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Geographical distribution and density of Ixodes dammini (Acari: Ixodidae) and relationship to Lyme disease transmission in New Jersey.

As part of continuing studies of Lyme disease, deer were surveyed during three hunting seasons in 1981 to obtain information on geographic distribution and density of I. dammini in New Jersey. I. dammini occurred throughout central and southern New Jersey. Four deer management zones (DMZs) were shown to have high tick densities. Geographical distribution and density data were independently regressed against 25 environmental and physical factors. Elevation was shown to be the most important factor in explaining the variability in both I. dammini distribution and density. Lyme disease cases were closely associated with the distribution of I. dammini and 57.3 percent of 117 Lyme disease cases occurred in the four DMZs previously identified as having the highest tick density.

Animals↗

Designing fault-tolerant distributed archives for picture archiving and communication systems.

PURPOSE: Distributed archives in a picture archiving and communication system (PACS) environment can provide added fault tolerance and fail-over capability, as well as increased load capacity at a more economical price than traditional 'high-availability" systems. Systems can be configured with varying levels of fault tolerance, depending on the amount of redundancy desired. There is, however, a direct correlation between the level of hardware redundancy and cost to implement. This presentation details the system design for fault-tolerant distributed archives as well as several options for redundancy, referencing implementation of a fault-tolerant archive system at the University of Utah. METHODS: The distributed archive system described here is based on Image Devices' image archive software, which can be implemented on multiple individual archive servers in order to distribute archive functionality and operational load. The configuration and implementation of the individual servers together make up the distributed archive system and does not impact the ability of the system to be scaled to meet future requirements. Several implementation and configuration options exist, including the ability for servers to maintain replicated databases containing patient and image information. Thus, each archive can be aware of all information and the location of this information within the distributed archive system. RESULTS: The goal is to produce systems that will still be operational in the event of any single point of failure, ie, a network connection failure between facilities or the failure of a single archive server within the distributed system. During normal operation, workload for image acquisition, image routing and image query requests will be distributed between the archive servers. If the system is deployed in a multifacility environment, each archive server can be configured to be responsible for the acquisition and image distribution management within that server's local facility. If the system is deployed in a single facility environment, load can be distributed evenly between the archive servers based on an understanding of the workload requirements generated be each acquisition and display device in the system. In the event that an archive server fails, other archive servers within the system will have the ability to provide some or all of the failed server's functionality. The degree of fail-over capability is dependent on the archive server's configuration as well as hardware redundancy employed. Three levels of fault-tolerant design can be achieved with this system architecture: (1) duplicate work capability only; (2) duplicate work capability and short-term image cache; (3) duplicate work capability, short-term image cache, and longterm image archival. Using the basic fault-tolerant design above, we have implemented a multifacility distributed archive system at the University of Utah. This system was implemented at a fraction of the cost of true "high-availability" archive architectures yet provides constant up time for the PACS system. If the network connection between the two locations goes down, each site is still fully functional for soft-copy read, as well as image acquisition and distribution. If either of the archive servers goes down, the image sources are redirected to the other archive server. The operational server then handles image distribution for both locations. Access to images in the short-term image cache is available to both archive servers and is not affected by loss of the network connection or remote server. Because there is ony one long-term archive device, the ability to retrieve images from long-term storage is the only function compromised by a network or server failure. CONCLUSION: By implementing distributed archives in a PACS environment, it is possible to achieve a highly fault-tolerant system without the expense of high-availability hardware and software. The design concepts outlined here can be applied to any PACS system that supports distributed archive functionality.

Computer Systems↗

The hospital information system as a source for the planning and feed-back of specialized health care.

