[Economics of nursing, a field in itself].
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Biomedical subjects
Publications and source records attributed to G Thiele.
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We have developed a protocol for rapid sequencing of short DNA stretches (15-20 nt) using MALDI-TOF-MS. The protocol is based on the Sanger concept with the modification that double-stranded template DNA is used and all four sequencing reactions are performed in one reaction vial. The sequencing products are separated and detected by MALDI-TOF-MS and the sequence is determined by comparing measured molecular mass differences to expected values. The protocol is optimized for low costs and broad applicability. One reaction typically includes 300 fmol template, 10 pmol primer and 200 pmol each nucleotide monomer. Neither the primer nor any of the nucleotide monomers are labeled. Solid phase purification, concentration and mass spectrometric sample preparation of the sequencing products are accomplished in a few minutes and parallel processing of 96 samples is possible. The mass spectrometric analyses and subsequent sequence read-out require only a few seconds per template.
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The clinical value of amylase and lipase measurement for the diagnosis of acute pancreatitis was evaluated in 253 patients presenting with acute abdominal pain. Acute pancreatitis was detected in 32 patients by computed tomography or ultrasound. In the serum samples collected on days 0-1 after the onset of symptoms, lipase was elevated in 100% and amylase in 95%. A 95% sensitivity/specificity was reached at a lipase cutoff near twofold above normal. The receiver-operating characteristics (ROC) showed similar curves for both enzymes, lipase being slightly superior to amylase. The ROC curves from days 2-3 demonstrated a much lower sensitivity/specificity of both enzymes. Lipase, however, was notably superior to amylase: at a sensitivity of 85% the specificity of lipase (amylase) was 82% (68%). In samples from days 4-5 the accuracy of the enzyme assays was even worse; at a sensitivity of 60% the specificity did not increase above 70%. The diagnostic value of simultaneous measurement of amylase and lipase was tested at different cutoffs in two groups: the OR group, in which one of the two parameters had to be elevated, and the AND group, in which both parameters had to be above normal. Combination of both parameters mainly improved the specificity of the assay (from 91 to 98% on days 2-3 and from 93 to 97% on day 4-5) but only when, in the OR group, twofold elevated amylase was combined with lipase. We conclude that the simultaneous determination of serum lipase and amylase marginally improved the diagnosis of acute pancreatitis in patients with acute abdominal pain, however, the sensitivity of the assay with samples collected 4-5 days after onset of the disease remained low.
OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.
During spaceflights, astronauts are exposed to many stressors (e.g., microgravity, confinement) that may impair human information-processing capabilities. In order to analyze the possible effects of the space environment on human time-sharing efficiency, a single-case experiment was conducted in which the time course of dual-task performance (unstable tracking with concurrent memory search) of one space crew member was monitored repeatedly (13 times) throughout an 8-day space mission. Tasks were taken from the Advisory Group for Aerospace Research and Development battery of Standardized Tests for Research with Environmental Stressors. Comparisons of in-flight, preflight, and postflight performance revealed no decrements in single-task memory search performance but did reveal clear impairments in single-task tracking and dual-task performance. From these results we conclude that psychomotor processes and higher attentional functions are particularly prone to disturbance effects in space.
Selected immunomodulatory effects of levamisole were studied in patients with asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice treated with methyl-azoxymethanol acetate) for colon tumors. In the patient population studied, there was no augmentation of cellular cytotoxicity or alteration in lymphocyte subpopulations that participate in these functions. An increase in Fc receptor binding on circulating monocytes was apparent at the 4-week timepoint; however, a corresponding increase in antibody-dependent cellular cytotoxicity was observed in only one of the six patients studied. In most patients, cellular cytotoxicity diminished with time. No significant effects on cellular immunity or carcinogenesis were observed in our murine studies. However, treatment with levamisole did increase circulating immunoglobulin levels and IgM response in mice immunized with the T-dependent antigen keyhole limpet hemocyanin. This parameter was not tested in the human trial. Failure to demonstrate antitumor effects on cellular immunity by levamisole in both human and murine studies suggests that these effects, if they do exist, may involve immunological parameters that were not tested using our methods or that may not be apparent in patients with more advanced malignancy.
