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Biomedical subjects

M Cheney

Publications and source records attributed to M Cheney.

At least 19 recordsLinked to original sources

A novel, biodegradable polymer conduit delivers neurotrophins and promotes nerve regeneration.

OBJECTIVE/HYPOTHESIS: A wide variety of substances have been shown to promote neuritic extension after nerve injury. An obstacle to achieving the maximal benefit from these substances has been the difficulty in effectively delivering the substances over a protracted time course that promotes maximal, directed growth. In this study the delivery of a growth-promoting substance through a biodegradable conduit, using materials originally designed for drug delivery applications, was hypothesized to promote more robust neural regeneration than through conduits lacking the substance. The objectives of this study were to create a growth factor-loaded biodegradable nerve guidance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance. MATERIALS/METHODS: Inosine, a purine analogue thought to promote axonal extension following neural injury, was loaded into cylindrical polymer foams composed of a polylactide-co-glycolide copolymer. First, in vitro extravasation of inosine was measured over a several week period using spectrophotometry. Second, the foams were fashioned into single-channel cylindrical nerve guidance conduits via a novel, low-pressure injection molding technique. The conduits were then used to bridge 7-mm defects in the rat sciatic nerve (n = 8). Control conduits lacking inosine were implanted into another set of animals as controls (n = 12). RESULTS: In vitro spectrophotometric measurements indicated appreciable leaching of inosine from the loaded foams over a period of at least 9 weeks. In the in vivo model, after 10 weeks, a higher percentage cross sectional area composed of neural tissue existed through the inosine-loaded conduits compared with controls (mean 44%, SD 7.5% vs. 36%, SD 8.6%, respectively). A difference was also found in mean fiber diameter between the two groups, with the inosine-loaded tubes showing a statistically significantly larger diameter than controls (P < .05). CONCLUSIONS: A nerve regeneration conduit was successfully created that delivers growth promoting substances over a protracted time course. In an in vivo model, the presence of inosine, a purine analogue, yielded neural regeneration whose histological features suggest possible superior long-term motor function.

Absorbable Implants↗

A tissue-engineered conduit for peripheral nerve repair.

BACKGROUND: Peripheral nerve repair using autograft material has several shortcomings, including donor site morbidity, inadequate return of function, and aberrant regeneration. Recently, peripheral nerve research has focused on the generation of synthetic nerve guidance conduits that might overcome these phenomena to improve regeneration. In our laboratory, we use the unique chemical and physical properties of synthetic polymers in conjunction with the biological properties of Schwann cells to create a superior prosthesis for the repair of multiply branched peripheral nerves, such as the facial nerve. OBJECTIVES: To create a polymeric facial nerve analog approximating the fascicular architecture of the extratemporal facial nerve, to introduce a population of Schwann cells into the analog, and to implant the prosthesis into an animal model for assessment of regeneration. RESULTS: Tubes of poly-L-lactic acid (molecular weight, 100000) or polylactic-co-glycolic acid copolymer were formed using a dip-molding technique. They were created containing 1, 2, 4, or 5 sublumina, or "fascicular analogs." Populations of Schwann cells were isolated, expanded in culture, and plated onto these polymer films, where they demonstrated excellent adherence to the polymer surfaces. Regeneration was demonstrated through several constructs. CONCLUSIONS: A tubular nerve guidance conduit possessing the macroarchitecture of a polyfascicular peripheral nerve was created. The establishment of resident Schwann cells onto poly-L-lactic acid and polylactic-co-glycolic acid surfaces was demonstrated, and the feasibility of in vivo regeneration through the conduit was shown. It is hypothesized that these tissue-engineered devices, composed of widely used biocompatible, biodegradable polymer materials and adherent Schwann cells, will be useful in promoting both more robust and more precisely directed peripheral nerve regeneration.

Animals↗

Postmarket surveillance to determine nutritional impact of macronutrient substitutes.

