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Biomedical subjects

M E Michel

Publications and source records attributed to M E Michel.

At least 19 recordsLinked to original sources

Workshop on intraspinal transplantation and clinical application.

The following general conclusions were reached at the workshop: 1. Laboratory studies suggest a potential benefit of cellular transplant therapy for SCI. 2. Some evidence supporting the safety of human fetal transplants is available from clinical studies of transplants in Parkinson's disease and SCI. 3. Assessment criteria and methodology are available, including imaging approaches, validated neurologic scoring systems, detailed electrophysiologic studies of conduction and spinal cord reflexes, and functional scoring approaches. 4. More controlled animal studies are needed (a) to demonstrate efficacy and to evaluate the necessity for immunosuppressive therapy and the overall safety of intraspinal transplantation, (b) to obtain more supporting evidence (e.g., electrophysiologic, histopathologic, MRI, molecular) that would provide insights into ways that transplanted tissue could mediate function, (c) to provide guidance for the procurement, harvesting, preparation, storage, and other logistics related to the use of human cells for transplantation into the spinal cord, (d) to define more thoroughly the cell type(s) that would be most likely to have benefit and the conditions that affect their viability, migration, gene expressions, and proliferation after transplantation, (e) to determine the most optimal time after injury for transplantation, and (f) to clarify patient selection characteristics that might optimize success (i.e., complete vs incomplete injuries, spinal level involved, age of recipient).

Animals↗

Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference.

A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing.

Adolescent↗

[Not Available].

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Academies and Institutes↗

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Exhibitions as Topic↗

Regional brain glucose uptake in genetically diabetic C57BL/KsJ mice: modulation by the opiate antagonist, nalmefene.

A novel opiate antagonist, Nalmefene (0.5 or 5.0 mg/kg/day) was tested for its ability to modulate regional brain glucose uptake rates in genetically diabetic C57BL/KsJ mice, which normally exhibit a depressed CNS carbohydrate metabolism relative to age-matched controls. Daily Nalmefene treatment had no effect on circulating blood glucose levels in either normal or diabetic mice over a 7-week test period. However, all brain regions, except the olfactory bulbs, exhibited normalized glucose uptake rates in diabetic mice relative to controls. These data suggest a role for opiate antagonists in the modulation of CNS glucose metabolism during hyperglycemic states.

Animals↗

[Not Available].

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France↗

[Not Available].

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France↗

The effect of alcohol on nocturnal gastroesophageal reflux.

The effect of 120 mL (4 oz) of scotch whiskey (40% alcohol) on nocturnal gastroesophageal reflux was studied by ambulatory esophageal pH monitoring. Seventeen healthy volunteers were studied on two occasions, using a computerized radiotelemetric esophageal pH monitoring system. The subjects were given the alcohol during the second session, three hours after the evening meal, and went to bed at their usual time. Seven of the 17 subjects had prolonged supine reflux episodes on the night of alcohol ingestion. These lasted an average of 47.1 minutes (23.2 to 91.8 minutes) and occurred on an average of 3 1/2 hours after ingestion of whiskey and 1.4 hours after lying down. None of the subjects had these episodes on the control night. There was also a significant acidic shift in the cumulative percentage of data points below a pH of 3 and a pH of 4 in the supine position on the night of alcohol ingestion compared with the control night. This study has shown that there was a significant exposure of the distal esophagus to acid and that the normal acid clearance of the esophagus in the supine position was impaired after only moderate amounts of alcohol.

Adult↗

Peripheral nerve as an osmometer: role of endoneurial capillaries in frog sciatic nerve.

