BKV replication and cellular immune responses in renal transplant recipients.
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Antigens, Viral↗
Biomedical subjects
A Egli
Publications and source records attributed to A Egli.
[The perspective of global eradication of poliomyelitis].
In recent years, Germany and Switzerland have changed national policies to recommend vaccination with IPV (inactivated polio vaccine) instead of OPV (oral polio vaccine) for protection against poliomyelitis. An all IPV-schedule in routine childhood polio vaccination eliminates the - albeit minimal - risk of OPV-associated paralytic poliomyelitis. However, the impact of such a vaccination scheme on the goal to eventually eradicate poliomyelitis on a global level remains debatable. Published studies indicate that vaccine-derived poliovirus may persist in the environment for prolonged periods of time even after completion of a global eradication programme that relies on the near-exclusive use of OPV in the developing countries. Travellers vaccinated with IPV only might become silently infected with vaccine-derived virus, shedding it in large quantities. We therefore plead for a vaccination schedule that includes at least one last dose of OPV to induce strong mucosal immunity.
Child↗
Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex.
We have developed a technetium labeling technology based on a new organometallic chemistry, which involves simple mixing of the novel reagent, a 99m Tc(I)-carbonyl compound, with a His-tagged recombinant protein. This method obviates the labeling of unpaired engineered cysteines, which frequently create problems in large-scale expression and storage of disulfide-containing proteins. In this study, we labeled antibody single-chain Fv fragments to high specific activities (90 mCi/mg), and the label was very stable to serum and all other challenges tested. The pharmacokinetic characteristics were indistinguishable from iodinated scFv fragments, and thus scFV fragments labeled by the new method will be suitable for biodistribution studies. This novel labeling method should be applicable not only to diagnostic imaging with 99mTc, but also to radioimmunotherapy approaches with 186/188 Re, and its use can be easily extended to almost any recombinant protein or synthetic peptide.
Aldehydes↗
Catabolism of neurotensins. Implications for the design of radiolabeling strategies of peptides.
A major impact in diagnosis and treatment of cancer with peptide based radiopharmaceuticals is expected. Among others neurotensin is considered to be a promising candidate. However, most neurotensin analogues, which bind to the neurotensin receptor have a too short biological half live due to catabolism. Therefore, stabilized fragments have been prepared and labeled with the newly developed [Tc(CO)3](+)-moiety. A single histidine or a (N alpha-His)-Ac group coupled to the N-terminus of the neurotensin fragments were used as a bidentate or a tridentate ligand respectively, which coordinate the metal carbonyl efficiently. Affinity and binding studies of the 99mTc(I) radiolabeled neurotensin fragments revealed a behavior influenced by catabolism and properties of the metal complex.
Affinity Labels↗
Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity.
UNLABELLED: A new peptide labeling method that uses the organometallic aquaion [99mTc(H2O)3(CO)3]+ has been developed. METHODS: A selection of amino acids was labeled at different concentrations with the organometallic aquaion, and the labeling yield was determined by high-performance liquid chromatography. This investigation has shown histidine to be a very potent ligand, with specific activities of up to 6 TBq/micromol (160 Ci/micromol) ligand. Histidine derivatives have been coupled to neurotensin(8-13) (NT[8-13]) and have been labeled with the aquaion, resulting in high specific activities with (N(alpha)-histidinyl)acetic acid-NT(8-13) similar to those with histidine. RESULTS: Histidine derivatives of NT(8-13) labeled using this approach fully retained their receptor affinity, showing KD values of all investigated NT analogs below 1 nmol/L on colon carcinoma HT29 cells. Biodistrbution experiments in BALB/c mice showed complete clearance of (N(alpha)-histidinyl)acetic acid-NT(8-13) from the blood after 24 h and no unwanted accumulation in any tissue. CONCLUSION: The novel labeling method using the organometallic 99mTc-aquaion combines the advantage of highest specific activities with minimal functionalization of proteins and peptides under retention of biologic affinity.
Animals↗
The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients.
Multiple doses of delta 9-tetrahydrocannabinol (THC) capsules (Marinol) and THC hemisuccinate suppositories were administered in 24-hour intervals to 2 patients with organically caused spasticity. After oral doses of 10-15 mg THC, peak plasma levels from 2.1 to 16.9 ng/ml THC and 74.5 to 244.0 ng/ml 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH, major THC metabolite) were measured by GC/MS within 1-8 h and 2-8 h, respectively. After rectal doses of 2.5-5 mg THC, peak plasma levels from 1.1 to 4.1 ng/ml THC and 6.1 to 42.0 ng/ml THC-COOH were measured within 2-8 h and 1-8 h, respectively. The bioavailability resulting from the oral formulation was 45-53% relative to the rectal route of administration, due to a lower absorption and higher first-pass metabolism. The effect of THC on spasticity, rigidity, and pain was estimated by objective neurological tests (Ashworth scale, walking ability) and patient self-rating protocols. Oral and rectal THC reduced at a progressive stage of illness the spasticity, rigidity, and pain, resulting in improved active and passive mobility. The relative effectiveness of the oral vs. the rectal formulation was 25-50%. Physiological and psychological parameters were used to monitor psychotropic and somatic side-effects of THC. No differences in the concentration ability, mood, and function of the cardiovascular system could be observed after administration of THC.