The penetration of 14C-labelled alcohols (methanol, ethanol, n-butanol), 14C-labelled carbonic acids (formic, acidic, propionic, valerianic, octanoic, malonic, succinic and lactic acid), 14C-drugs (procain, barbital), and 14C-sugars (saccharose, xylose) into about 800 human deciduous or permanent teeth, both healthy and carious, was investigated. Dental enamel up to the cemento-enamel junction was incubated at a pH-value of 5.0 or 6.8 for 1 or 24 hours. For measurement of radioactivity, the dentine of the root was obtained by trepanation. Between intact and carious permanent teeth only slight differences were observed in case of the diffusion of methanol and ethanol (2% of the incubation medium), while n-butanol penetrated the dentine to an extent of 4.2% at a pH of 5.0. The monocarbonic acids penetrated the enamel of healthy teeth within 24 hours to an extent of 6.6-19.2% of the content of the incubation medium, while the dicarbonic (succinic and malonic) acids reached amounts of 3.6 and 9.2%, and the percentage of lactid acid which penetrated the enamel reached 2.9%, respectively. Under all conditions tested, saccharose penetration was higher in carious than in healthy teeth (3.8 vs 6.5%). The highest uptake was found in experiments with barbital; it was more pronounced in deciduous than permanent teeth (16.2 vs 12.4%). The data could be of interest in the therapy of inflammatory and other processes of the pulp.
Living in the space environment and exposure to microgravity induce a number of effects that may interfere with human cognitive and psychomotor performance. However, up to now very few attempts have been made to monitor possible impairments of human performance during space missions. In the present single-case study several cognitive and psychomotor functions were monitored during an 8-day space mission to an orbital station using a computerized performance monitoring device. This device included four different tasks, which were selected from a battery of Standardized Tests for Research with Environmental Stressors published recently by the NATO Advisory Group for Aerospace Research and Development, and which demanded logical reasoning and decision-making functions, memory retrieval functions, and fine manual control. Each task was performed 23 times (6 preflight, 13 inflight, 4 postflight sessions). By means of single-subject statistics inflight performance was compared with baseline performance during pre- and postflight sessions. In accordance with the few previous performance studies conducted during space flights, speed and accuracy of short-term memory retrieval and logical reasoning functions remained unimpaired during the stay in space. However, clear decrements in tracking performance were found, showing to increased difficulties in fine manual control. These results suggest that performance decrements in space may arise primarily in psychomotor functions due to alterations requiring an effortful accommodation of motor skills which had been acquired under 1-g conditions to the new conditions of microgravity.
On the basis of 10 patients with chronic cor pulmonale due to chronic obstructive lung disease and secondary polyglobulia in a clinical and experimental study could be made evident that by limited isovolaemic haemodilution (haematocrit value of 0.58 +/- 0.03 reduced to 0.36 +/- 0.01) are to be expected a decrease of the total pulmonary-arterial resistance, a reduction of the mean pulmonary arterial pressure, an increase of the partial O2-pressure as well as an increase of the heart index. Analogically to this as a consequence of the improved rheologic conditions a clear involution of the clinical signs of a heart insufficiency developed. Complications were not observed. The technique of the limited haemodilution should find a broader use in the medical practice, taking into consideration the isovolaemia as adjuvant treatment principle for patients with the indication mentioned.
The isolation and characterization of human herpesvirus-6 (HHV-6) has been hindered by the lack of cell lines useful for its rapid propagation. Recently, we have reported that the MRC-5 cell line (human diploid lung fibroblasts) was susceptible for HHV-6 infection. In this study, we report on the isolation of HHV-6 from the peripheral blood or buffy coat of three chronic fatigue syndrome patients, one post-liver transplant patient, and one severe chronic active Epstein-Barr virus syndrome patient using the MRC-5 cell line. Additionally, it was observed by Southern blot hybridization studies that four of five isolates had different restriction enzyme fragment patterns than the isolate obtained from the National Institutes of Health with Eco RI. These data suggest the usefulness of the MRC-5 cell line in the isolation and characterization of HHV-6 from various patients.
Details for design and construction of template blocks for the increased sensitivity of radial immunodiffusion (RID) assays are described. The sensitivity of the template RID was 10-fold higher for quantifying albumin and 5-fold higher for IgG than the conventional RID with wells cut into the agarose. The system described in this communication resulted from the unit which provided the most consistent results from a variety of trials with different block thicknesses, chamber sizes and depths, and chamber arrangements.
