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Biomedical subjects

D Horn

Publications and source records attributed to D Horn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intraoperative electromyogram monitoring of the recurrent laryngeal nerve: experience with an intralaryngeal surface electrode. A method to reduce the risk of recurrent laryngeal nerve injury during thyroid surgery.

INTRODUCTION: A clinical method to localize the recurrent laryngeal nerve intraoperatively in order to minimize the risk of accidental injury is presented. METHODS AND RESULTS: By means of an electrode, the nerve was stimulated by a pulsed contact current. The resulting muscle potential was detected using an electrode placed in the larynx. We applied this technique during the time period between 1 January 1997 and 31 December 1998. In 96 cases of primary thyroid resection, the recurrent nerve was identified 167 times. The patients were operated on for nodular thyroid (n=85), Grave's disease (n=9) and malignant papillary goiter (n=2). Retrospectively, the rate of intraoperative nerve injury, equivalent to the rate of postoperative transient and permanent nerve palsy, was 1.04% in the 96 patients and 0.60% with respect to the 167 nerves at risk. The rate of failure of the method was 7.29%.

Electrodes, Implanted↗
PubMed1999

Ellis-van Creveld syndrome: examination at 15 weeks' gestation.

In 1940, Ellis and van Creveld defined a syndrome they referred to as chondro-ectodermal dysplasia. This autosomal recessive condition, now usually referred to as Ellis-van Creveld syndrome (EVC), comprises bilateral postaxial polydactyly, a chondrodysplasia, characterized by shortness of limbs, and ectodermal dysplasia. Congenital heart defects are also common. There are many reports in medical literature describing affected newborns and even, older children. Here, we report the clinical, radiological and histological findings in a 15-week-old affected fetus. The diagnosis of Ellis-van Creveld syndrome in this fetus is based on a positive family history (an affected sib) and shortness of long bones as well as hexadactyly diagnosed by prenatal ultrasonography. On post-mortem examination, bilateral postaxial hexadactyly and symmetrical shortness of the long bones was noted. Histologically, there was too short a zone of cartilagineous columns in the metaphyses, a reduced number of chondrocytes and an irregularly structured spongiosa within the ossification zone. In addition, the fetus was found to have an atrio-ventricular canal. This heart defect is presumably rare in this syndrome. Other characteristic features such as small and dysplastic nails, sparse hair and abnormalities of the teeth were, of course, not yet present in this early developmental stage. In addition to EVC, the fetus had a 47,XXY chromosome constitution.

Adult↗
PubMed1998

Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella.

CONTEXT: Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades. OBJECTIVE: To determine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella. DESIGN: A before-after comparative 2-year trial. SETTING: A 500-bed, university-affiliated community hospital in Queens, NY. PATIENTS: All adult medical and surgical hospital inpatients. INTERVENTION: A new antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection. All other cephalosporin use required prior approval by the infectious disease section. MAIN OUTCOME MEASURE: Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period). RESULTS: An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995. This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001). A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01). All such isolates except one were susceptible to other antibiotics. CONCLUSION: Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization. This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents. Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.

Adult↗
PubMed1998

Fast temporal encoding and decoding with spiking neurons.

We propose a simple theoretical structure of interacting integrate-and-fire neurons that can handle fast information processing and may account for the fact that only a few neuronal spikes suffice to transmit information in the brain. Using integrate-and-fire neurons that are subjected to individual noise and to a common external input, we calculate their first passage time (FPT), or interspike interval. We suggest using a population average for evaluating the FPT that represents the desired information. Instantaneous lateral excitation among these neurons helps the analysis. By employing a second layer of neurons with variable connections to the first layer, we represent the strength of the input by the number of output neurons that fire, thus decoding the temporal information. Such a model can easily lead to a logarithmic relation as in Weber's law. The latter follows naturally from information maximization if the input strength is statistically distributed according to an approximate inverse law.

Action Potentials↗
PubMed1998

Probability Density Estimation Using Entropy Maximization.

We propose a method for estimating probability density functions and conditional density functions by training on data produced by such distributions. The algorithm employs new stochastic variables that amount to coding of the input, using a principle of entropy maximization. It is shown to be closely related to the maximum likelihood approach. The encoding step of the algorithm provides an estimate of the probability distribution. The decoding step serves as a generative mode, producing an ensemble of data with the desired distribution. The algorithm is readily implemented by neural networks, using stochastic gradient ascent to achieve entropy maximization.