The sciatic nerve of the frog was perfused in vivo with isotonic Ringer solution followed by Ringer made hypertonic by addition of sucrose or of NaCl. Nerve diameter and endoneurial hydrostatic pressure fell during hypertonic Ringer perfusion. Using a model that describes the elastic and osmotic properties of the nerve, sigma sLp, the product of the osmotic reflection coefficient at endoneurial capillaries for s equals sucrose or NaCl (which approximates 1), and of capillary hydraulic conductivity, was found to equal 73 X 10(-13) cm3 X s-1 X dyn-1. The nerve is elastic. It has a compliance K of 3.7 X 10(-5) cm2 X mmHg-1, corresponding to a modulus of elasticity E of the perineurium equal to 1.2 X 10(6) dyn X cm-2. The results indicate that the nerve behaves as an osmometer during vascular perfusion, due to the low permeability of endoneurial capillaries to small solutes such as NaCl and sucrose. A low capillary hydraulic conductivity limits bulk water flow between blood and nerve, and a low compliance limits nerve swelling and edema.

Animals↗

[Not Available].

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France↗

Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones.

Condensation products of beta-cyclodextrin with propylene oxide or epichlorohydrin, which are amorphous and thus very soluble in water, were used to form complexes with testosterone, progesterone, and estradiol. Sublingual/buccal administration of tablets of these complexes led to effective absorption and entry of the hormones into the systemic circulation, followed by gradual elimination; rapid first-pass loss was avoided. beta-Cyclodextrin itself, its 2,6-dimethyl derivative, and a nonionic detergent did not enable effective buccal absorption. Absorption from the GI tract of hormones complexed with hydrophilic cyclodextrins was also less effective. Effective absorption of drugs from the oral cavity requires (a) that the drug and solubilizer form a complex of the inclusion type which dissolves completely and rapidly and (b) that the solubilizer neither enters nor damages oral tissue.

Administration, Oral↗

Influence of nalmefene on energy balance and glucose regulation in Zucker rats.

It has been hypothesized that opioid peptides play a role in the development of obesity. The opiate antagonist naltrexone decreases glucose-stimulated insulin release, while the sensitivity of diabetic rats to naloxone-induced satiety is increased. These findings suggest a possible interaction between glucose concentrations and opiate antagonists in the control of food intake. In three experiments the energy balance and glucose regulatory responses of Zucker obese and lean rats to chronic administration of nalmefene, an opiate antagonist, were measured. Nalmefene, when injected subcutaneously or added to feed for 21 days, decreased food intake and weight gain of obese and lean rats. These responses were more pronounced during the first week of treatment and were greater in obese than lean rats. Nalmefene increased glucose concentrations during day 1 and weeks 1, 2 and 3 only when given subcutaneously. Nalmefene given intragestrically attenuated glucose-stimulated increases in insulin release only in obese rats. Thus, chronic nalmefene administration is not likely to be an effective treatment for obesity or diabetes.

Administration, Oral↗

Sciatic nerve blood flow measured by laser Doppler flowmetry and [14C]iodoantipyrine.

Blood flow was examined in sciatic nerves of pentobarbital-anesthetized rats by means of laser Doppler flowmetry (LDF) and intravenous [14C]iodoantipyrine infusion. Continuous LDF signals demonstrated slow oscillations and acute, pressure-related changes in flow. The steady-state LDF signal was related linearly to nerve blood flow, as measured with [14C]iodoantipyrine, in intact nerves and nerves stripped of the epineurium. In 14 intact nerves, nerve blood flow averaged 0.27 +/- 0.03 (SE) ml X min-1 X g-1, whereas it averaged 0.13 +/- 0.01 in 5 stripped nerves. Autoradiographs of [3H]-nicotine-infused nerves and intra-arterial injection of 57Co-labeled microspheres demonstrated that flow was not uniform throughout the nerve cross section. The results indicate that LDF can be used to examine nerve blood flow in vivo, demonstrate a linear relation between the LDF signal and flow, and establish absolute values for blood flow in intact and stripped nerves of the anesthetized rat.

Animals↗

Binding of a new opiate antagonist, nalmefene, to rat brain membranes.

