Biomedical subjects

R M Siegel

Publications and source records attributed to R M Siegel.

At least 19 recordsLinked to original sources

PubMed1997

Analysis of optic flow in the monkey parietal area 7a.

Environmentally relevant stimuli were used to examine the selectivity of area 7a neurons to optic flow using moving, flickering dots. Monkeys performed a psychophysical task requiring them to detect changes in translation, rotational and radially structured optic flow fields consisting of collections of moving dots which are free of form cues. The neurons in area 7a were selectively responsive to all the different types of moving stimuli. Two types of tuning for motion selectivity were found. Some neurons were tuned to distinguish a particular direction of optic flow (e.g. radial expansion versus radial compression), while others were tuned to distinguish between different classes of optic flow (e.g. radial motion versus planar rotation). The latter tuning was unlike that reported for area MST by others and may represent a novel representation of optic flow. The response of these neurons to translating bars was compared to that of optic flow fields. There appeared to be no similarity in the tuning to the two types of motion. Furthermore, there does not appear to be an identity between the neurons that could be classified as opponent vector and those selective for radial optic flow. Area 7a is involved in the further analysis of optic flow beyond the cortical areas MT and MST and provides a novel representation of motion. These results are consistent with the neurons in area 7a utilizing motion for the construction of a spatial representation of extra-personal space.

Animals↗

PubMed1996

The origins of aperiodicities in sensory neuron entrainment.

Aperiodic entrainment to rhythmic sensory input was obtained with either a single neuron or an excitatory network model, without addition of a stochastic or "noisy" element. The entrainment properties of primary sensory neurons were well captured by the dynamics of the Hodgkin-Huxley ordinary differential equations with a quiescent resting state or threshold for spike output. The frequency-amplitude parameter space was compressed and aperiodic regimes were small in comparison to those of periodically activated pacemaker-like neurons. Transitions between phase-locked and aperiodic entrainment patterns were predictable and determined by the equation dynamics, supporting the contention that some aperiodicities observed in situ arise from the inherent membrane properties of neurons. When the rhythmically activated neuron was embedded in an excitatory network of Hodgkin-Huxley neurons with heterogeneous synaptic delays, aperiodic entrainment patterns were more frequently encountered and these were associated with asynchronous output from the network. Embedding the rhythmically activated neuron in a network with synaptic delays greatly reduced the range of entrained spike frequencies and increased the variability in the neuronal firing. The temporal coding of sensory stimuli may be dependent on these findings. Sensory stimuli are signaled in the periphery by a mixture of periodic and irregular interspike intervals. Most models of such temporal codes assume intrinsic rhythmicity arising from the ionic currents, with variations attributed to membrane or synaptic noise. In contrast, we demonstrate irregular neural codes that arise completely in the absence of noise. In the proposed model, the sources of these irregular sensory patterns are the extensive cross-connections and resultant interactions between neurons. The balance between the regular and irregular entrainment of a neuron in situ could uniquely identify a stimulus. Other biological mechanisms of modifying the entrainment properties and promoting aperiodic entrainment are discussed.

Mathematics↗

PubMed1996

Physician beliefs and knowledge about vaccinations. Are Cincinnati doctors giving their best shot?

The purpose of this study was to examine the immunization beliefs and practices of physicians in our community. A two-page descriptive survey of immunization practices and knowledge of vaccine contraindications was sent to all community physicians on the staff of Children's Hospital Medical Center in Cincinnati, Ohio. More than 90% of practitioners used well-child visits for immunization, even if the child was ill. Although 83% of respondents correctly identified illness with fever as a false contraindication to immunization, only 25% (if the child is due for a visit) and 36% (if the child is overdue) would use ill visits to immunize if a child had fever. The chief concern over using ill visits for immunization was that children would not return for regular well visits. We conclude that greater efforts are needed to convince physicians that using ill visits to immunize children will not interfere with routine well care.

Adult↗

PubMed1995

The prevalence of sexually transmitted diseases in children and adolescents evaluated for sexual abuse in Cincinnati: rationale for limited STD testing in prepubertal girls.

