Biomedical subjects

M Greiner

Publications and source records attributed to M Greiner.

At least 19 recordsLinked to original sources

PubMed2001

A survival analysis of trypanosomosis diagnostic-test performance under natural infection challenge.

Little is known about the time-to-first detection and the time difference (TD) between first parasitological and first serological diagnosis of Trypanosoma spp. infections under natural infection challenge in cattle. The objective of our study was to estimate these measures of "longitudinal aspects" of diagnostic performance and to investigate potential biological factors. Emphasis was on diagnosis at the genus level (Trypanosoma spp.). Twelve N'Dama, 12 Gobra zebu and 12N'DamaxGobra (F1) crossbred cattle (all animals non-infected at the start of the experiment, six male and six female animals in each cohort) were exposed to natural high tsetse challenge in the Niamina East area in The Gambia [Acta Trop. 71 (1998) 57]. The animals were investigated parasitologically (detection of trypanosomes by buffy-coat technique), serologically (detection of T. brucei, T. congolense and T. vivax antigen by enzyme-linked immunosorbent assay (ELISA)) and clinically (packed-cell volume, PCV) over a period of 180 days. The time-to-first detection of trypanosomes, trypanosomal antigen (cut-off as suggested by test supplier) and drop in PCV (subject-based cut-off values) were recorded as outcomes of interest. Thus, incidence was both parasitologically (I(p)), serologically (I(s)) and clinically (I(c)). Recurrent events were not considered. The TD between first parasitological and first serological detection was established as I(s) time minus I(p) time. The effect of breed and sex on the time-to-first detection and on TD was investigated using Cox (proportional hazard) regression and ANOVA, respectively. We found that time-to-first parasitological detection of trypanosomosis in N'Dama animals was significantly longer than in the two other breeds (Cox regression, P=0.002). A similar but less-strong (P=0.063) effect of breed on time-to-first detection of trypanosomal antigen was found, whereas no breed effect was observed for clinical detection (P=0.432). Sex had no effect in all detection systems. The TD varied between -56 and 115 (mean 28). Marked differences among breeds and between sexes were not observed (ANOVA, P=0.8). We suggest that incidence studies are more suitable for detecting risk factors for animal trypanosomosis than prevalence-based (cross-sectional) studies because the latter often result in misinterpretation of factors that increase the survival time with infection as risk factors.

Animals↗

PubMed2001

Optics with an atom laser beam.

We report on the atom optical manipulation of an atom laser beam. Reflection, focusing, and its storage in a resonator are demonstrated. Precise and versatile mechanical control over an atom laser beam propagating in an inhomogeneous magnetic field is achieved by optically inducing spin flips between atomic ground states with different magnetic moment. The magnetic force acting on the atoms can thereby be effectively switched on and off. The surface of the atom optical element is determined by the resonance condition for the spin flip in the inhomogeneous magnetic field. More than 98% of the incident atom laser beam is reflected specularly.

Journal Article↗

PubMed2001

The nuclear export receptor Xpo1p forms distinct complexes with NES transport substrates and the yeast Ran binding protein 1 (Yrb1p).

Xpo1p (Crm1p) is the nuclear export receptor for proteins containing a leucine-rich nuclear export signal (NES). Xpo1p, the NES-containing protein, and GTP-bound Ran form a complex in the nucleus that translocates across the nuclear pore. We have identified Yrb1p as the major Xpo1p-binding protein in Saccharomyces cerevisiae extracts in the presence of GTP-bound Gsp1p (yeast Ran). Yrb1p is cytoplasmic at steady-state but shuttles continuously between the cytoplasm and the nucleus. Nuclear import of Yrb1p is mediated by two separate nuclear targeting signals. Export from the nucleus requires Xpo1p, but Yrb1p does not contain a leucine-rich NES. Instead, the interaction of Yrb1p with Xpo1p is mediated by Gsp1p-GTP. This novel type of export complex requires the acidic C-terminus of Gsp1p, which is dispensable for the binding to importin beta-like transport receptors. A similar complex with Xpo1p and Gsp1p-GTP can be formed by Yrb2p, a relative of Yrb1p predominantly located in the nucleus. Yrb1p also functions as a disassembly factor for NES/Xpo1p/Gsp1p-GTP complexes by displacing the NES protein from Xpo1p/Gsp1p. This Yrb1p/Xpo1p/Gsp1p complex is then completely dissociated after GTP hydrolysis catalyzed by the cytoplasmic GTPase activating protein Rna1p.

Active Transport, Cell Nucleus↗

PubMed2000

Preface

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Journal Article↗

PubMed2000

Epidemiologic issues in the validation of veterinary diagnostic tests.