The nutritional impact of a macronutrient substitute can only be determined after the substitute has been approved for use in foods and there is widespread use by the population over time. Modeling and experimental studies have predictive value, but they cannot replace real life in which the choice of foods in influenced by labeling and advertising aimed at promoting consumption of the basis of reduced sugar, fat, and/or energy. Impacts could include alterations in the energy distribution of the diet and changes in the intakes of essential nutrients. For this reason, postmarket surveillance (PMS) of consumption patterns of macronutrient substitutes has been proposed as a condition of approval of macronutrient substitutes and/or extending permitted uses. PMS should be conducted on a representative sample of the population, should allow comparisons over time, and should collect data on food consumption patterns, nutrient intakes, and frequency of consumption of macronutrient substitutes. This is a more detailed and costly form of PMS than measuring actual product consumption.

Food, Formulated↗

A modified transfacial approach to the clivus.

Anterior approaches to the clivus must provide excellent visualization of the lesion, give adequate access for dural repair, and be cosmetically acceptable. Most current approaches enter through the nasopharynx or oropharynx, with either palatal, maxillary, or mandibular splitting for greater exposure. We have modified the transfacial approach described by others, which provides excellent access to the clivus along its rostrocaudal extent. A lateral rhinotomy incision is used and carried along the base of the right alae nasi and columella. The nasal bones are osteotomized bilaterally, and the nose is rotated on a pedicle flap, thus opening the entire nasal cavity to view. The septum and medial maxillary walls are removed. This provides excellent visualization of the ethmoid, sphenoid, posterior nasopharynx, and upper oropharynx. At the conclusion of the procedure, the nasal incision is closed, with good cosmesis. A case of recurrent chordoma of the middle and lower clivus is presented to exemplify this technique. The approach has since been used to approach clivus tumors and midline aneurysms of the vertebrobasilar system.

Brain Neoplasms↗

Botulinum A toxin for treatment of aberrant facial nerve regeneration.

Twelve patients with involuntary synkinetic eyelid closure were given 40 injections of botulinum A toxin. Temporary improvement in involuntary eyelid closure was observed in all 12 patients. Eleven of the 12 patients desired repeated injections. Dose requirements for this indication were compared with doses used in 697 injections in 112 patients with essential blepharospasm and Meige syndrome. Additionally, dose comparisons were made with 269 injections in 71 patients with hemifacial spasm. Dose requirements needed to treat aberrant regeneration of the facial nerve were substantially less than needed to treat blepharospasm and Meige syndrome. The dose requirement was similar to that in hemifacial spasm treatment. The reason for the differences probably relates to existing muscular denervation associated with hemifacial spasm and aberrant facial nerve regeneration.

Blepharospasm↗

Automatic and attentional priming in young and older adults: reevaluation of the two-process model.

Three experiments addressed the distinction between automatic and attentional mechanisms underlying semantic priming effects by factorially crossing prime-target relatedness, expectancy, and SOA in a task (pronunciation) that minimized postlexical checking processes. Also, possible age-related (young vs. older adults) differences in the automatic and attentional mechanisms were addressed. Across all experiments there was evidence of a Relatedness x Expectancy x SOA interaction, which is inconsistent with the notion of independent automatic and attentional mechanisms in semantic priming and the notion of a self-encapsulated modular lexicon. The results also indicated age-related differences in the build-up of the expectancy effect across SOAs when the prime was visually available for only 200 ms, independently of the prime-target SOA (Experiments 1 and 3), but not when the prime was visually available throughout the SOA (Experiment 2).

Adolescent↗

Distinguishability in impedance imaging.

Impedance imaging systems apply currents to the surface of a body, measure the induced voltages on the surface, and from this information, reconstruct an approximation to the electrical conductivity in the interior. This paper gives a detailed discussion of several ways to measure the ability of such a system to distinguish between two different conductivity distributions. The subtle differences between these related measures are discussed, and examples are provided to show that these different measures can give rise to different answers to various practical questions about system design.

Computer Simulation↗

Contralateral injections of botulinum A toxin for the treatment of hemifacial spasm to achieve increased facial symmetry.

Six patients noted facial asymmetry after botulinum toxin injection for hemifacial spasm. Each patient was injected on the side contralateral to the spasms with 10 to 15 IU over the zygomatic major and minor muscles. Each patient noted improvement in facial symmetry in the resting position and dynamic facial movements. Five of the six patients desired this approach with subsequent injections. This injection method variation proved helpful in the managing of hemifacial weakness created by botulinum A toxin for this condition.