OBJECTIVE: To determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, syphilis, and human immunodeficiency virus (HIV) infection in sexually abused children and to develop selective criteria for sexually transmitted disease (STD) testing in these children in our community. DESIGN: Prospective. SETTING: University-affiliated children's hospital in Ohio. PARTICIPANTS: All children evaluated at our hospital for sexual abuse were eligible. Eight hundred fifty-five children were evaluated over a 1-year period. The study included 704 girls and 151 boys. Children ranged in age from 3 weeks to 18 years old. METHODS AND RESULTS: Standard STD testing (American Academy of Pediatrics recommendations) was defined as serum rapid plasma reagin test, examination for Trichomonas, N gonorrhoeae culture of the throat, rectum, and genitalia and C trachomatis culture of the rectum and genitalia. STD testing in this study was recommended in children with 1) a history of genital discharge or contact with the perpetrator's genitalia, 2) examination findings of genital discharge or trauma, and 3) all adolescents. HIV testing was obtained in children with risk factors for HIV infection, those with contact with a perpetrator with HIV risk factors, or if the family was concerned about HIV acquisition. A total of 423 children were tested for N gonorrhoeae, 415 for C trachomatis, 275 for syphilis, 208 for Trichomonas, and 140 for HIV. Twelve children were determined to have N gonorrhoeae infection, 11 had C trachomatis infection, and four had Trichomonas infection. Overall, the prevalence of STDs in prepubertal girls was 3.2% and 14.6% in pubertal girls. The prevalence of N gonorrhoeae in prepubertal girls with vaginal discharge was 11.1% and 0% in prepubertal girls without discharge (P < .001). C trachomatis infection was diagnosed in 0.8% of prepubertal girls compared with 7.0% of pubertal girls (P < .001). None of the children tested positive for syphilis or HIV and no males had a STD. CONCLUSIONS: In our community, N gonorrhoeae testing in prepubertal girls can be limited to those with a vaginal discharge on examination unless other risk factors are present. The prevalence C trachomatis and Trichomonas in prepubertal girls is low and may be omitted from routine evaluations. All pubertal girls evaluated for sexual abuse should be tested for STDs because of the high prevalence of asymptomatic infection in this patient population.

Adolescent↗

PubMed1995

Humeral fractures without obvious etiologies in children less than 3 years of age: when is it abuse?

OBJECTIVE: To determine the occurrence and frequency of abuse in children with humeral fractures without immediately obvious etiologies who are less than 3 years old and present with arm injuries. METHODS: A retrospective chart review was conducted of all children less than 3 years old treated for a humeral fracture at Children's Hospital Medical Center between July 1, 1990, and September 10, 1993. One hundred twenty-four charts of children with humeral fractures were reviewed for possible abuse using previously developed criteria. Charts were evaluated independently by the investigators. Consensus was reached on classification of each chart into the following categories: abuse, indeterminate, or not abuse. RESULTS: Abuse was diagnosed in 9 of 25 (36%) children less than 15 months of age, but in only 1 of 99 (1%) children older than 15 months (P < .05). Abuse was excluded in 91 of 124 (73%) children. No determination of abuse (indeterminate) could be made in 23 of 124 (18.5%) children. In children less than 15 months of age, abuse was diagnosed in 2 of 10 (20%) with supracondylar fractures and in 7 of 12 (58%) with spiral/oblique fractures. CONCLUSION: The prevalence of abuse in our children presenting with humeral fractures was much lower than in other published reports, especially in the children over the age of 15 months. However, we found a higher prevalence of supracondylar fractures associated with abuse than those same reports. Given these findings, abuse should be considered in all children less than 15 months of age with humeral fractures, including those with supracondylar fractures. The majority of humeral fractures in children are accidental, especially beyond the age of 15 months.

Child Abuse↗

PubMed1994

The use of zinc protoporphyrin in screening young children for iron deficiency.

The common practice of screening children for iron deficiency with hematocrit (HCT) or hemoglobin detects only those children with iron deficiency severe enough to cause anemia. At 40 cents per test, zinc protoporphyrin (ZPP) can be measured in the physician's office and identify iron deficiency before anemia develops. The purpose of our study was to evaluate ZPP screening in young children by hematofluorimetry. All children between 9 and 36 months old were enrolled over a 1-year period. All children with HCT < 33% or iron deficiency (ZPP > or = 50 mumoles per mole-heme) were treated with ferrous sulfate at 3 mg-Fe/kg/day for 3 months. Four hundred and fifty-eight children were screened with a blood ZPP and spun HCT at entry. Two hundred and forty-three children (53%) had both a normal ZPP and HCT, 155 (34%) had a ZPP > or = 50 and normal HCT, 26 (6%) had a ZPP > or = 50 with HCT < 33%, and 34 (7%) had a normal ZPP and HCT < 33%. Of those with an elevated ZPP and normal HCT, 76% had a therapeutic response to iron therapy, with a 10% decrease in ZPP (P < 0.005). ZPP had a greater sensitivity (81%) than HCT (16%) in identifying children with iron deficiency. ZPP proved to be an effective and inexpensive addition to HCT in identifying children with iron deficiency.