In this review, we critically discuss the objectives, methods and limitations of different approaches for the validation of diagnostic tests. We show (based on published data and our own experiences) that estimates for the diagnostic sensitivity and specificity may vary among populations and/or subpopulations of animals, conditional on the distribution of influential covariates. Additional variability in those parameter estimates may be attributable to the sampling strategy. The uncertainty about diagnostic parameters is of concern for the decision-maker in the context of clinical diagnosis or quantitative risk assessment as well as for the epidemiologist who uses test data for prevalence estimation or risk-factor studies. Examples for the calculation of diagnostic parameters are presented together with bias-avoidance strategies. We suggest guidelines for an epidemiologic approach to test validation of veterinary diagnostic tests.

Animal Diseases↗

PubMed2000

Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests.

We review the principles and practical application of receiver-operating characteristic (ROC) analysis for diagnostic tests. ROC analysis can be used for diagnostic tests with outcomes measured on ordinal, interval or ratio scales. The dependence of the diagnostic sensitivity and specificity on the selected cut-off value must be considered for a full test evaluation and for test comparison. All possible combinations of sensitivity and specificity that can be achieved by changing the test's cut-off value can be summarised using a single parameter; the area under the ROC curve. The ROC technique can also be used to optimise cut-off values with regard to a given prevalence in the target population and cost ratio of false-positive and false-negative results. However, plots of optimisation parameters against the selected cut-off value provide a more-direct method for cut-off selection. Candidates for such optimisation parameters are linear combinations of sensitivity and specificity (with weights selected to reflect the decision-making situation), odds ratio, chance-corrected measures of association (e. g. kappa) and likelihood ratios. We discuss some recent developments in ROC analysis, including meta-analysis of diagnostic tests, correlated ROC curves (paired-sample design) and chance- and prevalence-corrected ROC curves.

Animal Diseases↗

PubMed2000

Application of diagnostic tests in veterinary epidemiologic studies.

Important applications of diagnostic tests in non-clinical areas of veterinary medicine include surveillance, monitoring or screening for disease, prevalence estimation, and risk-factor studies. In this review, we address the processing and analysis of diagnostic data with special emphasis on serological data from enzyme-linked immunosorbent assays (ELISAs). We describe methods that are used to adjust for misclassification (imperfect sensitivity and specificity) in the different applications of diagnostic tests. These methods often have limitations attributable to the uncertainty of sensitivity and specificity estimates. We review descriptive and analytical statistical methods that allow adequate presentation of non-clinical diagnostic data.

Animal Diseases↗

PubMed2000

Helicobacter pylori infection in wild-type and cytokine-deficient C57BL/6 and BALB/c mouse mutants.

Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytokines are thought to play a substantial role in the control of H. pylori infection. To determine the importance of T helper (Th) cytokines and background genes we investigated the natural course of H. pylori infection in BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)-4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H. pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/-) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4 deficiency had no detectable effect on H. pylori recovery rates from either strain of mice. Our data suggest a protective role of IFN-gamma by mediating inflammation in murine H. pylori infection. In addition, our data emphasize that background genes which differ between BALB/c and C57BL/6 mice regulate the clearance of H. pylori.

Animals↗

PubMed2000

Impact of tsetse control on the age-specific prevalence of trypanosomosis in village cattle in southeast Uganda.

The prevalence of trypanosomosis, mean packed cell volume and anti-trypanosomal antibody levels in village cattle of different age groups (< 0.5 year, 0.5-2 years, > 2-5 years and > 5 years) in the areas with tsetse control were compared with those of corresponding age groups in areas without tsetse control in Tororo, southeast Uganda. The prevalence of trypanosomosis in cattle in the age groups of 0.5-2 years, > 2-5 years and > 5 years in the areas with tsetse control was significantly lower than in cattle in similar age groups in the areas without tsetse control (p < 0.5). Trypanosoma vivax was the most predominant Trypanosoma species in the areas with tsetse control, while T. congolense was the most predominant species in the areas without tsetse control. The mean Trypanosoma antibody levels in cattle in the age groups < 0.5 year, 0.5-2 years and > 2-5 years in the areas with tsetse control were significantly lower than those of the similar age groups in the areas without tsetse control (p < 0.5). The mean PCV values for cattle in the age groups 0.5-2 years, > 2-5 years and > 5 years from the areas with tsetse control were significantly higher than those of the similar age groups in the areas without tsetse control. Tsetse control appeared to have a considerable impact on the prevalence of trypanosomosis, distribution of Trypanosoma species, specific antibody levels and the packed cell volume of cattle in the different age groups.

