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Biomedical subjects

E Deutsch

Publications and source records attributed to E Deutsch.

At least 109 records · Page 6Linked to original sources

Quantitative determination of human protein C. Evaluation of a "fast" functional assay in comparison to a "traditional" functional and an immunological assay.

A fast functional assay for protein C was evaluated and compared with a traditional functional and an enzyme linked immunosorbent assay in parallel for the same plasma samples derived from 43 healthy subjects, 12 patients with severe hepatic dysfunction, and 23 patients under stable oral anticoagulation. By all three test systems significantly lower levels of protein C were obtained in both groups of patients compared with normal subjects (p less than 0.0001). No significant between - assay differences were found in normal subjects and in patients with hepatic dysfunction; by correlation analysis coefficients higher than 0.8 were calculated between the measurements of the three tests. In patients under stable oral anticoagulation, however, the immunologic test yielded higher values than the traditional (p less than 0.05) and, more pronounced, the fast functional assay (p less than 0.0001); no or only borderline significant correlations between the results were found. In these patients protein C levels measured with the traditional functional assay were in the same range as the activity levels of factors II, VII, IX, and X, whereas the fast functional test yielded significantly lower levels. The presented results indicate that very similar protein C levels were obtained with both functional and the immunologic assay except in patients under oral anticoagulation.

Adult↗

Quantitative HPLC determination of [99mTc]-pertechnetate in radiopharmaceuticals and biological samples--I. Technique development.

Techniques have been developed which allow HPLC (high performance liquid chromatography) to be used for the quantitative determination of [99mTc]pertechnetate in radiopharmaceuticals and biological samples. An instrumental technique accounts for 99mTc species which do not elute from the HPLC column, while a chemical technique obviates interferences caused by Sn(II). These two techniques are incorporated into an anion exchange HPLC procedure which is applied to the determination of [99mTc]pertechnetate in 99mTc-diphosphonate radiopharmaceuticals and biological samples.

Calibration↗

Exercise training for competitive tennis.

This article reviews the muscle physiology underlying various forms of activity, as well as the adaptive responses induced by specific forms of training, and thus provides a rational basis for the design of a training program for competitive tennis.

Exercise Test↗

Neutral technetium(II)-99m complexes as potential brain perfusion imaging agents.

A series of eight neutral technetium(II)-99m complexes of general formula tr-[99mTcIID2X2]0, where D represents a chelating ditertary phosphine or arsine ligand and X represents a halide or pseudohalide ligand, has been prepared and characterized by HPLC comparisons to the known 99Tc analogs. Several members of this series exhibit significant brain uptake in rats, with maximum uptake (1.2% dose/brain at 1 min after injection) being exhibited by tr-[99mTcII (DIARS)2Cl2]0 where DIARS represents o-phenylenebis(dimethylarsine). Surprisingly, several cationic Tc(III) analogs, tr-[99mTcD2X2]+, also exhibit significant brain uptake, presumably via a mechanism which involves in vivo reduction to the neutral Tc(II) form. The complicated interrelationships among the chemical and biological properties of the tr-[99mTcIII/IID2X2]+/0 couples, and the dependencies of these properties on the nature of D and X, provide possible means by which this class of complexes might be manipulated to yield an effective 99mTc brain perfusion imaging agent.

Animals↗

Identification of a defective factor XI cross-reacting material in a factor XI-deficient patient.

A homozygous factor XI-deficient girl, who appeared to be positive for cross-reacting material (CRM+) was studied for clarification. Factor XI antigen (F XI:Ag) was measured by radial immunodiffusion using monospecific, heterologous anti-factor XI antibodies. Factor XI coagulant activity (F XI:C) was determined in a modified activated partial thromboplastin time (APTT) test. The ratio of F XI:C to F XI:Ag was 0.04 for the proposita, as compared with 0.7 to 0.74 in the other family members. In contrast, 12 normal individuals had ratios of F XI:C to F XI:Ag of 1.04 +/- 0.15. F XI esterolytic activity was clearly higher than F XI:C in the proband, but not in her relatives. Immunoblotting studies demonstrated F XI CRM in the patient's plasma. Chromatography on diethylaminoethanol (DEAE)-Sephadex at pH 8.4 led to an almost complete removal of F XI from the plasma. The defective F XI was not bound to a negatively charged kaolin surface due to an abnormal interaction with high-mol-wt kininogen (HMWK).

Antigens↗

In vivo inorganic chemistry of technetium cations.