Administration, Oral↗
[Incidence of drug side effects by symptoms and syndromes. From the experiences of the Comprehensive Hospital Drug Monitoring and the Swiss Drug Side Effect Center. As an example: allergic and pseudo-allergic reactions with mild analgesics and NSAID].
From 1974 to 1989, 37,392 patients were admitted to the divisions of general internal medicine of the CHDM hospitals. 19,082 of them were treated with a minor analgesic or an NSAID. In 95 of the exposed patients, an allergic or a pseudoallergic reaction to one or two of these drugs was observed. From 1981 to 1990, general practitioners, hospitals and the pharmaceutical industry reported to SANZ 158 individual cases with comparable reactions to 175 exposures of the same kind. Of the 15 different syndromes and symptoms registered in both institutions, most were reactions of the skin, mainly the usual maculopapular exanthemas (rash), urticaria and angioedema. In the CHDM, allergic or pseudoallergic reactions were observed in 0.23% of patients exposed to minor analgesics (including ASA preparations on a daily dose up to 1.0 g and pyrazolones, mainly metamizole, propyphenazone) and in 0.81% of patients exposed to NSAIDs (including the pyrazolone oxyphenbutazone). In the experience of the Comprehensive Hospital Drug Monitoring in Berne and St. Gallen (CHDM) and the Spontaneous Adverse Drug Reactions Center of Switzerland (SANZ).
Adverse Drug Reaction Reporting Systems↗
Risk factors for adverse drug reactions communication of the CHDM.
In the CHDM (Comprehensive Hospital Drug Monitoring for Adverse Drug Reactions, Bern/St. Gallen), the data of the 34,838 computer registered patient admissions 1974-1988 were available for evaluation. We summarize the results of three different studies: 1. A multivariate analysis of the risk factors to developed an ADR during hospital stay, mainly the number of drugs, age, sex and renal function. 2. The occurrence rate of hyperkalemia under the treatment with diurectics, mainly potassium (K+)-losing with K+ substitution compared to the combination of K(+)-sparing with K(+)-losing preparations. 3. The occurrence-rate of exanthema in relation to amino-penicillin preparations an allopurinol. The results are presented in the communication. (Tab 7, Fig. 1, Ref. 15). Ref. 15.).
Adverse Drug Reaction Reporting Systems↗
Time pattern of allergic reactions to drugs.
Generalized, allergic reactions to drugs show time patterns different from those based on pharmacological concepts. We distinguish three types of reactions: acute reactions (reaction time (RT): 0-60 minutes), subacute reactions (RT: 1-24 hours) and reactions of the latent type (RT: 1 day to several weeks). In this study, allergic reactions in the strict sense are supplemented by reactions considered to be based on intolerance or idiosyncrasy to aspirin, pyrazolones, paracetamol, NSAIDs, quinidine, iodine-containing contrast media and some as yet not understood reactions to local anaesthetics. Out of a total of 23,935 drug monitoring patients with 32,317 hospitalizations in the clinical divisions of internal medicine at three Swiss hospitals during the 1974-1987 period, 951 patients with 1,040 probably or definitely drug-related events of the selected type were recorded. Ultimately, 287 patients with 310 adverse drug reactions (ADRs) fulfilled our selection criteria and were classified into six groups of syndromes (Table 1). (Of the reactions described as maculopapular rash, unspecified rash and special exanthema, only the 159 reactions from the 1985-1987 period out of a total of 889 reactions of this type observed during the whole study period were included in our secondary evaluation.) The total number of 310 reactions (100%) showed the following RT distribution: 36 (11.6%) were of the acute type, 13 (4.2%) of the latent type, 12 (3.9%) could be interpreted as two distinct possible types of reaction to different drugs, and for 3 (1.0%) reactions, the type of reaction was indeterminable. The majority of reactions, 246 (79.4%), were of the subacute type starting within 24 hours of the last drug exposure. Among the 36 reactions of the acute type, 7 events of acute severe dyspnoea were observed which seemed to be as life-threatening as anaphylactic or anaphylactoid shock. These hospital-epidemiological data are of interest for focusing basic research and developing further principles of drug safety.