Age Factors↗

PubMed2000

Placebo-controlled study of gabapentin treatment of panic disorder.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder. One hundred three patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 600 and 3,600 mg/day) or placebo for 8 weeks. No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale (PAS) (p = 0.606). A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure (PAS score > or = 20). In this population, the gabapentin-treated patients showed significant improvement in the PAS change score (p = 0.04). In patients with a PAS score of 20 or greater, women showed a greater response than men regardless of treatment. Adverse events were consistent with the known side effect profile of gabapentin and included somnolence, headache, and dizziness. One patient experienced a serious adverse event during the study. No deaths were reported. The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder.

Acetates↗

PubMed2000

Increased seizures after discontinuing carbamazepine: results from the gabapentin monotherapy trial.

Studies in patients with epilepsy undergoing telemetry evaluation for surgery have suggested that discontinuation of carbamazepine (CBZ) is associated with increased seizures. The period of observation in that setting, however, was limited to a few days. The authors reviewed the occurrence of seizures in patients with epilepsy who had all their antiepileptic medications discontinued during an 8-week period, converted to gabapentin monotherapy, and observed for 26 weeks as part of the gabapentin trial #945-082. Two hundred and seventy-five patients were enrolled. Kaplan-Meier estimates of time to exit for all patients showed that 18% of patients previously treated with CBZ completed the study as compared with 30% of the patients receiving other antiepileptic medications. Increase in the frequency of seizures was maximal in the 2 weeks following CBZ discontinuation. Seizures increased both in frequency and severity but no new seizure types were observed. The findings in this study show that removal of CBZ is associated with increased frequency of seizures in patients with a previous history of epilepsy with incompletely controlled seizures. The period of maximal increase was the first 2 weeks after CBZ discontinuation.

Acetates↗

PubMed2000

[Planning of epidemiologic studies using the example of parasitic diseases].

Epidemiology is concerned with the study of diseases and risk factors for diseases in populations. Livestock related studies require that the term disease is extended to cover all conditions that directly or indirectly may affect the economic, social and ecological value of livestock or constitute a public health risk. The objectives of epidemiologic studies range from the quantification of traits, e.g., prevalence of a disease in a population (descriptive approach), to the analysis of correlation between diseases and putative risk factors (analytic approach). The type of epidemiologic study must be selected accordingly. In this paper we present the most important types of epidemiologic studies using example data. Our aim is to give an orientation for the planning of epidemiologic studies.

Animals↗

PubMed1999

Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder.

BACKGROUND: Based on the induction of panic-like symptoms by infusion of cholecystokinin (CCK) peptide in normals and panic disorder patients, it has been proposed that CCK may play a role in the disease mechanisms underlying anxiety disorders. Selective antagonists of CCK-B receptors can block the challenge-induced symptoms in a dose-dependent manner, leading to the hypothesis that these compounds may have anxiolytic effects. METHODS: A randomized, double-blind study was carried out to compare the effects of placebo with CI-988, a selective antagonist of the CCK-B receptors. Following a one-week placebo lead-in, patients with Panic Disorder with or without Agoraphobia received either placebo or CI-988 100 mg TID for six weeks. Panic attacks were recorded by a daily diary method. RESULTS: A total sample of 88 patients was planned but and interim analysis was carried out when about half the patients had been enrolled (n = 41). All patients improved during treatment and no difference in the weekly rate of panic attacks was seen between the treatment groups. The study was terminated at this point due to the remote likelihood of showing a treatment difference. CONCLUSIONS: CI-988 was not superior to placebo in reducing panic attacks. Several explanations are possible, including the poor pharmacokinetic characteristics of CI-988 which may make it unsuitable to test the CCK hypothesis of anxiety.

Adolescent↗

PubMed1999

Serosurvey on theileriosis in Awassi sheep in Syria.

A serological survey using indirect fluorescent antibody test (IFAT) for Theileria spp. infection of sheep has been carried out from 1994 to 1997 in the provinces Daraa, Hama, Homs and Latakia in Syria. The results revealed a mean seroprevalence of 59.9% without significant differences between years (p = 0.57) and provinces (p = 0.126).

Animals↗

PubMed1999

Altered gallbladder bile acidification with long-term total parenteral nutrition.