Nalmefene (6-methylene-naltrexone) is a potent, orally active, opiate antagonist. IC50's were obtained for nalmefene, naloxone and naltrexone using radiolabelled prototype ligands for mu, kappa and delta receptors in homogenates of rat brain minus cerebellum. Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50's in the low nanomolar range. At the central mu receptor, nalmefene bound with an IC50 of 1.0 nM, equal to that of naltrexone and approximately four times lower than that of naloxone. At central kappa and delta sites the IC50's for nalmefene were somewhat lower than those of naltrexone and considerably lower than those of naloxone. All three antagonists had sodium indices less than 1.0. These results indicate that nalmefene is a universal opiate antagonist, has no agonist character at the central mu site and binds more effectively to central opiate receptors than either naloxone or naltrexone.

Animals↗

Presence of a blood-nerve barrier within blood vessels of frog sciatic nerve.

The morphological correlates of protein permeability in endoneurial blood vessels of the frog sciatic nerve were investigated. The endothelial cells of these vessels possess numerous free and anastomosing vesicles at both their lumenal and ablumenal surfaces. The cells are joined by junctions characterized by one or two areas of membrane apposition. However, vesicular transport, transcellular channels or open junctions are not found. The protein tracers horseradish peroxidase and microperoxidase remained confined in the vessels after intravascular injection. Likewise, if injected into the endoneurium, horseradish peroxidase did not enter the vascular lumen. The endothelium of frog endoneurial blood vessels forms an effective barrier to protein tracers.

Animals↗

Morphology of endoneurial blood vessels of frog sciatic nerve during vascular perfusion.

In order to determine if increased injection pressures can alter the permeability and ultrastructure of blood vessels of the frog blood-nerve barrier, these vessels were examined following perfusion of the iliac artery at rates of 0.21 or 0.82 ml/min. At either perfusion rate, endoneurial blood vessel profiles were clearly evident and the surface area of these vessels amounted to 60% of the surface area of the perineurium. In all vessels a large number of vesicles were present within the endothelial cells. Many were attached by necks to one or the other plasma membrane, but no transcellular channels were evident. At the higher flow rate no changes in vesicles or junctions were seen, but blebs and blisters were evident at the luminal membranes of the endoneurial endothelium. When microperoxidase was perfused at 0.82 ml/min, reaction product frequently flooded the endothelial cells, was found as clumps on the cell surface, and was distributed within the endoneurial space. These changes represent the only ultrastructural evidence of endothelial cell damage and altered permeability in response to increased rate of perfusion.

Animals↗

Computerized 24-hour ambulatory esophageal pH monitoring and esophagogastroduodenoscopy in the reflux patient. A comparative study.

Ambulatory 24-hour esophageal pH monitoring and esophagogastroduodenoscopy were performed in 72 patients with symptoms suggestive of gastroesophageal reflux. Additionally, 22 asymptomatic healthy volunteers underwent pH monitoring. In patients with classic reflux symptoms and endoscopic esophagitis, a mean of 5.41 minutes/hour of reflux below pH 4 was found compared to 0.70 minutes/hour in controls (p less than 0.0001). The mean number and duration of reflux events in this group were 1.51 events/hour and 4.0 minutes/event, compared with 0.31 events/hour and 2.26 minutes/event in volunteers (p less than 0.001, p less than 0.01). A new system for ambulatory esophageal pH monitoring is presented using a pH-sensitive radiotelemetry pill or a pH probe and computerized methods for ambulatory data collection, analysis, and storage. An overall sensitivity of 76% was obtained with a 91% selectivity for detection of acid reflux in 51 patients having classic symptoms of gastroesophageal reflux. Ambulatory pH monitoring was positive for acid reflux in seven of 11 patients with normal endoscopic findings. Conversely, eight of 12 patients with normal pH monitoring had endoscopic esophagitis. In 19 patients presenting with atypical symptoms or previous gastric surgery, endoscopic findings were normal in 15. Nine of these 15 were identified as acid refluxers by pH monitoring. A combined approach using both pH monitoring and endoscopy is warranted for maximal detection and quantification of disease. A clear clinical role for pH monitoring is seen in the early diagnosis of acid reflux, particularly in patients having normal endoscopic findings with nonspecific gastrointestinal complaints or previous gastric operations.

Adult↗