Journal Article↗
PubMed1998

Memory maintenance via neuronal regulation.

Since their conception half a century ago, Hebbian cell assemblies have become a basic term in the neurosciences, and the idea that learning takes place through synaptic modifications has been accepted as a fundamental paradigm. As synapses undergo continuous metabolic turnover, adopting the stance that memories are engraved in the synaptic matrix raises a fundamental problem: How can memories be maintained for very long time periods? We present a novel solution to this long-standing question, based on biological evidence of neuronal regulation mechanisms that act to maintain neuronal activity. Our mechanism is developed within the framework of a neural model of associative memory. It is operative in conjunction with random activation of the memory system and is able to counterbalance degradation of synaptic weights and normalize the basins of attraction of all memories. Over long time periods, when the variance of the degradation process becomes important, the memory system stabilizes if its synapses are appropriately bounded. Thus, the remnant memory system is obtained by a dynamic process of synaptic selection and growth driven by neuronal regulatory mechanisms. Our model is a specific realization of dynamic stabilization of neural circuitry, which is often assumed to take place during sleep.

Animals↗
PubMed1998

Oculo-facio-cardio-dental (OFCD) syndrome.

The association of facial dysmorphy, congenital cataracts, microphthalmia, heart disease, and dental radiculomegaly is very rare. We describe a girl with atrial septal defect, unilateral congenital cataract, unilateral microphthalmia, radiculomegaly of incisor and canine teeth with open apices and other dental crown anomalies. This combination of symptoms clearly represents a distinct syndrome and has recently been described as oculo-facio-cardio-dental (OFCD) syndrome.

Abnormalities, Multiple↗
PubMed1998

Associative memory and segmentation in an oscillatory neural model of the olfactory bulb.

We discuss the first few stages of olfactory processing in the framework of a layered neural network. Its central component is an oscillatory associative memory, describing the external plexiform layer, that consists of inhibitory and excitatory neurons with dendrodendritic interactions. We explore the computational properties of this neural network and point out its possible functional role in the olfactory bulb. When receiving a complex input that is composed of several odors, the network segments it into its components. This is done in two stages. First, multiple odor input is preprocessed in the glomerular layer via a decorrelation mechanism that relies on temporal independence of odor sources. Second, as the recall process of a pattern consists of associative convergence to an oscillatory attractor, multiple inputs are identified by alternate dominance of memory patterns during different sniff cycles. This could explain how quick analysis of mixed odors is subserved by the rapid sniffing behavior of highly olfactory animals. When one of the odors is much stronger than the rest, the network converges onto it, thus displaying odor masking.

Animals↗
PubMed1998

Studies of the continuing susceptibility of group A streptococcal strains to penicillin during eight decades.

BACKGROUND: In view of the widespread use of penicillin for >50 years for the treatment of group A streptococcal infections, we examined the question of whether there has been a change in susceptibility to penicillin in group A streptococcal strains collected during a span of 80 years (1917 to 1997). METHODS: One hundred thirty-three group A streptococcal strains collected during 80 years were tested for changes in penicillin susceptibility. Three tests were used: (1) the microtiter broth minimal inhibitory concentration (MIC); (2) the minimal bactericidal concentration (MBC); and (3) the penicillin E strip MIC. RESULTS: The results indicate there has been no change in the susceptibility to penicillin in these group A streptococci during the past 80 years. The microtiter broth MIC90 for the oldest strains (0.032 microg/ml) was not significantly different from those collected most recently (0.032 microg/ml); there is no statistical difference between the raw MIC data for the four collection periods (P=0.468, analysis of variance on ranks). CONCLUSIONS: There has been no change in the susceptibility of group A streptococci during this time in spite of well-documented cases of penicillin resistance in other Gram-positive organisms and despite recognized resistance of group A streptococci to other antibiotics.

Anti-Bacterial Agents↗
PubMed1998

Neuronal regulation versus synaptic unlearning in memory maintenance mechanisms.