BACKGROUND: An important function of the gallbladder is to acidify and concentrate bile. Acidification helps protect against the precipitation of calcium salts, which promote gallstone formation. Altered acidification may result in pigment gallstones. We investigated gallbladder composition in a model of TPN-associated pigment gallstones to test whether changes in acidification may be important in this gallstone model. MATERIALS AND METHODS: Ten miniswine were intravenously fed for 21 to 27 days (mean 23 days). Ten fed pig chow with intravenous infusion of saline served as controls. Gallbladder and hepatic bile electrolytes, lipids, pH, and pCO2 were measured. RESULTS: All animals remained healthy and gained weight. Hepatic bile electrolytes and pH were similar among all animals. Pigs on TPN had a higher gallbladder pH and the [H+] was half the value of controls [8.1 +/- 1.6 x 10(-8) meq/liter (control) versus 3.9 +/- 0.7 x 10(-8) meq/liter (TPN)]. Gallbladder bile pCO2, sodium (Na), and potassium were higher in controls. Biliary lipids [bile salts (BS), phospholipids, and cholesterol] with TPN were decreased in both hepatic and gallbladder bile. CONCLUSIONS: Unlike short-term TPN where gallbladder pH and [BS] are similar, with long-term TPN pH is higher with lower [H+], [Na], and [BS]. Despite a presumed longer residence time in the gallbladder, intravenous feeding without oral intake results in gallbladder bile that is less concentrated and acidified. Enteral stimulation may be an important stimulus for gallbladder acidification and periods without feeding may promote gallstone formation by increasing the pH of gallbladder bile.

Animals↗

PubMed1999

Validation of the indirect MAP1-B enzyme-linked immunosorbent assay for diagnosis of experimental Cowdria ruminantium infection in small ruminants.

The major antigenic protein 1 fragment B (MAP1-B) enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Cowdria ruminantium infections was validated to determine cutoff values and evaluate its diagnostic performance with sheep and goat sera. Cowdria-infected populations consisted of 48 sheep and 44 goats, while the noninfected populations consisted of 64 sheep and 107 goats. Cutoff values were determined by two-graph receiver-operating characteristic (TG-ROC) curves. The cutoff value was set at 31 and 26.6% of the positive control reference samples for sheep and goat sera, respectively. The test's diagnostic performance was evaluated with measurements of the area under the concentration-time curve (AUC) of the ROC curves and by the valid range proportion (VRP). The AUCs were 0.978 for sheep sera and 0.989 for goat sera. The VRP for both sheep and goat sera was approximately 1.0. The intermediate range (IR), which defines results that are neither positive nor negative, was 0 for goat sera and 2.81 for sheep sera. In an ideal test, the AUC and VRP would be 1.0 and the IR would be 0. In this study these parameters were close to those of an ideal test. It is concluded that the MAP1-B ELISA is a useful test for the diagnosis of C. ruminantium infection in small ruminants.

Animals↗

PubMed1998

Prevalence estimation under heterogeneity in the example of bovine trypanosomosis in Uganda.

We examine variance estimators of a binomial parameter established under cluster sampling using data from a cross-sectional study of bovine trypanosomosis in Mukono County, Uganda. Fifty farms (referred to as clusters), were sampled with a total sample size of 487 cattle. Trypanosomes were found in 17.9% (87/487) of the total sample. The cluster-level (CL) prevalences were not homogeneously distributed. According to maximum-likelihood parameters established by mixture-distribution analysis, 18% of the cluster had 0% prevalence whereas 48% and 34% of the clusters could be allocated to subpopulations of clusters with mean prevalences 11.6% and 31.9% respectively. We show that this form of heterogeneity invalidates the applicability of the Beta distribution as a model for the distribution of CL prevalences. Furthermore, we provide empirical evidence for a variance inflation due to heterogeneity (inflation factor 2.07) that exceeds the design-based variance inflation due to clustering alone (inflation factor 1.82). The variance inflation due to heterogeneity is given in a closed form so that the approach can be conveniently applied to survey data that involve cluster sampling under heterogeneity.

Animals↗

PubMed1998

Altered intestinal immune system but normal antibacterial resistance in the absence of P-selectin and ICAM-1.

ICAM-1 and P-selectin are adhesion molecules that regulate leukocyte migration, extravasation to inflammatory sites, and other immune cell interactions. T cell-mediated resistance against acute infection with Listeria monocytogenes and chronic infection with Mycobacterium bovis Calmette-Guérin bacillus was investigated in mutant mice lacking P-selectin and/or ICAM-1. Mice deficient in P-selectin (Psel-/-), ICAM-1 (ICAM-/-), or the combination of both (Psel-/- x ICAM-/-) showed normal bacterial clearance, comparable delayed-type hypersensitivity reactions, and equivalent memory T cell responses. Additionally, the distribution of alpahbeta vs gammadelta T lymphocyte populations was examined. Normal lymphocyte distributions were noted in thymus, spleen, and blood, whereas mutant mice showed marked alterations in the intestinal intraepithelial (i-IEL) and lamina propria lymphocytes. Differences in i-IEL populations were reflected functionally by differential lytic activities and cytokine productions of i-IEL populations from mutant mice. Despite these changes within the mucosal immune system of mutant mice, their resistance against oral infection with L. monocytogenes was apparently unimpaired. These findings demonstrate that P-selectin and ICAM-1 are critically involved in the shaping of lymphocyte populations of the gut but have only a minor influence on systemic and regional host defense against intracellular bacteria.

Animals↗