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Biomedical subjects

A M Schneider

Publications and source records attributed to A M Schneider.

At least 19 recordsLinked to original sources

Induction of pulmonary allergen-specific IgA responses or airway hyperresponsiveness in the absence of allergic lung disease following sensitization with limiting doses of ovalbumin-alum.

Respiratory allergies represent a failure to generate nonpathogenic responses to innocuous foreign materials. Herein we assessed the role of the sensitizing dose of allergen in this response/nonresponse paradigm, sensitizing BALB/c mice with 5 ng-2 microg of OVA-alum and assessing their responses to repeated OVA aerosol challenge. Mice sensitized with < or = 25 ng of OVA-alum did not develop atopic antibodies, airway hyperresponsiveness (AHR), eosinophilia, or pulmonary Th2 responses, but the 25-ng group animals did develop significant IgA responses. The mice sensitized with 100 ng of OVA-alum developed AHR in the absence of detectable allergic disease, while the mice sensitized with 250 ng-2 microg of OVA/alum developed full-spectrum allergic disease (i.e., eosinophilia, IgE, IgG1, pulmonary Th2 cytokine responses, and AHR). These data indicate that limiting doses of allergen can differentially induce IgA or AHR in the absence of atopic disease in mice.

Allergens↗

Ethanol inhibits spontaneous activity of central nucleus of the amygdala neurons but does not impair retention in the passive-avoidance task.

BACKGROUND: Behavioral studies using pharmacological manipulations that increase neuronal activity of the central nucleus of the amygdala (CeA) have implicated the CeA in enhancement of memory modulation. To date, however, there has been a dearth of studies investigating the effect of a drug that decreases CeA activity on memory modulation-a drug that inhibits the neuronal activity of the CeA might be expected to impair memory modulation. To determine whether ethanol inhibits CeA activity and, if so, whether decreased CeA activity is associated with impairment of memory modulation, this study investigated the effect of ethanol on spontaneous single-unit activity of CeA neurons and retention in the passive-avoidance task. METHODS: The effect of ethanol (0.35, 0.75, 1.5, 2.5 g/kg) was determined on spontaneously firing neurons in the CeA in urethane-anesthetized rats by use of standard in vivo single-unit electrophysiological recording techniques. Additionally, the effect of ethanol when administered immediately after training in a standard passive-avoidance task was determined on retention the following day. RESULTS: Ethanol profoundly inhibited spontaneous CeA firing rates in urethane-anesthetized rats at all doses tested. Maximal inhibition was related to dose. Each dose of ethanol significantly inhibited CeA activity within 15 min of administration; within 35 min of administration, 0.75 g/kg of ethanol inhibited CeA activity by 65.2%, and the highest dose (2.5 g/kg) produced nearly complete suppression of CeA activity (81.3%). Although ethanol markedly inhibited CeA activity, these same doses of ethanol failed to impair retention in the passive-avoidance task: 0.35, 0.75, 1.5, and 2.5 g/kg of ethanol, administered immediately after training, failed to alter latency to step-through the following day. CONCLUSIONS: These results show that ethanol profoundly inhibits spontaneous CeA activity and suggest that inhibition of the CeA is not sufficient to impair retention in the passive-avoidance task.

Amygdala↗

Lead hydro sodalite [Pb2(OH)(H2O)3]2[Al3Si3O12]2: synthesis and structure determination by combining X-ray rietveld refinement, 1H MAS NMR FTIR and XANES spectroscopy.

Ion exchange of the sodium hydro sodalites [Na3(H2O)4]2-[Al3Si3O12]2 [Na4(H3O2)]2[Al3Si3O12]2 and [Na4(OH)]2[Al3Si3O12]2 with aqueous Pb(NO3)2 solutions yielded, whichever reactant sodalite phase was used, the same lead hydro sodalite, [Pb2(OH)-(H2O)3]2[Al3Si3O12]2. Thus, in the case of the non-basic reactant [Na3(H2O)4]2-[Al3Si3O12]2 an overexchange occurs with respect to the number of nonframework cationic charges. Rietveld structure refinement of the lead hydro sodalite based on powder X-ray diffraction data (cubic, a = 9.070 A, room temperature, space group P43n) revealed that the two lead cations within each polyhedral sodalite cage form an orientationally disordered dinuclear [Pb2(micro-OH)(micro-H2O)(H2O)2]3+ complex. Due to additional lead framework oxygen bonds the coordination environment of each metal cation (CN 3+3) is approximately spherical, and clearly the lead 6s electron lone pair is stereochemically inactive. This is also suggested by the absence of a small peak at 13.025 keV, attributed in other Pb2+-O compounds to an electronic 2p-6s transition, in the PbL3 edge XANES spectrum. 1H MAS NMR and FTIR spectra show that the hydrogen atoms of the aqua hydroxo complex (which could not be determined in the Rietveld analysis) are involved in hydrogen bonds of various strengths.

