Functional neurosurgery using 3-D computer stereotactic atlas.

To facilitate a full-scale representation of thalamic nuclei and surrounding subcortical structures in the course of stereotactic procedures, a 3-D computer atlas of this region has been created, which permits visualization of the operative field including the involved structures and the position of the instrument. Necessary adaptation is performed according to the position of the intracranial reference points derived from CT-scan. Working with the atlas permitted more accurate and safer surgery. An IBM PC/AT computer was used.

[The CT-stereotaxic neutron brachytherapy of brain tumors with californium sources on the ANET-B apparatus]. / KT-stereotaksicheskaia neitronnaia brakhiterapiia opukholei golovnogo mozga kalifornievymi istochnikami na apparate "ANET-B".

A method for stereotaxic intratissue radiotherapy of brain tumors based on the findings of computed tomography is described. Radiosurgical implantation of sources with increased 252Cf content emitting mixed neutron + gamma-radiation was accomplished by means of an ANET-B apparatus by the afterloading method. Neutron irradiation is particularly effective in patients with malignant tumors possessing a large fraction of cells in a state of deep anoxia. Dosimetric planning was conducted by means of an original computer system. Devices and radiation-technical equipment for adaptation of the ANET-B apparatus for irradiation of neurosurgical patients are described. The indications for the use of this method and its place among the complex of measures for the treatment of patients with new growths of the brain are discussed. The first experience in using CT-stereotaxic neutron brachytherapy with californium sources on the ANET-B apparatus for the treatment of 6 patients with malignant glial tumors of the brain is dwelt on.

[Intraoperative monitoring of the EEG in patients with arterial aneurysms of the cerebral vessels]. / Intraoperatsionnyi monitoring EEG u bol'nykh s arterial'nymi anevrizmami sosudiv mozga.

Visual EEG monitoring and EEG monitoring using a special "Neuro-2" monitor controlling the changes in quantitative EEG parameters (power range and coherence) have been used during surgery in 42 patients with arterial aneurysms of brain vessels performed in conditions of profound controlled arterial hypotension. Computer processing facilitates EEG analysis and reveals the most early signs of the developing cerebral ischemia on the basis of specific changes in power ranges and coherence.

A polymer carrier system for taste masking of macrolide antibiotics.

A polymer carrier system was developed to reduce the bitterness of erythromycin and its 6-O-methyl derivative, clarithromycin, by absorption to Carbopol. The mechanism involves ionic bonding of the amine macrolide to the high molecular weight polyacrylic acid, thereby removing the drug from the solution phase in an ion-free suspension. After ingestion, endogenous cations displace the drug from the polymer in the gastrointestinal tract to achieve bioavailability. The macrolide-Carbopol complexes were prepared by dissolving or slurrying predetermined ratios of drug and polymer in water or hydroalcoholic mixtures. A series of in vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for the various drug-polymer ratios. Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings. Hydroxypropyl methylcellulose phthalate (HP-55) provided the best combination of suspension stability, taste protection and bioavailability. Human bioavailability studies demonstrated that the microencapsulated Carbopol absorbates of erythromycin and clarithromycin gave blood levels comparable to those obtained from conventional solid formulations.

3-D computer model of subcortical structures of human brain.

Three-dimensional computer model of thalamus and adjacent formations of human brain has been elaborated on the basis of sagittal slices from the Schaltenbrand-Bailey stereotactic atlas. The model includes 120 morphologically distinguishable structures and consists of more than 16 million points (volume elements) each of them being associated with the particular structure in the brain. The model is stored in the long-term computer memory. A special software has been developed to facilitate utilizing the model obtained. The software facilitates synthesizing arbitrary cross-sections through the brain and provides the correspondence between the stereotactic coordinates of any point and its position on the screen of monitor. The coordinates of the point in the system of stereotactic atlas and the name of the structure, the point belongs to, are also supplied. It is also possible to get magnified images of cross-sections and to get isometrical images. The system enables the neurosurgeon to improve the planning and execution of stereotactic operations, and will also be helpful for education.

[Computerized system of dosimetric planning of interstitial multiposition stereotaxic irradiation in neutron therapy of brain tumors]. / Kompiuternaia sistema dozimetricheskogo planirovaniia vnutritkanevogo mnogopozitsionnogo stereotaksicheskogo oblucheniia pri neitronnoi terapii opukholei golovnogo mozga.