1. INTRODUCTION. In university hospitals, choices are made to which extend specialized health care will be supported. It is characteristic, for this type of care, that it takes place in a process of the continual advance of medical technology and the growing awareness by consumers and payors. Specialized healthcare contributes to the hospital qualifiers having a political and strategic impact. The hospital board needs information for planning and budgeting these new tasks. Much of the information will be based on data stored in the Hospital Information System (HIS). Due to load limitations, instant retrieval is not preferred. A separate executive information system, uploaded with HIS data, features statistics, on a corporate level, with the power to drill-down to detailed levels. However, the ability to supply information on new types of healthcare is limited since most of these topics require a flexible system for new dedicated cross-sections, like medical treatment from several specialisms and functional levels. 2. DATA RETRIEVAL AND DISTRIBUTION. During the information analysis, details were gathered on the necessary working procedures and the administrative organization, including the data registration in the HIS. In the next phase, all relevant data was organized in a relational datamodel. For each topic of care, dedicated views were developed at both low and high aggregation levels. It revealed that a matching change of the administrative organization was required, with an emphasis on financial registration aspects. For the selection of relevant data, a bottom-up approach was applied, which was based on the registrations starting from the patient administrative subsystem, through several transactional systems, ending at the general ledger in the HIS. Data on all levels was gathered, resulting in medical details presented in quantities, up to financial figures expressed in amounts of money. This procedure distinguishes from the predefined top-down techniques generally used for management and executive information systems. Data was regularly collected from the HIS, then converted and reorganized into relational datasets using XBase protocols. After having performed central quality controls and privacy protection measures, the datasets were distributed electronically to local PCs. Standard low-cost software packages enable analyses by user-friendly selection and presentation facilities. 3. EVALUATION. The method developed for data retrieval is flexible and easy to implement. If all basic data is registered in the HIS, the procedure can be applied for all strategic hospital functions that require planning and controlling during a certain time. Critical success factors and pitfalls will be presented in the poster. Using one consistent dataset, the information required about production and budget is presented at several functional levels and is quantified in units familiar to that level. The motivation for fast and accurate registration in the HIS was improved from the moment the medical and administrative staff recognized their own data in the feed-back on specialized health care.

Decision Making, Organizational↗

Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog.

Cholesterol is an important constituent of most mammalian cell membranes and its concentration in various cellular membranes is tightly regulated. Although there is much information about cholesterol distribution and trafficking in cells, it is primarily derived from indirect measurements, and the results obtained using different approaches are often conflicting. A cholesterol analog that faithfully mimics the properties of cholesterol and can be followed in living cells would thus be very useful. In this study, we report the fluorescence imaging of such an analog, dehydroergosterol (DHE), in living cells. DHE differs from cholesterol in having three additional double bonds and an extra methyl group. In model systems, DHE closely mimics the behavior of native cholesterol. Using triple-labeling studies, we show that DHE colocalizes extensively with endocytosed transferrin, an endocytic recycling compartment marker, and with a marker for the trans-Golgi network, Tac-TGN38. This distribution of DHE is qualitatively similar to that observed when cells are labeled with the fluorescent cholesterol-binding polyene antibiotic, filipin, although there are differences in apparent proportions of DHE and filipin that are localized at the plasma membrane. Another cholesterol derivative, 25-NBD-cholesterol, has a structure that is compromised by the presence of a bulky NBD group and does not distribute to the same organelles as DHE or filipin. In addition, we show in this manuscript that kinetic processes can be followed in living cells by monitoring recovery of DHE fluorescence in a photobleached region over time. Our observations provide evidence for the presence of a large intracellular cholesterol pool in the endocytic recycling compartment and the trans-Golgi network that might play important roles in the trafficking of lipids, lipid-anchored proteins, and transmembrane proteins that preferentially partition into cholesterol-enriched membrane domains. In addition, this intracellular cholesterol pool might be involved in the maintenance of cellular cholesterol homeostasis.

4-Chloro-7-nitrobenzofurazan↗

Open Access to essential health care information.

Open Access publishing is a valuable resource for the synthesis and distribution of essential health care information. This article discusses the potential benefits of Open Access, specifically in terms of Low and Middle Income (LAMI) countries in which there is currently a lack of informed health care providers - mainly a consequence of poor availability to information. We propose that without copyright restrictions, Open Access facilitates distribution of the most relevant research and health care information. Furthermore, we suggest that the technology and infrastructure that has been put in place for Open Access could be used to publish download-able manuals, guides or basic handbooks created by healthcare providers in LAMI countries.

Journal Article↗

BioRAT: extracting biological information from full-length papers.

