PubMed Health⌕ Search

Biomedical subjects

M Greiner

Publications and source records attributed to M Greiner.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Inhibitory effect of 1alpha,25-dihydroxyvitamin D3 on allogeneic lymphocyte stimulation and Langerhans cell maturation.

1alpha,25-Dihydroxyvitamin D3 (calcitriol) has been shown to inhibit the proliferation of peripheral blood mononuclear cells induced by allogeneic Langerhans cells in a human mixed epidermal cell lymphocyte reaction. The potent antigen-presenting function of Langerhans cells is gained during culture. We tried to dissect the effect of calcitriol on lymphocyte proliferation and Langerhans cell maturation in a murine mixed epidermal cell lymphocyte reaction using unfractioned epidermal cells as a source for Langerhans cells. First, calcitriol was added upon setup of the mixed epidermal cell lymphocyte reaction using cultured epidermal cells as antigen-presenting cells, and this was found to inhibit the proliferation of lymphocytes in a time- and concentration-dependent manner. When calcitriol was added only during preculture of freshly isolated epidermal cells, the subsequent mixed epidermal cell lymphocyte reaction was also inhibited. In addition, the growth of keratinocytes and the production of granulocyte/macrophage colony-stimulating factor during preculture of epidermal cells was completely inhibited. Supplementation with this growth factor only partially restored the proliferative response of lymphocytes. These results suggest that calcitriol inhibits both the alloantigen-driven stimulation of naive T cell and Langerhans cells maturation. Further experiments with purified Langerhans cells are required to elucidate the mechanism of action of calcitriol on Langerhans cell maturation.

Animals↗
PubMed1998

Clinical follow-up examination after treatment of canine leishmaniasis.

In 16 dogs, the diagnosis of canine leishmaniasis could be detected by direct microscopic identification, by determination of the antibody titre or by PCR method (peripheral blood/bone marrow). On the basis of the clinical and laboratory diagnostic results 9 cases of the cutaneous type and 7 dogs of the combined cutaneous-visceral type (+ mono- or polyarthritis, hepatopathy and/or renal insufficiency as well as occular manifestation) have been classified. Therapy was: GLUCANTIME in 6 dogs, allopurinol in 3 dogs as single agent, combination-therapy GLUCANTIME and allopurinol in 7 dogs. During GLUCANTIME-treatment the following adverse reactions could be observed: general weakness, reduced food intake up to anorexia, vomiting and diarrhoea. Laboratory parameters showed sporadically leucopenia or pancreatitis. Adverse reactions during allopurinol therapy were: vomitus/diarrhoea or urine concrements. One dog with GLUCANTIME therapy, 2 dogs with allopurinol as well as 2 dogs with combination therapy are clinically symptom-free at the moment (peripheral blood and bone marrow: PCR negative). The remaining 11 patients showed a good to very good improvement of the clinical symptoms. However, since the peripheral blood respectively the bone marrow continue to be PCR positive, relapses have to be expected in these dogs.

Allopurinol↗
PubMed1998

PCR follow-up examination after treatment of canine leishmaniosis (CaL).

A study has been performed to investigate the usefulness of the polymerase chain reaction (PCR) for both the diagnosis and the follow-up after treatment of canine leishmaniosis (CaL). Blood samples (PBL) and/or bone marrow aspirates (BM) could be examined in a total of 18 confirmed cases of primary CaL. PBL was PCR-positive in 87%, whereas the BM was found to be positive in all cases (n=14) tested. PBL and BM from a total of 13 patients were submitted to PCR examinations after meglumine antimoniate (Glucantime) treatment. Only one dog showed a negative PCR after 2 treatment cycles (days 1-2: 50 mg/kg bw; days 3-10: 100 mg/kg bw). Examination of the PBL and BM after 15 months remained further PCR negative. All other dogs, from which four were pretreated with allopurinol up to 5 weeks, continued to be positive (92%) at least in the BM. Ten dogs could be monitored by means of the PCR after allopurinol treatment (2 x 10 mg/kg/bw/day/) either as a monodrug therapy in seven or as a successive combination with Glucantime in three cases. Two out of three dogs which showed good clinical improvement after daily administration for five weeks were likewise PCR negative in both the PBL and the BM. The four other dogs remained positive after the single therapy with allopurinol up to 5 weeks. A further three dogs were treated with allopurinol for 5 weeks, 6 and 20 month, respectively, after being clinically cured with Glucantime. Two of them were PCR negative in the PBL and BM after 5 weeks and 20 month, respectively. The results presented suggest that longterm treatment with allopurinol has some therapeutic benefit in CaL especially when administered following treatment with the pentavalent antimonial Glucantime.