Anemia, Iron-Deficiency↗

PubMed1994

Gld and lpr mice: single gene mutant models for failed self tolerance.

Mice homozygous for the gld or lpr mutations develop autoimmunity, and a lymphoproliferative disorder involving accumulation of huge numbers of unusual CD4-CD8-TCR alpha beta lo T cells. Here we review our past work with gld mice, and attempt to explain lymphoproliferation in terms of current models of T cell maturation and self-tolerance induction. The availability of molecular probes to the gene products of lpr and gld should shortly lead to a better understanding of the acquisition of self tolerance during T cell maturation and of autoimmunity.

Animals↗

PubMed1994

Hepatitis B vaccine use in Cincinnati: a community's response to the AAP recommendation of universal hepatitis B immunization.

The Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) recently recommended universal immunization of infants against hepatitis B virus (HBV). We surveyed all pediatricians and family practitioners with admitting privileges to our institution to determine their degree of approval of the AAP recommendation and the anticipated compliance with the recommendation. A questionnaire was sent to 86 family practitioners and 205 pediatricians; the response rate was 38% and 47%, respectively. The survey sought information regarding prior HBV immunization practices, planned HBV immunization strategies in the physician's office and hospital nursery, and the individual's opinion of the AAP recommendation. Only 21% of pediatricians and 12.5% of family practitioners anticipated giving HBV vaccine to all infants. An additional 22% of pediatricians and 28% of family practitioners planned to give HBV vaccine to infants who had the means to pay for the vaccine. Only a minority of physicians, 42.6% of pediatricians and 36.4% of family practitioners, approved of the AAP recommendation. We conclude that in our community there is widespread concern about the financial practicality and scientific merit of universal HBV immunization, and many practitioners will not comply with the AAP recommendation.

American Medical Association↗

PubMed1993

Temporal processing in the visual brain.

In conclusion these three results taken together--the single-unit data, the Gerstein and Mandelbrot model, and the modeled collection of neurons--suggest that the analysis of the temporal dynamics of neural systems can be furthered by the application of nonlinear dynamical theory. Furthermore, it appears that the range of temporal dynamics possible in visual cortex is quite broad, encompassing simple oscillations and more complex, perhaps chaotic, dynamics. Lastly, it appears that there are powerful principles at work that are leading to the organized behavior of a population of neurons. We suggest that these principles are constrained not only by the biological properties of the nervous system, but by profound mathematical principles that have already been described in many physical nonlinear systems under the aegis of chaos theory. If such constraints exist, we may have available to us mathematical and physical constructs that will allow us to study, model, and predict the behaviors of large collections of neurons that ultimately underlie the neural functioning of the brain.

Action Potentials↗

PubMed1993

Pattern recognition of the electroencephalogram by artificial neural networks.

A back-propagation network was trained to recognize high voltage spike-and-wave spindle (HVS) patterns in the rat, a rodent model of human petit mal epilepsy. The spontaneously occurring HVSs were examined in 137 rats of the Fisher 344 and Brown Norway strains and their F1, F2 and backcross hybrids. Neocortical EEG and movement of the rat were recorded for 12 night hours in each animal and analog data were filtered (low cut: 1 Hz; high cut: 50 Hz) and sampled at 100 Hz with 12 bit precision. A training data set was generated by manually marking durations of HVS epochs in 16 representative animals selected from each group. Training data were presented to back-propagation networks with variable numbers of input, hidden and output cells. The performance of different types of networks was first examined with the training samples and then the best configuration was tested on novel sets of the EEG data. FFT transformation of EEG significantly improved the pattern recognition ability of the network. With the most effective configuration (16 input; 19 hidden; 1 output cells) the summed squared error dropped by 80% as compared with that of the initial random weights. When testing the network with new patterns the manual and automatic evaluations were compared quantitatively. HVSs which were detected properly by the network reached 93-99% of the manually marked HVS patterns, while falsely detected events (non-HVS, artifacts) varied between 18% and 40%. These findings demonstrate the utility of back-propagation networks in automatic recognition of EEG patterns.

Animals↗

PubMed1993

Infant use of relative motion as information for form: evidence for spatiotemporal integration of complex motion displays.