Anti-Bacterial Agents↗
The late reconstruction of the ligament of the metacarpo-phalangeal joint of the thumb.
The disruption of the ligaments at the level of the MP-joint jeopardizes the function by lack of stability. The reconstruction by free tendon grafting, anchored in a dorso-lateral plane in the metacarpal an in the proximal phalanx, restores stability and good functional results in spite of a slight amount of loss of flexion. Two out of 25 operated thumbs failed and fusion of the MP-joint was necessary. A minimal limitation of flexion may be desirable since a tendon graft never restores a full physiological function. Our data show no need for K-wire transfixation of the MP-joint, since there is no evidence of a difference in late stability with or without such additional fixation. The mean pinch-grip pressure, restored to normal in the majority of cases, was not influenced by the mentioned reduction of flexion nor by the amount of stability restored.
Arthrodesis↗
[Value of intermittent pneumatic compression of the calves for the prevention of postoperative thrombosis of the deep veins].
Six prospective, randomized studies using intermittent pneumatic compression of the calf for prevention of postoperative deep vein thrombosis are available and have been analyzed. In 4 studies a significant reduction in the incidence of deep vein thrombosis could be demonstrated. Compared to controls, the reduction in the deep vein thrombosis rate by intermittent compression is about 60%. The frequency of deep vein thrombosis is lower if the patients are treated not only intraoperatively but also for 24-28 h postoperatively. The difference in deep vein thrombosis rate between these two schedules is statistically probable significant. No definite statement can be made regarding the efficacy of deep vein thrombosis prevention in patients with malignant disease, since here the results are controversial. No studies are available on the effect of intermittent pneumatic compression of the leg on the incidence of fatal postoperative pulmonary emboli. This method must therefore be regarded as an interesting alternative in clinical investigation.
Humans↗
[Surface roughness of dental materials in graphic demonstration].
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Acrylic Resins↗
Derivatives of 1,3,5-triamino-1,3,5-trideoxy-cis-inositol as versatile pentadentate ligands for protein labeling with Re-186/188. prelabeling, biodistribution, and X-ray structural studies.
The pentadentate H3bhci [1,3,5-trideoxy-1, 3-bis((2-hydroxybenzyl)amino)-cis-inositol] and its bifunctionalized analogue H3bhci-glu-H [1,3,5-trideoxy-1, 3-bis((2-hydroxybenzyl)amino)-5-glutaramido-cis-inositol] were synthesized, and their coordination chemistry was investigated with inactive rhenium, with no carrier added Re-188 and with carrier added Re-186. The neutral Re(V) complexes [ReO(bhci)] and [ReO(bhci-glu-H)] are formed in good yields starting from [ReOCl3(P(C6H5)3)2] or in quantitative yield directly from [186/188ReO4]- in aqueous solution by reduction with Sn(II) or Sn(0). The X-ray structures of [ReO(bhci)] and [ReO(bhci-glu-H)] were elucidated revealing pentadentate "side on" coordination of the ligands to the "Re=O" core. The basic cyclohexane frame adopts a chair form in the case of [ReO(bhci)] and a twisted boat form in the case of [ReO(bhci-glu-H)]. [ReO(bhci)] crystallizes in the monoclinic space group C2/c with a = 27.425(3), b = 14.185(1), c = 19.047(2) A, and beta = 103.64(2) degrees and [ReO(bhci-glu-H)] in the monoclinic space group P21/c with a = 13.056(3), b = 10.180(1), c = 22.378(5) A, and beta = 98.205(9) degrees. Both 188Re complexes are stable in human serum for at least 3 days without decomposition. After injection into mice, [ReO(bhci-glu)]- is readily excreted through the intestines, while [ReO(bhci)] is excreted by intestines, liver, and the kidneys. TLC investigations of the urine showed exclusively the complexes [ReO(bhci-glu-H)] and [ReO(bhci)], respectively, and no decomposition products. For derivatization of antibodies, the carboxylic group of [ReO(bhci-glu-H)] was activated with N-hydroxysuccinimide, which required unusually vigorous reaction conditions (heating). The anti colon cancer antibody mAb-35 [IgG and F(ab')2 fragment] was labeled with [186/188ReO(bhci-glu)] to a specific activity of up to 1.5 mCi/mg (55 MBq/mg) with full retention of immunoreactivity. Labeling yields followed pseudo-first-order kinetics in antibody concentration with the ratio of rates between aminolysis and hydrolysis being about 2. Biodistributions of 186Re-labeled intact mAb-35 as well as of its F(ab')2 fragment in tumor-bearing nude mice revealed good uptake by the tumor with only low accumulation of radioactivity in normal tissue.
Animals↗