Allopurinol↗
PubMed1997

Evaluation and comparison of antibody ELISAs for serodiagnosis of bovine trypanosomosis.

A total of 457 serum samples from cattle kept under moderate tsetse challenge in Mukono County, Uganda, (79 of them with confirmed trypanosomosis) and 86 sera from cattle in Germany were tested for Trypanosoma antibodies using enzyme-linked immunosorbent assay (ELISA) with antigen obtained from blood stream form (BSF) and in vitro cultivated procyclic (PRO) trypanosomes. The BSF and PRO ELISA showed a moderate quantitative correlation. A difference plot revealed a slightly non-linear relation between the two methods. Cut-off values were established using (A) non-exposed controls, (B) exposed negative controls and (C) by mixture distribution analysis of the quantitative ELISA results for the sample from the endemic target population. The diagnostic agreement between both assays was significant (kappa, p < 0.05). The diagnostic accuracy of the two tests relative to standard parasitological detection methods was not markedly different as shown by the areas under the receiver operating characteristic (ROC) plots. In our study, neither non-exposed controls (cut-off A) nor exposed negative controls (cut-off B) were suitable for establishing cut-off values. Based on the cut-off value C, derived from mixture distribution analysis, the proportion of animals with elevated antibody levels in the study population was estimated by both assays at 45% (41-50% binomial 95% confidence interval). This can be regarded as an unbiased estimate of the proportion of 'sero-responders' and not necessarily as a proxy for infection prevalence in the target population. We recommend the PRO ELISA to be used for seroepidemiological surveys, since in vitro cultivation of procyclic trypanosomes allows a continuous and standardised preparation of test antigen.

Animals↗
PubMed1997

The selection of ELISA cut-off points for testing antibody to Newcastle disease by two-graph receiver operating characteristic (TG-ROC) analysis.

Two hundred and sixty field serum samples were tested for Newcastle disease (ND) antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) and the haemagglutination inhibition test (HI). The HI test was regarded as the reference method. Reciprocal titres of 16 and above were considered positive. In this study the two-graph receiver operating characteristic (TG-ROC) analysis was used as a tool for selecting cut-off points. Sensitivity, specificity, efficiency and Youden's index were used as indices of test accuracy. The positive and negative predictive values of the ELISA results were analysed for various prevalence rates.

Animals↗
PubMed1997

Impact of biological factors on the interpretation of bovine trypanosomosis serology.

A total of 457 cattle from dairy farms in Mukono County, Uganda, were investigated for Trypanosoma antibodies by ELISA. The objective of the study was to identify explanatory covariate factors for seropositivity among nine farm-specific and four animal-specific variables. We used logistic regression models for parasitological and serological outcome variables and then compared the adjusted odds ratios for explanatory factors between the models. Age is positively correlated with seropositivity but not with the detection of the parasite. Therefore, age group-specific cut-off values were established using mixture-distribution analysis. This procedure, as well as a mixture-distribution-derived cut-off value for the total sample, resulted in a greater relative efficiency of the ELISA as compared to conventional interpretation (cut-off value defined using non-exposed negative controls). The relevance of age and other biological factors for the serological status is briefly discussed.

Age Factors↗
PubMed1997

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

Acetates↗
PubMed1996

Two-graph receiver operating characteristic (TG-ROC): update version supports optimisation of cut-off values that minimise overall misclassification costs.