Hebbian learning, the paradigm of memory formation, needs further mechanisms to guarantee creation and maintenance of a viable memory system. One such proposed mechanism is Hebbian unlearning, a process hypothesized to occur during sleep. It can remove spurious states and eliminate global correlations in the memory system. However, the problem of spurious states is unimportant in the biologically interesting case of memories that are sparsely coded on excitatory neurons. Moreover, if some memories are anomalously strong and have to be weakened to guarantee proper functioning of the network, we show that it is advantageous to do that by neuronal regulation (NR) rather than synaptic unlearning. Neuronal regulation can account for dynamical maintenance of memory systems that undergo continuous synaptic turnover. This neuronal-based mechanism, regulating all excitatory synapses according to neuronal average activity, has recently gained strong experimental support. NR achieves synaptic maintenance over short time scales by preserving the average neuronal input field. On longer time scales it acts to maintain memories by letting the stronger synapses grow to their upper bounds. In ageing, these bounds are increased to allow stronger values of remaining synapses to overcome the loss of synapses that have perished.

Adult↗
PubMed1997

Position-dependent and promoter-specific regulation of gene expression in Trypanosoma brucei.

Trypanosoma brucei evades the mammalian immune response by a process of antigenic variation. This involves mutually exclusive and alternating expression of telomere-proximal variant surface glycoprotein genes (vsgs), which is controlled at the level of transcription. To examine transcription repression in T.brucei we inserted reporter genes, under the control of either rRNA or vsg expression site (ES) promoters, into various chromosomal loci. Position-dependent repression of both promoters was observed in the mammalian stage of the life cycle (bloodstream forms). Repression of promoters inserted into a silent ES was more pronounced closer to the telomere and was bi-directional. Transcription from both ES and rRNA promoters was also efficiently repressed at a non-telomeric vsg locus in bloodstream-form trypanosomes. In cultured tsetse fly midgut-stage (procyclic) trypanosomes, in which vsg is not normally expressed, all inserted rRNA promoters were derepressed but ES promoters remained silent. Our results suggest that vsg promoters and ectopic rRNA promoters in bloodstream-form T.brucei are restrained by position effects related to their proximity to vsgs or other features of the ES. Sequences present in rRNA promoters but absent from vsg ES promoters appear to be responsible for rRNA promoter-specific derepression in procyclic cells.

Animals↗
PubMed1997

Solitary waves of integrate-and-fire neural fields.

Arrays of interacting identical neurons can develop coherent firing patterns, such as moving stripes that have been suggested as possible explanations of hallucinatory phenomena. Other known formations include rotating spirals and expanding concentric rings. We obtain all of them using a novel two-variable description of integrate-and-fire neurons that allows for a continuum formulation of neural fields. One of these variables distinguishes between the two different states of refractoriness and depolarization and acquires topological meaning when it is turned into a field. Hence, it leads to a topologic characterization of the ensuing solitary waves, or excitons. They are limited to pointlike excitations on a line and linear excitations, including all the examples noted above, on a two-dimensional surface. A moving patch of firing activity is not an allowed solitary wave on our neural surface. Only the presence of strong inhomogeneity that destroys the neural field continuity allows for the appearance of patchy incoherent firing patterns driven by excitatory interactions.

Cell Communication↗
PubMed1997

Mitogenic lectin concanavalin A induces calvarial bone formation in vivo via indomethacin-sensitive pathway.

Natural products such as plant lectins have not been extensively surveyed for their potential as anabolic agents. Wlodarski (1991) observed that the lectin Concanavalin A (ConA) has chondrogenic and osteogenic activity following local injection over the mouse tibia. To gain more insight into the mechanism of ConA in bone, we investigated and quantitated the effects of ConA injected locally over the mouse calvaria in vivo. ConA was injected subcutaneously over the calvaria of mice at 2, 10, and 20 microg per injection, four times a day, for three consecutive days. By day fourteen, a layer of new woven bone 30 microm thick had been laid down on the periosteal surface, resulting in a 36% increase in calvarial thickness (as compared with 2% in vehicle-treated controls). ConA also increased periosteal width and osteoblast surface in a dose-dependent manner. Concurrent administration of indomethacin (30 microg) with ConA (20 microg), four times a day for 3 days, strongly inhibited new bone formation. With a single injection of ConA (80 microg) over the calvaria, osteoclastic bone resorption and proliferation of osteoblast precursors and periosteum increased at day four, but showed a decrease at later times (14 and 28 days after injection). Except at the earliest time, there was little evidence of osteoclastic bone resorption. New bone width increased linearly over 28 days. In summary, ConA induced new bone formation in a pattern comparable with that of aFGF and bFGF, potent stimulators of calvarial bone formation (Dunstan, 1993), and this osteogenic effect was caused by an indomethacin-sensitive pathway.