A computerized system PLUT-B intended for a dosimetric design of stereotaxic neutron brachytherapy of brain tumors, was developed. It is capable of simulating dose distribution in various parameters of irradiation, manipulating them, retaining the surgical aspects within the field of vision, and arriving at an acceptable dosimetric plan. The system permits visualization of a target with an applied dose field in the multiwindow mode, layer-by-layer vision in any direction, displaying a scheme of implantation, and drawing up of maps of isodose distributions. It is intended to be used by a physician, convenient in operation, the time at the design stage is 35-40 minutes.

Asymmetric synthesis and properties of the enantiomers of the antibacterial agent 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6- fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride.

Compound 1 [7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-f luoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride] is a potent member of the quinolonecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation. We have developed efficient asymmetric syntheses of the enantiomers of this agent. The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro. The enantiomer 1a shows significantly better in vivo activity in a Pseudomonas aeruginosa mouse protection model compared to racemic 1. Coupled with the improved solubility profile of 1a relative to racemic material, these features may be of practical significance from a clinical standpoint.

[Dynamics of the spectral-coherent characteristics of the human EEG in healthy subjects and brain pathology]. / Dinamika spektral'no-kogerentnykh kharakteristik EEG cheloveka v norme i pri patologii mozga.

EEGs of 15 healthy subjects and 30 patients in early period after surgical ablation of tumours with basal localization, were investigated by means of monitor "Neuro-1" which allows to obtain in continuous regime characteristics of EEG dynamics according to power spectra and reveal the characteristics of intercentral relations of electrical brain processes by coherence and phase shifts. In healthy subjects in the period of transition from wakefulness to drowsiness highly coherent beta-rhythm (16-18 Hz) was revealed, preceeding typical picture of drowsiness and sleep. Study of the patients shows that certain characteristics of coherence and phasic shifts have an important prognostic value. Conclusion is made that for estimation of the functional state of healthy subjects during transition from wakefulness to drowsiness and of patients in early postoperative period the data on spectra of coherence are most informative.

In vitro and in vivo considerations of a novel matrix-controlled bovine progesterone-releasing intravaginal device.

An in vitro system measuring progesterone release from silicone matrixes into serum is described. Drug release followed a matrix-controlled diffusion model in which the cumulative quantity released was linear with the square root of time. A bovine intravaginal device, consisting of a steel coil coated on both sides with a progesterone silicone matrix, was used as an in vivo drug delivery system. In vivo drug release also was matrix controlled, with rates comparable to those obtained in vitro. However, lag times of 1.7 and 4.2 days before reaching the steady-state rate were obtained for the outer and inner surfaces, respectively. The combination of effects resulted in a pseudo-zero-order drug-releasing device in which cumulative drug released was linear with time for at least 16 days.

Stable nonaqueous pentobarbital sodium solutions for use in laboratory animals.

The degradation kinetics of pentobarbital sodium in propylene glycol-based solutions were studied along with the in vivo effects in laboratory animals. The degradation rate constant was directly proportional to the water concentration in propylene glycol-water solvent systems. An activation energy of 23.4 kcal/mole was obtained in propylene glycol-water (1:1). Pentobarbital sodium solutions in anhydrous propylene glycol and 9:1 mixtures of propylene glycol with ethanol, glycerin, or dimethylacetamide gave relatively slow degradation rates at 100 degrees with all projected 25 degrees t 99% values greater than 4.5 years. Intravenous administration of pentobarbital sodium in various anhydrous propylene glycol-based vehicles to rats produced no hemolysis of gross organ damage that would interfere with pathological evaluations. Results of an intraperitoneal sleeptime study indicated that pentobarbital sodium produced consistent hypnotic effect when administered as an aqueous solution or in anhydrous propylene glycol-based vehicles.

Linear drug release from laminated hydroxypropyl cellulose-polyvinyl acetate films.

Release of drug from a single-layer film containing dispersed drug follows a diffusion-controlled matrix model, where the quantity released per unit area is proportional to the square root of time. The kinetics may be made linear with time (zero order) by laminating a second film without drug to the releasing side of the film with dispersed drug. In this manner, the drug layer serves as a reservoir and controls the duration of drug release, while the nondrug layer functions as a rate-controlling membrane. Zero-order drug release was demonstrated in such laminated films using 18-45 percent pentobarbital, methapyrilene, or salicylic acid contained in hydroxypropyl cellulose as the reservoir layer and mixtures of hydroxypropyl cellulose and polyvinyl acetate as the membrane layer. Inverse relationships between the release rate and membrane thickness and between the logarithm of the rate and the percentage of polyvinyl acetate in the membrane layer were observed. Of the three drugs tested, salicylic acid gave the fastest release rates while pentobarbital gave the slowest.