MOTIVATION: Converting the vast quantity of free-format text found in journals into a concise, structured format makes the researcher's quest for information easier. Recently, several information extraction systems have been developed that attempt to simplify the retrieval and analysis of biological and medical data. Most of this work has used the abstract alone, owing to the convenience of access and the quality of data. Abstracts are generally available through central collections with easy direct access (e.g. PubMed). The full-text papers contain more information, but are distributed across many locations (e.g. publishers' web sites, journal web sites and local repositories), making access more difficult. In this paper, we present BioRAT, a new information extraction (IE) tool, specifically designed to perform biomedical IE, and which is able to locate and analyse both abstracts and full-length papers. BioRAT is a Biological Research Assistant for Text mining, and incorporates a document search ability with domain-specific IE. RESULTS: We show first, that BioRAT performs as well as existing systems, when applied to abstracts; and second, that significantly more information is available to BioRAT through the full-length papers than via the abstracts alone. Typically, less than half of the available information is extracted from the abstract, with the majority coming from the body of each paper. Overall, BioRAT recalled 20.31% of the target facts from the abstracts with 55.07% precision, and achieved 43.6% recall with 51.25% precision on full-length papers.

Abstracting and Indexing↗

Thallium-201 radioactive implant induced X-ray emission scanning of stable iodine distribution in thyroid--phantom experiment.

A new method has been developed for imaging the thyroid gland by the use of 201Tl radioactive implant induced X-ray emission (RIXE). The thyroid phantom was made from two cylindrical tubes embedded in plastic neck phantom. Each tube consisted of stable iodine and 201Tl radioactive source in 10 ml water solution. Some photopeaks in the energy range from 20 to 200 ke V were scanned along a horizontal axis by the collimated Ge detector with high energy resolution. The distribution on the horizontal axis was obtained for the generated I K alpha-ray and some primary 201Tl radiations. The 201Tl RIXE scanning can provide information about the distribution of iodine with 201Tl as well as 201Tl distribution in the thyroid gland. The effectiveness of the 201Tl RIXE technique as a thyroid scanning method is discussed.

Iodine↗

Radiographic information theory: correction for x-ray spectral distribution.

A more complete computational method is developed to account for the effect of the spectral distribution of the incident x-ray fluence on the minimum exposure required to record a specified information set in a diagnostic radiograph. It is shown that an earlier, less rigorous, but simpler computational technique does not introduce serious errors provided that both a good estimate of the mean energy per photon can be made and the detector does not contain an absorption edge in the spectral range. Also shown is that to a first approximation, it is immaterial whether the detecting surface counts the number of photons incident from each pixel or measures the energy incident on each pixel. A previous result is confirmed that, for mammography, the present methods of processing data from the detector utilize only a few percent of the incident information, suggesting that techniques can be developed for obtaining mammograms at substantially lower doses than those presently used. When used with film-screen combinations, x-ray tubes with tungsten anodes should require substantially lower exposures than devices using molybdenum anodes, when both are operated at their optimal voltage.

Humans↗

Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice.

Concentrative nucleoside transporters (Cnts) and equilibrative nucleoside transporters (Ents) have essential physiological functions and are important in disposition of anticancer and antiviral nucleoside analogs. Information on tissue distribution of Cnts and Ents in rodents is sparse. Thus, the present study aimed to determine the distribution of Cnt1-3 and Ent1-3 transcripts in 19 tissues of Sprague-Dawley rats and C57BL/6 mice of both genders. These six transcripts were quantified using the branched DNA signal amplification assay. Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species. Cnt2 mRNA was expressed highest in the small intestine of both rats and mice, intermediate in liver of rats but not in mice, and lower in thymus and spleen of both species. Cnt3 mRNA has marked species differences, with the highest expression in lung of rats but uterus of mice. Ent1 mRNA was most highly expressed in testes and lung of both species. Ent1 mRNA was highly expressed in liver and pituitary of mice, but not in rats. Ent2 mRNA was highly expressed in testes and brain of both species. Ent3 mRNA was highest in kidney, followed by testes, in both species. Significant gender differences were observed in kidney (mouse) and heart (rat). These studies demonstrate that in general, tissue distribution of Cnt and Ent is similar in rats and mice. However, a few important species and gender differences do exist, which could be responsible for related differences in efficacy and toxicity of substrates for these transporters.

Animals↗

In situ hybridization histochemistry in the human hypothalamus.

