Different potencies of dihydropyridine derivatives in blocking T-type but not L-type Ca2+ channels in neuroblastoma-glioma hybrid cells.

Evidence has accumulated that classic L-type Ca2+ channel blockers with a dihydropyridine structure also inhibit T-type Ca2+ channels in certain types of central and peripheral neurons and in smooth muscle cells, albeit with a lower potency. Thus beneficial therapeutic effects of dihydropyridines in cardiovascular and neurological diseases may not only be associated with L-type but also with T-type Ca2+ channel blockade. Little is known about the exact order of potency of dihydropyridine derivatives at T-type Ca2+ channels. Here we investigate the efficacy and potency of four therapeutically used compounds, i.e. nifedipine, nimodipine, nicardipine, niguldipine, in the neuroblastoma-glioma cell line NG108-15. For comparative purposes the Ca2+ channel agonist Bay K 8644 was included. Ca2+ channel currents were measured with the whole-cell voltage clamp technique. Subtype Ca2+ channel currents were separated by clamp protocol and selective blockers. T-type Ca2+ channel currents were inhibited with decreasing potency in the order niguldipine > nicardipine > nimodipine > nifedipine (IC50-values 244 nM, 2.5 microM, 9.8 microM, 39 microM), whereas L-type Ca2+ channel currents were blocked with similar potency (IC50 for nicardipine 75 nM). Bay K 8644 increased T-type Ca2+ channel current at nanomolar concentrations (i.e. 95 +/- 16% increase by 300 nM). T-type Ca2+ channel block was completely reversible with exception of the block by niguldipine. Our results indicate a variability of two orders of magnitude in potency of T-type Ca2+ channel block by the dihydropyridine derivatives investigated. It is speculated that the relation between the L- and T-type Ca2+ channel block may determine the therapeutic profile of a dihydropyridine derivative.

A general program to estimate gene-frequencies by the method of maximum-likelihood.

The program estimates the optimal gene-frequencies from observed values of phenotypes by the method of maximum-likelihood. The program does not make assumptions about a specific blood-group-system. This information has to be supplied by input cards. A straightforward iteration process is used for obtaining initial estimates for the gene-frequencies in question. Then an iterative application of the Newton-Raphson method is used to solve the maximum-likelihood equations. The program yields the gene-frequencies and their standard deviations, expected values of the phenotypes, expected values of the genotypes. Finally the chi-square between observed frequencies and (optimal) expected values of phenotypes is computed.

A data structure model for a health information system.

The Ministry of Health and Environmental Control of Berlin is developing a Health Information System (HIS) on the basis of a multi-satellite network system, comprising a central, regional, local and functional unit level. The main part of this paper describes the conceptual structure of the Common Data Base (CDB) of HIS with special regard to the patient-oriented medical information originating from the various institutions of the health care system. This structure comprises the following five levels: 1. PATIENT 2. PROBLEM 3. CASE 4. EVENT 5. ACT Each of the levels represents a node in the structure model. A node is an entity with a set of "local properties" being specified for each level, referring to selected data on inferior levels. The structures of these five levels are described in detail. In the last part, so-called "data-manipulation procedures" are treated. These are descriptions covering any data manipulation and represent the basis of data integrity through system controlled transaction with the data base.

A DATA MANAGER for the health information system Berlin.

The needs for permanently changing the logical and physical structure of a medical datebase during the development of a health information system have initiated the project of implementing a DATA MANAGER. The concept of the DATA MANAGER covers facilities for the development of the logical data structure model including documentation of the model and programming support for application programs accessing the health information system (HIS) database. The outstanding facilities of the INTERLISP system have been found to be appropriate for writing the DATA MANAGER. A first data structure model, on which the DATA MANAGER will operate, is roughly outlined.