Single neuronal units from the pineal stalk and the pineal body of hamsters, guinea pigs and rats were recorded during photic stimulation of the lateral eyes in order to identify the retinal photoreceptor that mediates the environmental control of the mammalian pineal. Two cell types could be distinguished: one type was characterized by spontaneous spike discharges that were irresponsive to light stimulation of the eyes and the pineal body; the other, also spontaneously active, responded to flash stimulation of the lateral eye with On- and Off-discharges. With increasing light intensity, the spike frequency of the second response type followed a sigmoidal function up to a saturation level. Spectral sensitivity curves of all dark-adapted animals peaked at 500 nm. During light adaptation (18 microW/cm2) action spectra exhibited an additional maximum in the red (560 nm, rats and hamsters) and in the blue (450 nm, guinea pigs) light, respectively. Chromatic adaptation to orange light diminished the sensitivity at longer wavelengths, whereas adaptation to blue-green light enhanced the sensitivities at longer wavelengths. Thus, the spectral sensitivity recorded from pineal units of hamsters, guinea pigs and rats corresponds to those described for retinal ganglion cells, which indicates that both rods and cones contribute to the light-sensitivity of the mammalian pineal gland. Direct illumination of the pineal gland did not influence the activity of pineal units.
An enzyme-linked immunosorbent assay (ELISA) was used to measure IgG antibody titers against a synthetic peptide whose sequence was derived from the glycine-alanine repeating region of Epstein-Barr virus nuclear associated antigen 1 (EBNA-1). Antibody titers were determined in sera from 15 normal subjects, sera from 21 normal male siblings of X-linked lymphoproliferative syndrome (XLP) patients, from 20 XLP patients comprising a total of 42 samples, and ten samples before and ten samples after gamma-globulin therapy in ten patients with XLP. Data analysis demonstrated that while there are differences between the ELISA and ACIF, they appear to measure a similar response as demonstrated by their correlation coefficient (0.77) and the GMT to EBNA observed by both methods. No cross-reactivity of cytomegalovirus antibodies to the EBNA-1 peptide was observed by immunoblotting, ELISA or ACIF using adsorption against AD-169 infected MRC-5 cells. However, non-specific binding was observed if samples were not pre-incubated in a 10% goat serum PBS-Tween 20 solution. This pre-treatment removed the non-specific binding that falsely elevated the GMT in approximately 15% of both normal and XLP samples in ELISA. The ELISA system appears to be a sensitive, reproducible and objective test that may be useful for assessing the antibody response of patients to the EBNA-1 protein.
On the basis of a retrospective study the importance of the haematological parameter MCV (mean corpuscular volume) for the recognition of chronic alcohol addicts was investigated. It was shown that in males a macrocytosis of the erythrocytes (MCV greater than or equal to 100 fl) refers to a daily alcohol abuse of more than 80 to 100 g, when diseases disturbing the blood formation and medicamentous injuries have been excluded. The sensitivity of this haematological screening method lies in the same order of magnitude as the sensitivity in the determination of the gamma-glutamyl transpeptidase. The daily abuse of high per cent spirits seems to have a larger effect on the development of a macrocytosis than the daily abuse of equivalent quantities of beer.
In order to classify the different cell types involved in signal transmission of the photoreceptive pineal organ of the goldfish, Carassius auratus, intra- and extracellular electrical responses were recorded from photoreceptors and second-order neurons. Photoreceptor responses to light consisted of hyperpolarizing potentials up to 30 mV. The responses were graded with intensity and their voltage-intensity relation followed the hyperbolic function V/Vmax = In/In + sigma n. Latencies varied between 500 msec for responses near threshold and 60 msec for supersaturating flashes. The response duration increased up to 60 sec for flashes 2 log units above the saturation level. Action spectra of individual photoreceptors peaked at lambda max = 530 nm and corresponded to measurements of extracellular slow mass potentials or spike potentials. Slow mass potentials exhibited similar characteristics as intracellular recorded photoreceptor potentials with respect to latency, voltage-intensity curves and spectral sensitivity. Ganglion cells showed maintained discharges under conditions of steady illumination. The discharge rate changed inversely with the logarithm of steady illumination over a range of 8 log units. The response to light flashes was purely achromatic and consisted of inhibition of the maintained discharge. The physiological properties demonstrate that the pineal organ of the goldfish is an effective functional photoreceptor organ operating both in dim and in bright light. The light-induced hyperpolarization of photoreceptors lead to an inhibition of the nervous discharge of ganglion cells. The direct flow of information from photoreceptors to ganglion cells is the basic channel of data processing in the goldfish pineal.
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Using a continuous traction method we succeeded in extracting 24 bacterially contaminated and fixed in the heart electrodensounds around 4 years after pacemaker implantation without complications worth mentioning in 7.5 days (1-27). The tissue attached to 20 sound points contained 9 times portions of the myocardium, 9 times remainders of the endocardium, 12 times particles of the connective tissue and 17 times suppurative inflammatory tissue. After extraction of the sound and aimed chemotherapy in all 24 patients the inflammatory pathological conditions rapidly and free from recidivations receded.