Criminal liability of physicians and other health care professionals in Hungary (review of case law between 1996-2000).

The authors examine the criminal cases involving physicians and other health care workers between January 1996 and December 2000 inclusive. in Hungary. The data are based on the registry of the Criminal Prosecutor's Office. Altogether 94 cases were initiated in this period of time, the accused of the criminal proceeding was a registered nurse in 9 cases, an ambulance paramedic in 5 cases, a pharmacist in 3, and a physician in 77 cases. In cases where registered nurses were involved, the most common act was negligent change of medication or providing inadequate custody of a patient in need, pharmacists were also accused for negligent change of medicinal products. In case of ambulance assistants the most common violation of the professional rules was diagnostic failure or not responding to the call in time. As to physicians, mostly primary care physicians were accused (29%), usually for failing to examine the patient or for diagnostic error, obstetricians-gynecologists (17 %) and traumatologists (12 %) were also frequently accused.

Density functional study of infinite polyserine chains.

Two different helical conformations (alpha and 3-10 helices) of polyserine are studied using density functional theory. The infinite system characterized by exact translational-rotational symmetry is examined in vacuum using the BLYP exchange-correlation functional. Geometry analysis in terms of hydrogen bond strength and total energies of the different conformers are presented. The structural changes due to the presence of the serine side chain are identified comparing the polyserine and polyglycine chains. The rotational energy curves of the side chain are presented for both investigated helices. Band structures of polyserine and polyglycine conformers are also compared.

Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models.

Three models, linked in series, can be used to analyze combined pharmacokinetic (PK) and pharmacodynamic (PD) data arising from non--steady-state experiments. A PK model relates dose to plasma drug concentration (Cp); a link model relates Cp to drug concentration at the effect site (Ce); and a PD model relates Ce to drug effect (E). All three submodels can be stated parametrically. Recently the use of a nonparametric PD submodel has been proposed (CLIN PHARMACOL THER 1984;35:733-41). In this article we use an extended nonparametric approach that represents both the PK and PD models nonparametrically, but retains a parametric link model. Cp data from several PK models and E data from several PD models were simulated. After the addition of noise to both the Cp and E data, they were analyzed by both the parametric and extended nonparametric methods. The methods were compared by how well they estimated the PD model. To assess robustness, the effect of misspecification of the PK submodel on the goodness of estimation of both methods was also compared. In the absence of model misspecification, the parametric method usually estimates the PD model better than the nonparametric method. However, this difference in the performances diminishes and even reverses when the PK model is misspecified. Because one can rarely be certain that model misspecification is absent, the nonparametric approach may offer a distinct advantage for routine analysis of PK/PD data.

Kinetic pathways of formation and dissociation of the glycerol-3-phosphate dehydrogenase-fructose-1,6-bisphosphate aldolase complex.

Quantitative analysis of the time courses of fluorescence anisotropy changes due to the binding of fructose-1,6-bisphosphate aldolase to the dissociable cytoplasmic glycerol-3-phosphate dehydrogenase covalently labelled with fluorescent dye was carried out. The behaviour of the aldolase-dehydrogenase system seems to be consistent with a cyclic reversible model characterized by the formation and dissociation of complexes of both the monomeric and the dimeric forms of dehydrogenase with aldolase, and rapid equilibrium between the free monomeric and dimeric forms of dehydrogenase. The half-life time of the formation of dimeric dehydrogenase-aldolase complex at the concentration of the enzymes expected to exist in the cell (i.e. in the micromolar range) is some minutes, and the time needed for equilibration between the aldolase-bound dimeric and monomeric forms of dehydrogenase is a few minutes as well. Consequently, one may expect that both the formation and the dissociation of this heterologous enzyme complex have physiological relevance.

Change in the reactivity of the active-site serine OH of butyrylcholinesterase caused by a new reversible inhibitor.

The 2-chloro-12-(2-piperidinoethyl)-dibenzo[d,g] (1,3,6)-dioxazocine . HCl (EGYT-2347), a new specific inhibitor of butyrylcholinesterase inhibits reversibly and non-competitively the enzymatic hydrolysis of butyrylthiocholine iodide (Ki = 0.15 microM, at 37 degrees C in 0.1 M Tris/HCl, pH 7.5). The theoretical progress curve of product accumulation has been developed for the case when a non-competitive reversible inhibitor (EGYT-2347) and an active-site-directed irreversible inhibitor (diisopropylfluorophosphate) act simultaneously. By the aid of this approach it was concluded that the butyrylcholinesterase--EGYT-2347 binary complex does not react with diisopropylfluorophosphate either because of a structural change caused by binding or by the direct steric hindrance of EGYT-2347.

Localization of glyceraldehyde-3-phosphate dehydrogenase in intact human erythrocytes. Evaluation of membrane adherence is autoradiographs at low grain density.

Human erythrocytes were treated with highly tritiated [3H]iodoacetate under conditions when half of the label became attached to glyceraldehyde-3-phosphate dehydrogenase. After fixation, the cells were subjected to electron microscopic autoradiography. For the evaluation of distribution of grains, which were relatively few, a computerized method was developed. Statistical analysis of data showed the significant adherence of grains to the cell membrane. The results support the view that glyceraldehyde-3-phosphate dehydrogenase is localized near the membrane in the intact erythrocyte.

Crosslinking with bifunctional reagents as a means for studying the symmetry of oligomeric proteins.

A method based upon the principle that unlike domains of bonding are reflected in different reactivities and distribution of residues that can be crosslinked, has been elaborated for the determination of symmetry of oligomeric proteins. The derivation of theoretical curves for the prediction of crosslinking patterns of tetramers produced by reaction with a bifunctional reagent and subsequent sodium-dodecylsulphage-gel electrophoretic analysis, is presented. Based upon the theory the symmetry properties of a tetramer, to the extent whether it is an isologous or heterologous association, can be deduced by a simple calculation. Crosslinking patterns obtained with rabbit muscle aldolase and pig muscle lactate dehydrogenase after treatment with a series of diimidoesters of increasing chain length are evaluated and shown to be consistent with the expectations for isologous tetramers. From the patterns obtained with the various reagents the distances between lysyl residues located nearest to each other in different subunits in the two proteins could also be determined.

Effect of modification of SH-groups in D-glyceraldehyde-3-phosphate dehydrogenase on the properties of enzyme--coenzyme complex.

The NAD-binding of pig muscle glyceraldehyde-3-phosphate dehydrogenase after modifying certain SH-groups of the enzyme was studied by spectrophotometric titration and gel-chromatography. The enzyme modified on residue Cys-149 with N-ethylmaleimide, iodoacetate or p-mercuribenzoate binds NAD less tightly than does the unmodified enzyme. However, the differences between the NAD-binding sites characteristic of the native tetrameric enzyme are largely retained in the modified enzyme. Residue Cys-153 is near to the surface of the enzyme and is temporarily exposed due to the fluctuation of the protein. It can be modified only after blocking Cys-149. Modification of residue Cys-153 with N-ethylmaleimide does not further influence NAD-binding. Reaction of Cys-153 with p-mercuribenzoate does not directly cause the release of NAD. In this case the enzyme-coenzyme complex decomposes due to secondary conformational changes. This followed from the finding that the disappearance of the absorption band characteristic of the enzyme-coenzyme charge transfer complex is a first order process is equal to that of the structural changes following mercaptide formation of Cys-153.