Journal Article↗

Use of specialized bone screws for intermaxillary fixation.

Fixation of the injured mandible to the maxilla is a proven method of stabilizing mandibular fractures and ensuring proper occlusion. The authors report their results with new specialized intraoral bone screws (IMF Screw System; Howmedica Leibinger, Inc., Carrollton, TX) that are designed for the purpose of achieving intermaxillary fixation (IMF). Nineteen patients were placed into rigid IMF using IMF screws alone. Indications were nondisplaced mandibular fractures; symphyseal, body, and angle fractures; midfacial fractures requiring temporary IMF; and edentulous patients with any of these fracture types and an adequate prosthesis. All procedures were performed with the patient under general anesthesia. The authors found that the operative time was markedly shorter than with standard IMF techniques, patient satisfaction was high, and there were no infections related to the screws. All 19 patients remained in stable, accurate occlusion and had adequate healing. One patient continues to have paraesthesias in the mental nerve distribution after screw removal. Although there is the potential for tooth and nerve injury when screws are placed improperly, the IMF Screw System seems to be a safe and reliable method of achieving secure mandibular fixation.

Bone Screws↗

Provocative angiography in patients with gastrointestinal hemorrhage of obscure origin.

OBJECTIVE: A standard diagnostic evaluation including upper and/or lower endoscopy, tagged red blood cell scintigraphy, and visceral angiography identifies the source of GI bleeding in the majority of patients who present with acute GI hemorrhage. However, in a small group of patients the source of bleeding remains obscure; this form of GI hemorrhage is uncommon but represents a considerable diagnostic challenge. Some investigators have advocated provocation of bleeding with vasodilators, anticoagulants, and/or thrombolytics in association with tagged red blood cell scans or angiography. Unfortunately, the available literature on this topic is limited. Therefore, the purpose of this study is to report our experience with provocative GI bleeding studies. METHODS: The radiology databases at Duke University Medical Center and the Durham Veterans Administration Medical Center were reviewed from 1994 to 1999. Any patient who received a vasodilator, anticoagulant, or thrombolytic to induce bleeding during a tagged red blood cell scan or visceral angiogram was included. RESULTS: Seven provocative bleeding studies were performed on seven patients. All patients underwent a visceral angiogram with intra-arterial administration of tolazoline (a vasodilator), heparin (an anticoagulant), and/or urokinase (a thrombolytic). Of the seven provocative studies, only two induced angiographically identifiable bleeding. Both of these patients underwent surgical therapy. There were no complications attributed to the provocative bleeding studies. CONCLUSIONS: These results suggest that provocative GI bleeding studies can be performed safely. However, because an active bleeding source was identified in only a small proportion of patients, we believe that further study is required to optimize patient selection and to clarify the cost-effectiveness of this approach in patients with GI hemorrhage of obscure origin.

Adult↗

Beta-adrenergic receptor blockade by propranolol enhances retention in a multitrial passive-avoidance procedure.

The effect of beta-adrenergic receptor blockade on retention in a mildly aversive passive-avoidance procedure was investigated. Rats were given passive-avoidance training--1 trial per day for 4 days-and were administered saline, the centrally and peripherally acting beta-adrenergic blocker propranolol (4 or 10 mg/kg ip), or the peripherally acting beta-adrenergic blocker sotalol (4 or 10 mg/kg ip) immediately or 2 hr after the 1st trial. Enhanced retention occurred only with the higher dose (10 mg/kg) of propranolol and only when it was administered immediately after training. The enhanced retention produced by propranolol is discussed in terms of opposing, regionally specific actions of beta-adrenergic receptor-mediated neural circuits on modulation of memory.

Adrenergic beta-Antagonists↗

N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities.

We showed previously that the induction of neural crest (NC) and neural tube (NT) defects is a general property of N-methyl-D-aspartate receptor (NMDAR) antagonists. Since homocysteine induces NC and NT defects and can also act as an NMDAR antagonist, we hypothesized that the mechanism of homocysteine-induced developmental defects is mediated by competitive inhibition of the NMDAR by homocysteine. If this hypothesis is correct, homocysteine-induced defects will be reduced by NMDAR agonists. To test the hypothesis, we treated chicken embryos during the process of neural tube closure with sufficient homocysteine thiolactone to induce NC and NT defects in approximately 40% of survivors or with homocysteine thiolactone in combination with each of a selected set of NMDAR agonists in 0. 05-5000 nmol doses. Glutamate site agonists selected were L-glutamate and N-methyl-D-aspartate. Glycine site agonists were glycine, D-cycloserine, and aminocyclopropane-carboxylic acid. Glycine was the most effective overall, reducing defects significantly at two different doses (each P>0.001). These results support the hypothesis that homocysteine may affect NC and NT development by its ability to inhibit the NMDAR. One potentially important consequence of this putative mechanism is that homocysteine may interact synergistically with other NMDAR antagonists to enhance its effect on development.