We have seen that mRNA for several neuropeptides can be visualized at the microscopic level in human post-mortem brain tissues using in situ hybridization histochemistry and oligonucleotides as probes. The specificity of the hybridization signal detected in each case is supported by several criteria such as Northern blot analysis, use of at least two oligonucleotides complementary to different regions of the same target mRNA, cohybridization of labeled and excess unlabeled oligonucleotide probes, and melting curve analysis of the formed hybrids. Furthermore, factors such as age, post-mortem delay or gender did not show a significant effect in the levels of hybridization in the control population studied. Hybridization signals comparable to those found in the control population were obtained in frozen tissues, stored for up to 6 years before analysis. The results obtained for the different neuropeptides examined are, in general, in good agreement with the available information on their distribution and cellular localization as determined by radioimmunoassay or immunohistochemistry. The use of in situ hybridization histochemistry has clearly revealed the location of neurons synthesizing these neuropeptides, adding important information to that provided by radioimmunoassay or immunohistochemistry. A typical example is the identification of peptide synthesizing neuronal cell bodies by immunohistochemistry. This requires, in some cases, the use of treatments such as colchicine, obviously impossible with human brain tissues. The abundance of mRNA could be further related to transcriptional activity and, when compared with peptide levels, can provide some clues on peptide turnover rates. Thus in the hypothalamus, the paraventricular and supraoptic nuclei were found to contain cells expressing arginine-vasopressin and oxytocin mRNAs. Their distribution was in good agreement with that determined by immunohistochemistry (Dierickx and Vandesande, 1977). We have also found that these nuclei contain transcripts for neuropeptide genes such as preproenkephalin A, neuropeptide Y and somatostatin, in agreement with previously reported immunohistochemical data (Agid and Javoy-Agid, 1985; Emson et al., 1986). In the basal ganglia, numerous cells heterogeneously distributed throughout the caudate and putamen nuclei were found to contain preproenkephalin A mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Basal Ganglia↗

Deniz: the electronic database for beta-thalassemia mutations in the Arab world.

OBJECTIVE: Data on the distribution of beta-thalassemia mutations in Arab populations are usually destined to disparate locations and much of these become increasingly difficult for an average researcher to locate. That is why we aimed at establishing an electronic database network, called Deniz, for beta-thalassemia allele frequency distributions in the Arab world at http://biobase.fatih.edu.tr. METHODS: The scheme of the database combines the benefits of the relational and hierarchical systems. Detailed statistics of the frequencies of beta-thalassemia mutations are retrieved in tabular forms. Multiple permanent connections allow flexible movement within the database. Queries are processed by the systems language and sent to the user's browser as hypertext markup language documents. RESULTS: The database catalogues the frequencies of beta-thalassemia mutations in 14 Arab countries as pooled from the analysis of 3,138 chromosomes by 36 laboratories. Of the 57 B-globin gene mutations reported in Arabs, IVS-I-110 (G-A), IVS-I-5 (G-C), IVS-I-6 (T-C), IVS-II-1 (G-A), and IVS-I-1 (G-A) are the most encountered and they account for approximately two thirds of the Arab chromosomes registered in Deniz. CONCLUSION: In addition to its importance as a hub of updated information on the distribution of beta-thalassemia mutations in Arabs, information in Deniz may be used to predict diagnostic strategies that may be offered to natives of unstudied countries. Incidence data may also give important clues on the possible origins of beta-thalassemia in the Arab world. The integration of Deniz with other databases is currently in process and researchers are invited to contribute to the growth of the database.

Alleles↗

Electrical measurement of fluid distribution in legs and arms.

Intra- and extra-cellular fluid distribution is very important to know the physiological and clinical state of living subjects. However, it is quite difficult to measure the distribution in vivo. Electrical impedance of living tissue is mainly affected by extra-cellular fluid at an applied frequency lower than the beta-dispersion frequency, and is affected by both extra- and intra-cellular fluid at higher applied frequencies than that. In this paper, we discuss the problems of measurement of intra- and extra-cellular fluid distribution in living tissues by means of electrical impedance. The intra- and extra-cellular fluid distribution is related to some physiological parameters, such as blood circulation, metabolism of tissues, and the electrolytic concentration of intra- and extra-cellular fluids. Therefore, the information about the distribution of fluids in tissues is quite useful for the diagnosis of various diseases, the monitoring of seriously ill patients, and in medical treatments such as artificial dialysis. We discuss the method of measurement and the results of experiments.

Arm↗

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution.

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the 'linear model' we assumed a linear relation between mineral content and Young's modulus of the tissue. In the 'exponential model' we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 microm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.

Adult↗

High resolution protein localization using soft X-ray microscopy.