Technetium-99m cations are of interest because of their potential use as myocardial perfusion imaging agents. These species can undergo in vivo reactions which markedly affect their biodistribution patterns. Four such cases of reactions are presented and discussed: (1) simple ligand substitution; (2) metal centered redox processes; (3) reactions of coordinated ligands; (4) outer sphere association reactions. New experimental techniques appropriate for investigating these reactions at the 10(-10) M concentration level of technetium encountered in vivo are also presented and discussed. The latter three classes of reactions are illustrated by examples taken from the recent literature and from unpublished data.

Animals↗

Development of nonreducible technetium-99m(III) cations as myocardial perfusion imaging agents: initial experience in humans.

A series of 15 nonreducible technetium-99m(III) complexes of formula tr-[99mTcL(Y)2]+ has been prepared by a general synthetic route based on reductive addition of Y to the technetium-99m (99mTc) intermediate [99mTcL(O)]+. In these complexes, selected for potential use as myocardial imaging agents, L represents one of the two tetradentate Schiff base ligands N,N'-ethylenebis(acetylacetone iminato), (en), or N,N'-propylene-1,2-bis(acetylacetone iminato), (pn), while Y represents a monodentate phosphine, phosphite or isonitrile ligand as exemplified by P(CH3)3, P(OCH3)3 and CN-C(CH3)3. Of these 15 complexes, several with octanol/saline partition coefficients in the range 0.04-20 exhibit significant myocardial uptake in rats and dogs. Of these, none exhibit detectable myocardial washout, providing strong support for the hypothesis that myocardial washout occurs only for those 99mTc(III) cations that undergo in vivo reduction to the neutral 99mTc(II) form. Evaluation of the prototypical complex tr-[99mTc(en)(P(CH3)3)2]+ in seven normal volunteers and patients establishes that it is only a mediocre myocardial imaging agent in man.

Animals↗

Characterization of technetium radiopharmaceuticals by thin-layer spectroelectrochemistry.

Optically transparent thin-layer electrode (OTTLE) techniques have been used to characterize technetium complexes of biomedical importance. Different Tc oxidation states have been generated at the electrodes and absorption spectra determined. Small cell volumes allow the study of materials available in small quantities, and a flow cell configuration has also been used. Heart and bone imaging agents have been studied.

Journal Article↗

HPLC separated fractions of 99mTc(NaBH4)-HEDP as myocardial infarct imaging agents.

Component fractions of 99mTc(NaBH4)-HEDP mixtures, isolated by anion exchange high performance liquid chromatography (HPLC), have been evaluated as myocardial infarct imaging agents in two animal models. Results from both the isoproterenol-induced myocardial infarction model, and the heat-induced myocardial necrosis model, show that the several HPLC isolated components exhibit significantly different abnormal/normal heart uptake ratios. In addition, the HPLC isolated component of shortest chromatographic retention time exhibits a higher abnormal/normal heart uptake ratio than does 99mTc(Sn)-PyP, the current agent of choice for clinical myocardial infarct imaging.

Animals↗

The effect of formulation conditions on the distribution of 99mTc(NaBH4)-HEDP components separated by anion exchange HPLC.

Reduction of 99mTcO4- by NaBH4 in the presence of HEDP leads to a mixture of 99mTc-containing complexes which can be separated by anion exchange high performance liquid chromatography (HPLC). The distribution of complexes within this mixture can be varied by controlling pH, the concentration of HEDP, the concentration of technetium, and the presence of air. Suitable control of these formulation conditions can yield mixtures which consist of essentially (greater than 85%) one component. Arguments are presented to support the view that the components of 99mTc(NaBH4)-HEDP and 99mTc(NaBH4)-MDP mixtures are in fact oligomeric or polymeric complexes that can contain technetium centers in at least two different oxidation states.

Bone and Bones↗

The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine.

The beta emitting isotopes 186Re and 188Re are logical choices on which to base therapeutic radiopharmaceuticals that might be expected to be analogous to diagnostic radiopharmaceuticals based on 99mTc. However, the chemistry of rhenium is sufficiently different from that of technetium so that the development of Re radiopharmaceuticals often cannot be predicated on the known chemistry and biological behavior of 99mTc radiopharmaceuticals. The relevant chemical differences involve the greater stability of the higher oxidation states of Re (and thus the greater tendency of reduced Re radiopharmaceuticals to undergo re-oxidation to perrhenate), and the greater substitution inertness of reduced Re complexes. These differences are illustrated in the preparation and use of 186Re (Sn)-HEDP and 99mTc(Sn)-HEDP diphosphonate radiopharmaceuticals designed, respectively, for palliative therapy and diagnosis of metastatic cancer to bone, and in the preparation and biodistribution of tr[186Re(DMPE)2Cl2]+ and [186Re(DMPE)3]+, analogs to the potential myocardial perfusion imaging agents tr-[99mTc(DMPE)2Cl2]+ and [99mTc(DMPE)3]+. [HEDP = (1-hydroxyethylidene)diphosphonate; DMPE = 1,2-bis(dimethylphosphino)ethane].

