Practical approaches to quality assurance of clinical pharmacy programs: a review.
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Biomedical subjects
Publications and source records attributed to C Weber.
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The influence of clinically relevant concentrations of fentanyl, alfentanil, morphine, pethidine, and buprenorphine on polymorphonuclear neutrophilic granulocyte (PMN) adherence was investigated in vitro by using nylon fibre columns. Since none of the drugs produced any significant (p less than 0.05) change of adherence, no evidence of opioid mediated increased risk of postoperative bacterial infection could be found.
The HBsAg carrier state may present as chronic active hepatitis which may proceed to cirrhosis of the liver and to primary liver cell carcinoma. The large scale production of interferons made these substances available for long-term treatment. A deficiency in interferon production in chronic type B hepatitis presented the rational to treat this disease with interferon alpha-A. In this phase II-trial 3/31 patients eliminated HBsAg and 14/31 HBeAg. This was followed by normalisation of liver function tests and probably an improved prognosis. Efficiency of treatment was dependent on the interferon dose, the level of viral replication, the level of liver enzymes before treatment and concurrent infections (e. g. HIV infection). Reactivation occurred in five patients suggesting that the treatment period was too short in some individuals. Future studies will potentially improve efficiency by the modification of the interferon schedule and a better understanding of the mode of action of interferon.
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A multi-centre evaluation of the Behring ELISA Processor II in connection with the Enzygnost-tests from Behringwerke was performed by 3 laboratories following the ECCLS Guidelines for the Evaluation of Analysers in Clinical Chemistry. The performance characteristics were studied with analytical tests for anti-HBs1), HBsAg and anti-CMV2). This evaluation represents, to our knowledge, the first trial in clinical virology with guidelines primarily designed for clinical chemistry. The evaluation revealed that the highly automated Behring ELISA Processor II is a reliable tool in the virological laboratory. The data obtained showed low imprecision and good accuracy. The washing unit proved to be very efficient. No carry-over of reagents was detected in the dispenser system. Several improvements for further developments of the analyser are suggested. This multi-centre study has shown that the ECCLS protocol can be used to evaluate analysers and test systems in clinical virology.
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Two forms of a DNA polymerase have been purified from microplasmodia of Physarum polycephalum by poly(ethyleneimine) precipitation and chromatography on DEAE-Sephacel, phosphocellulose, heparin Sepharose, hydroxyapatite, DNA-agarose, blue-Sepharose. They were separated from DNA polymerase alpha on phosphocellulose and from each other on heparin-Sepharose. Form HS1 enzyme was 30-40% pure and form HS2 enzyme 60% with regard to protein contents of the preparations. Form HS2 enzyme was generated from form HS1 enzyme on prolonged standing of enzyme preparations. The DNA polymerases were obtained as complexes of a 60-kDa protein associated with either a 135-kDa (HS1) or a 110-kDa (HS2) DNA-polymerizing polypeptide in a 1:1 molar stoichiometry. The biochemical function of the 60-kDa protein remained unknown. The complexes tended to dissociate during gradient centrifugation and during partition chromatography as well as during polyacrylamide gradient gel electrophoresis under nondenaturing conditions at high dilutions of samples. Both forms existed in plasmodia extracts, their proportions depending on several factors including those which promoted proteolysis. The DNA polymerases resembled eucaryotic DNA polymerase beta by several criteria and were functionally indistinguishable from each other. It is suggested that lower eucaryotes contain repair DNA polymerases, which are similar to those of eubacteria on a molecular mass basis.
Mononucleated striated muscle cells can be isolated from anthomedusae and cultivated in artificial seawater. In the cultivated muscle the differentiated state is maintained and DNA synthesis is not observed. The isolated striated muscle can be activated by collagenase treatment to transdifferentiate into various new cell types. Between the second and third day following collagenase treatment DNA synthesis is initiated, and mitosis and de novo flagellum formation occur in the isolated muscle. Under these circumstances all isolated striated muscle fragments produce both smooth muscle cells and y-cells (Schmid and Alder, 1984). In experiments, in which either transcription (actinomycin D) or translation (cycloheximide) is inhibited, the activated striated muscle cells do not transdifferentiate but maintain their differentiated state. Inhibition of DNA replication (aphidicolin), however, results in uniform transdifferentiation of striated muscle to smooth muscle cells in the absence of y-cell types (Schmid and Alder, 1984). The fluorescence stain NBD-phallacidin is used to monitor the characteristic change of F-actin pattern of these isolates.
Binding of cytochrome c to cytochrome c oxidase induces a conformational change in both proteins as well as a change of the electronic structure of the heme of cytochrome c, indicating an altered heme c-protein interaction. This follows from the observation that the induced circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of the oxidase-cytochrome c complex in the Soret region differ from the summed spectra of oxidase plus cytochrome c. Spectral changes occur in the complex composed of either the two ferric or the two ferrous hemoproteins. The difference CD and MCD signals saturate at a ratio of 1 heme c per heme aa3. The difference spectra are specific to the cognate complex. The results are interpreted to reflect a direct relationship between the recognition/binding step and the electron-transfer reaction. The conformational rearrangement induced in cytochrome c by cytochrome c oxidase consists of a structural rearrangement of the heme environment and possibly a change of the geometry of the heme iron-methionine-80 sulfur axial bond. This rearrangement may decrease the reorganizational free energy of electron transfer by adjusting the heme c geometry to a state between that of ferri- and ferrocytochrome c.
Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.
Morphological changes occurring in the rabbit retina after fast neutron irradiation levels of 250,500 and 1,000 cGy are discussed. The threshold dose that may cause damage to retinal structures is 250 cGy.
The effects of HOE 760, a highly specific H2-receptor antagonist, on daytime peptone-stimulated and nocturnal gastric acid output were studied (randomized, double-blind crossover) in 10 healthy men. Acid output was monitored at lunch (1200 h to 1400 h) and dinnertime (1800 h to 2000 h) by continuous automatic intragastric titration; from midnight to 0600 h, output was measured by titration of manually aspirated gastric contents. After a 75-mg oral dose (capsule containing HOE 760 granules) at 0800 h peptone-stimulated acid output decreased for at least 12 h. Compared with placebo, significant reductions (p less than 0.05) of 86% and 32% were observed 4-6 h and 10-12 h after drug administration. After another dose of 75 mg at 2100 h nocturnal acid output was significantly reduced (p less than 0.05) by 88%; gastric pH was increased by about 2 units throughout the night. HOE 760 was well tolerated. No adverse reactions occurred; no clinically relevant changes were noted in haematologic, biochemical, urinary, or electrocardiographic variables.
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