Soft X-ray microscopes can be used to examine whole, hydrated cells up to 10 microm thick and produce images approaching 30 nm resolution. Since cells are imaged in the X-ray transmissive "water window", where organic material absorbs approximately an order of magnitude more strongly than water, chemical contrast enhancement agents are not required to view the distribution of cellular structures. Although living specimens cannot be examined, cells can be rapidly frozen at a precise moment in time and examined in a cryostage, revealing information that most closely approximates that in live cells. In this study, we used a transmission X-ray microscope at photon energies just below the oxygen edge (lambda = 2.4 nm) to examine rapidly frozen mouse 3T3 cells and obtained excellent cellular morphology at better than 50 nm lateral resolution. These specimens are extremely stable, enabling multiple exposures with virtually no detectable damage to cell structures. We also show that silver-enhanced, immunogold labelling can be used to localize both cytoplasmic and nuclear proteins in whole, hydrated mammary epithelial cells at better than 50 nm resolution. The future use of X-ray tomography, along with improved zone plate lenses, will enable collection of better resolution (approaching 30 nm), three-dimensional information on the distribution of proteins in cells.

3T3 Cells↗

Electrical measurement of fluid distribution in human legs: estimation of extra- and intra-cellular fluid volume.

In this paper, we discuss the problems of measurement of intra- and extra-cellular fluid distribution in living tissues by means of electrical impedance. The intra- and extra-cellular fluid distribution is related to some physiological parameters, such as blood circulation, metabolism of tissues, and the electrolytic concentration of intra- and extra-cellular fluids. Therefore, the information about the distribution of fluids in tissues is quite useful for the diagnosis of various diseases, the monitoring of seriously ill patients, and in medical treatments such as artificial dialysis. We discuss the method of measurement and the results of experiments.

Dialysis↗

Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM.

BACKGROUND: Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone. Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT. METHODS: Experiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images. RESULTS: The most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images. CONCLUSION: The combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred.

Journal Article↗

Electron microscopic studies of receptor localization.

The localization and density of G-protein-coupled receptors (GPCRs) on the cell surface is a critical factor for specifying signaling within and between neurons. GPCRs and their associated signaling components are localized to specific neuronal compartments that give rise to a variety of functional implications. Therefore, information regarding the precise localization of GPCRs is a prerequisite for studies designed to elucidate their contribution to neuronal function, and can be achieved only by immunoelectron microscopy. Three main techniques for immunoelectron microscopy exist: the preembedding immunoperoxidase, the preembedding immunogold, and the postembedding immunogold techniques. The preembedding immunogold method is reliable for the localization of receptors at extrasynaptic and perisynaptic sites. The preembedding immunoperoxidase method provides valuable information on regional distribution of receptors. Finally, to localize any receptor at synaptic sites the only reliable method is the postembedding immunogold technique. Therefore, the three immunocytochemical methods provide complementary information about the cellular, subcellular, and subsynaptic location of any receptor.

Animals↗

Subunit composition, distribution and function of GABA(A) receptor subtypes.

GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain and are the site of action of many clinically important drugs. These receptors are composed of five subunits that can belong to eight different subunit classes. Depending on their subunit composition, these receptors exhibit distinct pharmacological and electrophysiological properties. Recent studies on recombinant and native GABA(A) receptors suggest the existence of far more receptor subtypes than previously assumed. Thus, receptors composed of one, two, three, four, or five different subunits might exist in the brain. Studies on the regional, cellular and subcellular distribution of GABA(A) receptor subunits, and on the co-localization of these subunits at the light and electron microscopic level for the first time provide information on the distribution of GABA(A) receptor subtypes in the brain. These studies will have to be complemented by electrophysiological and pharmacological studies on the respective recombinant and native receptors to finally identify the receptor subtypes present in the brain. The distinct cellular and subcellular location of individual receptor subtypes suggests that they exhibit specific functions in the brain that can be selectively modulated by subtype specific drugs. This conclusion is supported by the recent demonstration that different GABA(A) receptor subtypes mediate different effects of benzodiazepines. Together, these results should cause a revival of GABA(A) receptor research and strongly stimulate the development of drugs with a higher selectivity for alpha2-, alpha3-, or alpha5-subunit-containing receptor subtypes. Such drugs might exhibit quite selective clinical effects.

Animals↗