Lin(-)CD34(-) cord blood cells acquire CD34 prior to cell division and that long-term hematopoietic activity is associated exclusively with expression of CD34.     

Assessment of salivary cortisol as stress marker in ambulance service personnel: comparison between shifts working on mobile intensive care unit and patient transport ambulance

Purpose  

The aim of this study was to describe and compare salivary cortisol of ambulance personnel on days with different work demands as well as to correlate the individual perception of demands to the physiological outcome cortisol.     

Rats with hippocampal lesion show impaired learning and memory in the ziggurat task: a new task to evaluate spatial behavior

Spatial tasks are widely used to determine the function of limbic system structures in rats. The present study used a new task designed to evaluate spatial behavior, the ziggurat task (ZT), to examine the performance of rats with widespread hippocampal damage induced by N-methyl-d-aspartic acid (NMDA). The task consisted of an open field containing 16 identical ziggurats (pyramid shaped towers) arranged at equal distances. One of the ziggurats was baited with a food reward. The task required rats to navigate through the open field by using a combination of distal and/or proximal cues in order to locate the food reward. The ability to acquire and recall the location of the goal (baited) ziggurat was tested in consecutive training sessions of eight trials per day for 10 days. The location of the goal ziggurat was changed every second day, requiring the rats to learn a total of five different locations. Several parameters, including latency to find the target, distance traveled, the number of visits to non-baited ziggurats (errors), and the number of returns were used as indices of learning and memory. Control rats showed a significant decrease in distance traveled and reduced latency in locating the goal ziggurat across trials and days, suggesting that they learned and remembered the location of the goal ziggurat. Interestingly, the hippocampal-damaged group moved significantly faster, and traveled longer distances compared to the control group. Significant differences were observed between these groups with respect to the number of errors and returns on test days. Day 11 served as probe day, in which no food reward was given. The controls spent more time searching for the food in the previous training quadrant compared to the hippocampal group. The findings demonstrate that the ZT is a sensitive and efficient dry task for measuring hippocampus-dependent spatial performance in rats requiring little training and not associated with some of the disadvantages of water tasks.