Previous studies of infants' ability to integrate and to utilize relative motion as information for form in the absence of structural cues have primarily involved motions that are uniform in rate, direction, and path within the form to be constructed. In the present study, we examined infants' ability to integrate relative motion information from motions that are nonuniform along these dimensions, and from this integrative process to construct a coherently rotating two-dimensional form. Infants' ability to integrate nonuniform motion was measured with regard to their ability to discriminate the rotating form from a noncoherent control display containing the same absolute motions. The results showed that discrimination of the coherent and incoherent displays was not demonstrated until 7 months of age. Two additional experiments were conducted to rule out the possibility that this discrimination was based on the detection of local regions of coherence, rather than the perception of the global rotating form. In both experiments, the results did not support discrimination based exclusively on local cues alone. From the combined results of all three experiments, we conclude that infants demonstrate the capacity to integrate the information contained within nonuniform trajectories into a coherent structure by 7 months of age.

Age Factors↗

PubMed1992

Clinical success, complications and restenosis rates with excimer laser coronary angioplasty. The Percutaneous Excimer Laser Coronary Angioplasty Registry.

The role of excimer laser angioplasty in treating complex coronary artery disease remains uncertain. A randomized trial comparing this new technology with balloon angioplasty cannot be designed until systematic analysis identifies the lesion types that are likely to benefit from treatment with excimer laser angioplasty. In a cohort of 764 patients who had 858 coronary stenoses treated with excimer laser-facilitated angioplasty, relative risk analysis was used to examine acute success, complications and restenosis rates, and the results were compared with those of balloon angioplasty to identify the lesion types that show the greatest benefit with the new treatment. Clinical success was achieved in 657 patients (86%), as indicated by < or = 50% residual stenosis and no in-hospital complication. A major in-hospital complication (death, bypass surgery, or Q-wave or non-Q-wave myocardial infarction) occurred in 58 patients (7.6%). Follow-up angiography was obtained in 70% of eligible patients. Combining angiographic and noninvasive restenosis rates yielded an overall restenosis rate of 46%. Relative risk analysis showed that major complications occurred frequently in lesions at an arterial bifurcation (odds ratio [OR] 5.96 [2.76, 12.6]; p = 0.001). However, certain complex lesions that are difficult to treat with balloon angioplasty (saphenous vein graft lesions, lesions > 10 mm, ostial lesions, calcified stenoses, total occlusions and unsuccessful balloon dilatations), analyzed together as a group, had lower complication rates by univariate (OR 0.59 [0.35, 1.00]; p = 0.051) and multivariate logistic regression (p = 0.006) analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

PubMed1992

Differential effects of Bcl-2 on T and B cells in transgenic mice.

We have produced bcl-2 transgenic mice by using a construct which mimics the t(14;18) translocation in human follicular lymphomas. Although lymphoid tissues from all transgenic mice contained high levels of human Bcl-2 protein, transgene expression was differentially regulated within the B- and T-cell compartments of lines derived from various founder mice. We have characterized the phenotypes of two lines of bcl-2 transgenic mice (line 2 and line 6) in which bcl-2 transgene expression was restricted primarily to the T- or B-cell lineages, respectively. Analysis of line 6 lymphocytes revealed a polyclonal expansion of B cells, and these B cells exhibited prolonged survival in vitro. In line 2 mice, numbers of T cells in the peripheral lymphoid tissues were more moderately elevated despite enhanced T-cell survival in vitro. Line 2 transgenic mice also showed significantly increased proportions of thymocytes with a mature phenotype. Taken together, these findings suggest different roles for bcl-2 in the in vivo regulation of B- and T-cell development and homeostasis.

Animals↗

PubMed1992

Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice.

The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process.

Animals↗

PubMed1991

High-resolution optical imaging of functional brain architecture in the awake monkey.

Optical imaging of the functional architecture of cortex, based on intrinsic signals, is a useful tool for the study of the development, organization, and function of the living mammalian brain. This relatively noninvasive technique is based on small activity-dependent changes of the optical properties of cortex. Thus far, functional imaging has been performed only on anesthetized animals. Here we establish that this technique is also suitable for exploring the brain of awake behaving primates. We designed a chronic sealed chamber and mounted it on the skull of a cynomolgus monkey (Macaca fascicularis) over the primary visual cortex to permit imaging through a transparent glass window. Restriction of head position alone was sufficient to eliminate movement noise in awake monkey imaging experiments. High-resolution imaging of the ocular dominance columns and the cytochrome oxidase blobs was achieved simply by taking pictures of the exposed cortex when the awake monkey was viewing video movies alternatively with each eye. Furthermore, the functional maps could be obtained without synchronization of the data acquisition to the animal's respiration and the electrocardiogram. The wavelength dependency and time course of the intrinsic signal were similar in anesthetized and awake monkeys, indicating that the signal sources were the same. We therefore conclude that optical imaging is well suited for exploring functional organization related to higher cognitive brain functions of the primate as well as providing a diagnostic tool for delineating functional cortical borders and assessing proper functions of human patients during neurosurgery.