TG-ROC was recently introduced as a novel PC-assisted device for cut-off optimisation and evaluation of quantitative serodiagnostic tests (Greiner, 1995, J. Immunol. Methods 185, 145; Greiner et al., 1995, J. Immunol. Methods 185, 123). In this notice a recent extension of the programme is described which facilitates the cut-off selection when estimates of costs associated with false-positive and false-negative results are available.

Cost-Benefit Analysis↗
PubMed1996

Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain.

To study the analgesic efficacy of enadoline, a selective agonist of the kappa-opioid receptor, a double-blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen-codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen-codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.

Acetaminophen↗
PubMed1996

Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain.

Enadoline, a selective agonist of the kappa-opioid receptor, was studied for its analgesic efficacy in patients with pain after obstetric or gynecologic surgery. An initial study involving a comparison of enadoline (2, 5, 15 micrograms), an acetaminophen-codeine (ACET/COD) combination, and placebo showed all treatments to be ineffective analgesics. Therefore, a second study with the same design but using higher doses of enadoline (15 and 25 micrograms) and replacing ACET/COD with morphine 10 mg i.m. was conducted. Enadoline 25 micrograms produced similar pain relief to that of morphine, although of shorter duration, and better than enadoline 15 micrograms or placebo. However, enadoline was associated with dose-limiting neuropsychiatric adverse events, which led to early termination of the study.

Abdomen↗
PubMed1995

Two-graph receiver operating characteristic (TG-ROC): a Microsoft-EXCEL template for the selection of cut-off values in diagnostic tests.

TG-ROC, a template for Microsoft-EXCEL, represents a novel, easy-to-handle approach for selecting cut-off values in quantitative diagnostic tests. In addition to graphical representations of test efficiency, Youden index and likelihood ratios as functions of the preselected cut-off value, the software supports the definition of an intermediate range of test results. For this purpose, two cut-off values are established that realise a pre-selected accuracy level (e.g., 90 or 95% sensitivity and specificity) which can be specified by the user.

Serologic Tests↗
PubMed1995

A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests.

A total number of 50 sera from clinically confirmed cases of canine Borrelia (B.) burgdorferi infection and 44 negative control sera were tested with a B. burgdorferi specific antibody ELISA. The data were submitted to the 'two-graph receiver operating characteristic' (TG-ROC) analysis which is a plot of the test sensitivity (Se) and specificity (Sp) against the threshold (cut-off) value assuming the latter to be an independent variable. Thus, in contrast to the conventional ROC analysis, valid pairs of Se and Sp can be read for pre-assigned threshold values directly from the TG-ROC plots. A cut-off that realises equal test parameters (Se = Sp = theta 0 (theta-zero)) can be obtained as the intersection point of the two graphs. Since the value for theta 0 is below a preselected accuracy level (95% or 90%), two cut-off values are selected that represent the bounds of an 'intermediate range' (IR). IR can be considered as a 'borderline' range for the clinical interpretation of test results. The proportion of the measurement range (MR) that gives unambiguous test results can be expressed using IR as the 'valid range proportion' (VRP = (MR-IR)/MR). VRP and theta 0 are useful parameters for test comparison since they do not depend upon the selection of a single cut-off point. In addition, the selection of cut-off values is supported by graphical displays of efficiency, Youden's index and likelihood ratios which can be considered as functions of the pre-assigned cut-off value. TG-ROC was derived as a user-defined template for a commercially available spreadsheet programme (MS-EXCEL, Microsoft).

Animals↗
PubMed1995

A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder.

This multicenter, double-blind, placebo-controlled, parallel-group, randomized study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary diagnosis of GAD according to DSM-III-R criteria were randomized. The study design included a 1- to 2-week single-blind placebo baseline phase, followed by a 4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for Depression. Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome (IBS) at screening and were evaluated with a gastrointestinal visual analog scale at each visit. Eighty-eight patients were randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial. There was no significant difference in mean change in HAM-A total between placebo (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results. CI-988 did not have an effect on symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia, flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing higher oral doses of CI-988 may be warranted.

Adult↗