Animals↗
PubMed1997

Effects of human tumor cell lines on local new bone formation in vivo.

Although some tumors cause osteolytic lesions, there are some that stimulate new bone formation. This is an important phenomenon because the responsible mechanisms probably represent an aberration of normal physiological bone formation, and identifying the factors involved in the process may lead to new therapies for various bone diseases. To clarify our understanding of the potential mechanism responsible, we compared and quantitated the extent of new bone formation stimulated by human tumors (HeLa, Hep-2, AV-3, FL, WISH and KB), some of which have osteogenic activity in vivo [2]. Tumor cells were injected over the calvaria of nude mice to examine formation of new bone. The tumor cells produced three histologically distinct patterns of new bone growth: (1) WISH and KB stimulated appositional bone growth adjacent to periosteal bone surfaces; (2) HeLa and Hep2 induced new bone growth over calvarial surface even when distant from the tumor mass; (3) FL stimulated bone formation adjacent to periosteum as well as ectopic bone formation in sites distant from bone. All tumors except AV3 induced mean new bone thickness >100 microm, and Hep-2 cells produced bone 330 microm thick. PCR and Northern blot analysis of mRNA isolated from cultured tumor cells revealed that all cell lines expressed mRNA for TGFbeta, (fibroblast growth factor) FGF-1, FGF-2, and IGF-I, and most cell lines produced mRNA for PDGF. Only FL expressed large amounts of mRNA for BMP2. In serum-free conditioned media from Hep2 and HeLa cells purified by heparin affinity chromatography, we have identified FGF-I, FGF-2, and PDGF by immunodetection with specific antibodies. Our results show that new bone growth caused by these tumors is likely due to the production of bone growth factors by the tumor cells, and that the overall effects on bone may be due to several factors working in concert.

Animals↗
PubMed1997

Analysis of Trypanosoma brucei vsg expression site switching in vitro.

Trypanosoma brucei can undergo antigenic variation by switching between distinct telomeric variant surface glycoprotein gene (vsg) expression sites (ESs) or by replacing the active vsg. DNA rearrangements have often been associated with ES switching, but it is unclear if such rearrangements are necessary or whether ES inactivation always accompanies ES activation. To explore these issues, we derived ten independent clones, from the same parent, that had undergone a similar vsg activation event. This was achieved in the absence of an immune response, in vitro, using cells with selectable markers integrated into an ES. Nine of the ten clones had undergone ES switching. Such heritable changes in transcription state occurred at a frequency of approximately 6 x 10(-7). Comparison of switched and un-switched clones highlighted the dynamic nature of T. brucei telomeres, but changes in telomere length were not specifically associated with ES switching. Mapping within and beyond the ESs revealed no detectable DNA rearrangements, indicating that rearrangements are not necessary for ES activation/inactivation. Examination of individual cells indicated that ES activation consistently accompanied inactivation of the previously active ES. In some cases, however, we found cells that appeared to have efficiently established the switched state but which subsequently, at a frequency of approximately 2 x 10(-3), generated cells expressing both pre- and post-switch vsgs. These results show that ES activation/inactivation is usually a coupled process but that cells can inherit a propensity to uncouple these events.

Animals↗
PubMed1997

The role of inhibition in an associative memory model of the olfactory bulb.

The external plexiform layer is where the interactions between the mitral (excitatory) and granule (inhibitory) cells of the olfactory bulb (OB) take place. Two outstanding features of these interactions are that they are dendrodendritic and that there seem to be none between excitatory cells. The latter are usually credited with the role of forming Hebbian cell assemblies. Hence, it would seem that this structure lacks the necessary ingredients for an associative memory system. In this article we show that in spite of these two properties this system can serve as an associative memory. Our model incorporates the essential anatomical characteristics of the OB. The memories in our system, defined by Hebbian mitral assemblies, are activated via the interactions with the inhibitory granule cells. The nonlinearity is introduced in our model via a sigmoid function that describes neurotransmitter release in reciprocal dendrodendritic synapses. The capacity (maximal number of odors that can be memorized) depends on the sparseness of coding that is being used. For very low memory activities, the capacity grows as a fractional power of the number of neurons. We validate the theoretical results by numerical simulations. An interesting result of our model is that its capacity increases as a function of the ratio of inhibitory to excitatory populations. This may provide an explanation for the dominance of inhibitory cells in the olfactory bulb.

Memory↗