Animals↗

A controlled subatmospheric pressure dressing increases the rate of skin graft donor site reepithelialization.

The ability to increase the rate of skin graft donor site reepithelialization significantly in a cost-effective manner has important implications for the patient undergoing major reconstructive procedures. In this study the effect of externally applied reduced pressure (the V.A.C.) on the rate of healing of donor site wounds was initially investigated using a porcine model (N = 4), then repeated on humans (N = 10). Split-thickness skin grafts were harvested from the backs of pigs using standard technique. Half of the donor sites were treated with subatmospheric pressure (125 mmHg) and half were treated with an OpSite dressing. Biopsies taken every 48 hours demonstrated that sites exposed to reduced pressure healed at a much faster rate than sites treated with a standard occlusive dressing. Similarly, donor sites in humans reepithelialized faster in 7 of 10 patients, the rate was the same in 2 of 10 patients, and OpSite was faster in 1 of 10 patients. We believe this technology has the potential to be a relatively simple and cost-efficient method for increasing the rate of donor site healing.

Adult↗

Iodine-131-metaiodobenzylguanidine uptake in metastatic carcinoid tumor to the orbit.

Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1%-13% of all orbital masses (1). In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit followed by metastases from the lung, prostate and gastrointestinal tract (2). It is rare for carcinoid tumors to metastasize to the eye or to the orbit. Carcinoid tumors arise from Kulchitsky cells that originate in the neural crest. Histologically, these tumors resemble, but are not as aggressive as, adenocarcinomas. Most carcinoids arise in the gastrointestinal tract or the lung. The most common site for carcinoid metastases is the liver. On anatomical imaging studies, such as CT and magnetic resonance imaging, metastatic orbital carcinoid tumors appear as nonspecific tumor masses. Carcinoid tumors have an affinity for uptake of the radiopharmaceutical 131I-metaiodobenzylguanidine (MIBG) (3). We report a case of a patient with a known carcinoid tumor who developed a left orbital mass that demonstrated abnormal uptake of 131I-MIBG indicative of metastatic carcinoid tumor to the orbit.

3-Iodobenzylguanidine↗

Elecsys CEA, PSA and AFP. Clinical results of a multicentre evaluation.

Three tumormarker assays, Elecsys CEA, PSA and AFP, have been evaluated in an international multicentre study to characterize their clinical performance and to verify the comparability with the corresponding tests of the Enzymun-Test product line and other methods. For each of the markers results were obtained from four laboratories. On the basis of 314 and 199 specimens respectively, (preliminary) reference ranges could be established for CEA and PSA. For the prostate marker, the age dependence of the antigen level could be clearly confirmed. Mean concentrations range between 0.51 ng/ml (< 40 years) and 3.57 ng/ml (> 70 years). Referring to CEA, 95th percentiles of 4.31 ng/ml and 2.69 ng/ml were elaborated for smokers and nonsmokers. In general, good to excellent correlations (r > 0.98) were found between the Elecsys and Enzymun-Tests. Regarding the systematic comparability of both systems, most of the slopes derived from the individual method comparison studies are within the +/- 10% range of the respective standardization results. The specific distribution pattern of the individual tumormarker values elaborated with sample material of known clinical background, reflects the well established categorization of different benign and malignant diseases according to their characteristic marker levels. Of utmost importance, however, is the excellent comparability of the Elecsys assays with the corresponding Enzymun-Tests and the FDA approved AIA 1200 tests from TOSOH in follow-up studies. Almost superimposable concentration curves guarantee that identical diagnostic information is derived from all three methods. Especially for PSA, a series of measurements on sera of prostatectomized patients proved the usability and clinical value of the test also for this particular indication. For either one of the Elecsys tests, the feasibility of using plasma as sample material was verified.

Adult↗

Metastatic head and neck cancer to the percutaneous endoscopic gastrostomy exit site: a case report and review of the literature.

Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure and is an important supportive treatment adjunct for patients with head and neck cancer. We report a case in which squamous cell carcinoma of the larynx implanted at a PEG exit site. This was resected for cure. In this case, and in five others reviewed in the literature, the PEG placement method was the "pull" technique. It is unknown whether other methods of PEG placement may reduce metastatic implants at the PEG exit site, but the possibility of this complication must be considered.

Carcinoma, Squamous Cell↗

Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein.