Adult↗

Paired associate learning in senile dementia of the Alzheimer type.

A study was conducted to examine the potential explicit learning ability in senile dementia of the Alzheimer type (SDAT) as a function of (1) the difficulty of the to-be-remembered material and (2) the severity of the dementia. The Associate Learning task from the Wechsler Memory Scale was administered to healthy older adults and individuals with questionable, mild, and moderate SDAT. Individuals with SDAT showed poorer learning performance across trials than healthy older adults. Individuals with questionable and mild SDAT did show evidence for learning across trials for highly related paired associates. For unrelated-paired associates, however, only individuals with questionable SDAT showed some evidence for increased learning across trials.

Alzheimer Disease↗

Detection and imaging of electric conductivity and permittivity at low frequency.

This paper is concerned with low frequency electrical impedance imaging, which is the process of constructing images of the electrical impedance of a body's interior based upon measurements of voltage and current made at the body's surface. The electrical impedance accounts for both resistivity and permittivity. This paper shows how permittivity can be exploited to improve the performance of an electrical impedance imaging system. We show that explicit use of the independent information in the data due to the permittivity will ehance a system's ability to distinguish objects in the interior of a body. In addition, we report the results of experiments performed using the Rensselaer ACT 2 system on a saline bath containing various objects. These objects include both living tissue and metal conductors with oxide layers. We demonstrate the system's ability to distinguish these objects, and we exhibit gray scale images of both their resistivity and permittivity distributions.

Diagnostic Imaging↗

Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis.

Infection with reovirus 3 (Reo-3) has been suggested as the cause of extrahepatic biliary atresia and idiopathic neonatal hepatitis, but confirmation has been lacking. Therefore we have searched for a specific anti-Reo-3 antibody response in the sera of patients with biliary atresia or neonatal hepatitis and for Reo-3 antigens in their hepatobiliary tissues. Sera from 23 infants with extrahepatic biliary atresia, 12 with neonatal hepatitis, 30 age-matched control patients with other liver diseases, and 55 control patients without liver disease were tested by an enzyme-linked immunosorbent assay for total (IgA, IgG, and IgM) anti-Reo-3 antibodies; sera of infants younger than 6 months of age were tested also for IgM anti-Reo-3 antibodies alone. There was no difference between either total or IgM anti-Reo-3 antibody levels in infants with extrahepatic biliary atresia or neonatal hepatitis and levels in control infants. Reo-3 antigens were not detected in the hepatobiliary tissues of 19 infants (18 with biliary atresia, one with neonatal hepatitis) by an immunoperoxidase method that readily demonstrated Reo-3 in control infected HEp-G2 cells. Our data do not support a relationship between neonatal liver diseases and infection with Reo-3.

Antigens, Viral↗

Frequency and clinical progression of the vitamin E deficiency neurologic disorder in children with prolonged neonatal cholestasis.

To determine the frequency of biochemical vitamin E deficiency and of the clinical signs of the vitamin E deficiency neurologic syndrome in children with prolonged neonatal cholestatic disorders, we studied 46 children (aged 1 month to 17.0 years) with chronic forms of intrahepatic neonatal cholestasis and 47 children (aged 4 months to 8.0 years) with extrahepatic biliary atresia. Based on serum vitamin E concentrations and the ratios of serum vitamin E concentration to total serum lipid concentration, 64% of the intrahepatic and 77% of the extrahepatic cholestasis groups were vitamin E deficient. Prior to age 1 year, neurologic function was normal in all children. Between ages 1 and 3 years, neurologic abnormalities were present in approximately 50% of the vitamin E-deficient children; after age 3 years, neurologic abnormalities were present in all vitamin E-deficient children. Areflexia was the first abnormality to develop between ages 1 and 4 years; truncal and limb ataxia, peripheral neuropathy, and ophthalmoplegia developed between ages 3 and 6 years. Neurologic dysfunction progressed to a disabling combination of findings by ages 8 to 10 years in the majority of vitamin E-deficient children. Neurologic function was normal in the vitamin E-sufficient children. We conclude that vitamin E status should be evaluated in infants in whom cholestasis is diagnosed, and effective therapy should be initiated to prevent or treat vitamin E deficiency at an early age.

Adolescent↗