Animals↗

PubMed1991

Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients.

Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis.

Angioplasty, Laser↗

PubMed1990

Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule.

The anatomical and functional organization of the inferior parietal lobule was investigated in macaque monkeys by using anterograde and retrograde anatomical tracing techniques and single cell recording techniques in awake, behaving monkeys. The connections of areas 7a and 7b, and of two previously unexplored areas, the lateral intraparietal area (LIP) and the dorsal prelunate area (DP), were examined in detail. Functional mapping experiments were performed in all four areas. Prior to this study the pathways for visual input to area 7a were unclear. In these experiments we found several direct projections from extrastriate visual areas, including the lateral intraparietal (LIP), dorsal prelunate (DP), parieto-occipital (PO), and medial superior temporal (MST) areas into area 7a. Using the observed laminar patterns of connections between areas 7a, LIP, and DP and other extrastriate cortical areas, we were able to construct a hypothetical flow of visual information processing from striate cortex to area 7a. A broader hierarchy was also produced, which relates the positions of areas 7a, 7b, LIP, and DP to various cortical fields in the parietal, temporal, and frontal lobes. By combining single cell recording techniques in trained monkeys with anatomical tracing techniques, we have parceled the inferior parietal lobule into several subdivisions on the basis of both anatomical and physiological grounds. A clear segregation of visual and somatosensory responses was found in the inferior parietal lobule with areas 7a, LIP, and DP being visual and visual-motor and area 7b being primarily somatosensory. A similar segregation was found anatomically with areas 7a, LIP, and DP being interconnected primarily with other visual cortical areas and area 7b being connected with several somatosensory areas. Area 7b was also found to connect to a few visual cortical areas, and these connections likely account for the small but consistent number of visually responsive cells that are found in this region. Areas LIP, DP, and 7a differed in receptive field and saccade-related properties. Area 7a visual receptive fields were very large and usually bilateral with a small but significant number of them having receptive field centers in the ipsilateral visual field. Area DP and LIP receptive fields were smaller and the receptive field peaks were almost always confined to the contralateral visual field. Areas 7a, DP, and LIP all contained cells with saccade-related responses; however, in area 7a there were fewer saccade cells than area LIP, and presaccadic responses were only observed in area LIP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Origin and selection of peripheral CD4-CD8- T cells bearing alpha/beta T cell antigen receptors in autoimmune gld mice.

We have analyzed the origin and development of unusual CD4-CD8- alpha/beta T cell receptor-positive peripheral T cells produced in large numbers by mice homozygous for the gld mutation (C3H-gld/gld). These mice may be an important model for investigating processes controlling T cell development. Bone marrow transfers demonstrated that the gld defect was intrinsic to bone marrow-derived cells. Clonal deletion of potentially autoreactive cells was observed in peripheral gld CD4-CD8-, CD4+CD8-, and CD4-CD8+ T cells, as well as mature thymocytes. This suggests that gld CD4-CD8- T cells have passed through the thymus in ontogeny and that gld autoimmunity does not result from a general defect in elimination of self-reactive thymocytes. These observations, combined with demethylation of the CD8 gene in the CD4-CD8- population, support prior expression of CD4 and/or CD8 in gld CD4-CD8- T cell ontogeny, perhaps at a CD4+CD8+ stage. Steroid sensitivity of gld thymocytes and CD4-CD8- T cells was normal. Therefore, we found no gross abnormalities in two major mechanisms of inducible cell death in the gld thymus, the clonal deletion process associated with tolerance and the steroid-inducible endogenous endonuclease thought to be involved in apoptosis of unselected thymocytes. The data suggest that if gld CD4-CD8- T cells arise via escape from normal elimination in the thymus, they must do so by a novel defect in thymic selection (perhaps related to aberrant positive signals) and/or are expanded by an extrathymic process which allows clonal deletion to occur.

Animals↗