Animals↗

Differing attitudes of industry and academia towards controlled clinical trials.

A consensus conference was held in 1984 on controversial issues concerning controlled clinical trials. Thirty-six individuals working in academic institutions, forty-six in industry and twelve in regulatory authorities participated. Academics accepted and industrial representatives rejected the following: existing regulations cannot cope with the rate at which new treatments develop; drug companies may be reluctant to undertake surveillance programmes because sales will fall if adverse reactions are detected; novel remedies should not be promoted before extensive post-marketing surveillance; third parties should finance trials promising to reduce the costs of illness and trialists should be separated from sponsors in data analysis and interpretation, the investigator owning the data unless stated otherwise. Industrial representatives supported and academics rejected the following: government price control inhibits drug development and a multicentre trial can be justified simply by the wish to speed drug registration.

Attitude↗

Effect of thyroid hormones on plasma protein concentrations in man.

Plasma concentrations of proteins secreted by the liver (prealbumin, haptoglobin, transferrin, ceruloplasmin, alpha 1-antitrypsin, antithrombin III, and T4-binding globulin) and proteins mainly derived from endothelium [fibronectin, angiotensin-converting enzyme (ACE), and factor VIII-related antigen (F VIII R:Ag)] were measured in 27 hyperthyroid and 30 normal women. Significantly increased plasma concentrations (P less than 0.01) of endothelium-associated proteins, including fibronectin, ACE, and F VIII R:Ag, were found in hyperthyroid patients, while levels of proteins of primarily hepatic origin were normal. To determine whether the increase in endothelium-associated proteins in hyperthyroidism was directly related to elevated thyroid hormone levels, seven normal women were given T3 (25 micrograms, three times daily) for 2 weeks. These women had a consistent rise (P less than 0.05) in plasma concentrations of fibronectin, ACE, F VIII R:Ag, and tissue plasminogen activator. The rise in endothelium-associated proteins persisted for 10 days after cessation of T3. Plasma concentrations of hepatically synthesized proteins did not change. We conclude that thyroid hormone action either promotes endothelial protein synthesis or impairs its clearance.

Adolescent↗

[Comparative pharmacokinetics of the beta-1 receptor blookader celiprolol after a single oral administration in subjects with health kidneys and in patients with impaired renal function].

Pharmacokinetic parameters were determined after the oral administration of a single tablet containing 200 mg celiprolol HCl to 8 healthy volunteers with normal kidney function and 6 patients with stable impaired renal function of different degrees of severity. The plasma levels and the urinary excretion of celiprolol were followed up for 48 hours after administration with the help of specific chemo-analytical methods. The substance was equally well absorbed both by healthy volunteers and patients with renal disease. While the cumulative renal excretion (0 to 48 hours after administration) was reduced from 18.2% in healthy volunteers to 2.3% of the applied dose in kidney patients, the global elimination constant k fell from 0.104 h-1 in healthy volunteers to 0.072 h-1 in the patients with renal disease. It can be assumed that in patients with impaired renal function at least a part of the lacking renal elimination of celiprolol can be taken over by "extrarenal elimination". According to the method of Dettli a reduction in dosage of the beta 1-blocker, celiprolol is not necessary in patients with more or less impaired kidney function.

Administration, Oral↗

Clotting activities and antigen concentrations of contact factors in kidney disease.

Factor XII, prekallikrein (PK) and high molecular weight kininogen (HMWK) clotting activities and antigen concentrations in kidney disease patients were studied. Chronic hemodialysis led to a reduction of F XII, PK and HMWK clotting activities. F XII and PK antigen levels were also low. In contrast, the HMWK antigen was normal with respect to concentration as well as electrophoretic migration behaviour on 2 D-immunelectrophoresis. In kidney transplant recipients more than three month after the transplantation, we found an increased of F XII and PK clotting activities, which appeared to depend on the time elapsed since the operation. However, the antigen levels remained normal. The group of chronic kidney disease patients not requiring hemodialysis exhibited normal mean values of all three clotting activities as well as normal F XII and HMWK antigen levels. The PK antigen was reduced. However, a separate evaluation of F XII clotting activities (F XII:C) in patients with glomerular nephritis showed elevated F XII:C which correlated with the BUN values. During acute processes of the kidney disease we observed very high PK clotting activities, which normalized with stabilization of the patients. Our results show that the contact phase coagulation factors behave abnormally in certain kidney disease patients.

Blood Coagulation↗