Mutations in genes encoding membrane proteins have been associated with cell death of unknown cause from invertebrate development to human degenerative diseases. A point mutation in the gene for myelin proteolipid protein (PLP) underlies oligodendrocyte death and dysmyelination in jimpy mice, an accurate model for Pelizaeus-Merzbacher disease. To distinguish the loss of PLP function from other effects of the misfolded protein, we took advantage of the X chromosomal linkage of the gene and have complemented jimpy with a wild-type PLP transgene. In this artificial heterozygous situation, the jimpy mutation emerged as genetically dominant. At the cellular level oligodendrocytes showed little increase in survival although endogenous PLP gene and autosomal transgene were truly coexpressed. In surviving oligodendrocytes, wild-type PLP was functional and immunodetectable in myelin. Moreover, compacted myelin sheaths regained their normal periodicity. This strongly suggests that, despite the presence of functional wild-type PLP, misfolded jimpy PLP is by itself the primary cause of abnormal oligodendrocyte death.

Animals↗

Predictors of behavior problems in three-year-old sons of alcoholics: early evidence for the onset of risk.

We investigated risk factors in a population-based sample of alcoholic (father) and comparison families with 3-year-old sons. Alcoholic and comparison parents did not differ in socioeconomic status (SES), education, years married, family size, or cognitive functioning. Antisocial behavior and depression were significantly greater in alcoholic parents. High risk children were more impulsive than comparison children, but there were no differences in developmental age, IQ, or behavior problems. A higher percentage of high-risk children were rated in the extreme clinical range for behavior problems than were comparison children. For alcoholic families, mothers' ratings of their children's total behavior problems, externalizing behavior problems, and internalizing behavior problems were predicted by mothers' lifetime alcohol problems, current depression, and family SES. Father variables failed to predict children's behavior problems. Maternal variables were stronger predictors of their 3-year-old sons' problem behaviors than were paternal variables.

Achievement↗

Improved safety and efficacy in adaptive control of arterial blood pressure through the use of a supervisor.

This paper presents a dual approach to adaptive control of arterial blood pressure using sodium nitroprusside. In the clinical environment, a controller must be aggressive to achieve specific step response characteristics (less than 10 min settling time, less than 10 mm Hg overshoot), yet conservative enough to prevent overreactions to large disturbances, which are common in both the operating room and the intensive care unit. These mutually exclusive requirements make it difficult to design a closed-loop controller for this environment. To prevent possible overreactions, while maintaining proper step response, an aggressive adaptive controller has been designed to achieve the desired step response, and a SUPERVISOR has been designed around the adaptive controller to limit potential overreactions in the presence of disturbances. Simulations and dog experiments demonstrate the potential for increased safety and efficacy using this dual approach to the control of a complex physiological system.

Animals↗

Supervisory adaptive control of arterial pressure during cardiac surgery.

A supervisory adaptive controller has been designed for the closed-loop control of mean arterial pressure during cardiac surgery, using sodium nitroprusside. This controller consists of a pole-placement and proportional-plus-integral feedback regulator, multiple-model adaptation, and a supervisor. The pole-placement and proportional-plus-integral regulator was designed to meet aggressive step response characteristics. Multiple-model adaptation was chosen to ensure rapid and stable adjustments for changes in key patients parameters. The supervisor was designed to provide safety and efficacy of control during disturbances that are common during cardiac surgery. We studied the ability of this supervisory adaptive controller to regulate arterial pressure during cardiac surgery on nineteen patients. The controller, through the action of the supervisor, detected and responded appropriately to the great majority of disturbances. This study demonstrated that supervisory adaptive control has the potential to provide clinically acceptable regulation of arterial pressure.

Cardiac Surgical Procedures↗

Neutrophil short-lived oxidant production: enhancement following onset of sepsis-induced lung injury.

Generation of superoxide anion (O2-) by activated neutrophils (PMN) is implicated in the pathogenesis of endothelial cell injury in sepsis. To quantitate this phenomenon we studied the kinetics of O2- production by PMN following in vivo and in vitro exposure to Pseudomonas aeruginosa. PMN were isolated from young swine before and after a 1-hr infusion with 5 x 10(8) organisms/ml at 0.3 ml/20 kg/min. Baseline PMN were studied in an in vitro system where 1 x 10(6) porcine PMN were incubated with live Pseudomonas for 1 hr at 37 degrees C. Neutrophils from septic pigs exhibited a significantly increased (P less than 0.05) initial rate of O2 production, which was 125% greater at 2 min following initial stimulation than saline controls (P less than 0.001). Neutrophils exposed in vitro displayed a similar enhancement of the rate of O2- production; however, the rate was 3.6 times greater than that noted in vivo. The in vivo change in PMN oxidant generation was associated with a rise in both extravascular lung water (EVLW) and increased bronchoalveolar lavage protein (BAL-P) content. These data suggest that sepsis-induced acute lung injury is accompanied by "priming" of circulating PMN; however, important factors are present in the circulation in sepsis that serve to attenuate the damaging potential of PMN oxidant species.

Animals↗