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At least 811 records · Page 45Linked to original sources

PubMed1990

Initial clinical results of a 430 MHz microwave hyperthermia system using a lens applicator.

The applicability of a 430 MHz microwave (MW) hyperthermia system using an electric field converging (lens) applicator was evaluated. Twenty-two tumors with a maximum tumor depth of less than 7 cm (10 chest wall tumors, 8 abdominal and pelvic tumors, 2 extremity tumors, and 2 neck tumors) were treated with the lens applicator heating system for a total of 72 sessions in conjunction with irradiation or chemotherapy. Of the 72 heat sessions, our treatment goal of 30 min of hyperthermia with all monitored tumor temperatures above 42 degrees C was achieved in 31 sessions (43%). The average tumor temperature was 42.5, 43.1, 42.0, and 42.0 degrees C for chest wall, abdominal and pelvic, extremity, and neck tumors, respectively; similarly 88, 83, 64 and 50% of monitored points exceeded 41 degrees C. A lens applicator heating system increased the penetration depth of MW, and tumor temperature of 41 degrees C at 5 cm from the surface was easily achieved with a four-aperture lens applicator. Of the 22 tumors, 10 tumors exhibited complete response (CR), 7 partial response (PR) and 5 no response (NR). These results suggest that the lens applicator heating system is useful for heating localized subsurface tumors with a maximum tumor depth of 5-6 cm.

Adenocarcinoma↗

PubMed1996

Toward selective elicitation of TH1-controlled vaccination responses: vaccine applications of bacterial surface layer proteins.

Bacterial surface layer proteins have been utilized as combined vaccine carrier/adjuvants and offer a number of advantages in these applications. The crystalline protein arrays contain functional groups in precisely defined orientations for coupling of haptens. Conventional applications of S-layer vaccines do not cause observable trauma or side effects. Depending on the nature of the S-layer preparations, antigenic conjugates will induce immune responses of a predominantly cellular or predominantly humoral nature. Immune responses to S-layer-hapten conjugates are also observed following oral/nasal application. In the present contribution, the status of investigations with S-layer conjugates in three main immunological projects is reviewed. In a project aimed at immunotherapy of cancer, conjugates of S-layer with small, tumor-associated oligosaccharides have been found to elicit hapten-specific DTH responses. An enlarged program of chemical synthesis has now been initiated to prepare a complete set of mucin-derived, tumor-associated oligosaccharides and their chemically modified analogues for elicitation of cell-mediated immune responses to certain tumors in humans. In another application, oligosaccharides derived from capsules of Streptococcus pneumoniae type 8 have been linked to S-layer proteins and have been found to elicit protective antibody responses in animals. Most recently, allergen S-layer conjugates have been prepared with the intention to suppress the TH2-directed, IgE-mediated allergic responses to Bet nu 1, the major allergen of birch pollen. In the former two applications, the S-layer vaccine technology appears to offer the versatility needed to direct vaccination responses toward predominant control by TH1 or TH2 lymphocytes to meet the different therapeutic or prophylactic requirements in each case. In the third application, work has progressed to a preliminary stage only.

Adjuvants, Immunologic↗

PubMed1984

Radiation leakage from linac electron applicator assembly.

The electron beam applicator system currently in use on the linear accelerator is constructed of light-weight fiberglass and aluminum. With an applicator in place on the accelerator, the photon collimator jaws are automatically set several centimeters greater than the electron field size projected at the patient's surface. To ensure that no regions of high dose levels exist outside the useful beam, ionization and film measurements were made to quantitate the amount of leakage radiation through the 10 cm X 10 cm and 25 cm X 25 cm applicators. In most regions, the ionization levels at the patient's surface were below 5% of the central axis dose. In one area for the 25 cm applicator, the percentage ionization was 8.5%, which could be reduced by the addition of a small piece of 1/8 inch thick lead. However, ionization levels on the outside surface of the applicator were found to be considerably higher at certain locations for the 25 cm applicator. Results for 6, 9, 12 and 20 MeV electrons are reported here.

Electrons↗

PubMed1990

The effect of applicator geometry on dose specification in cervical cancer.

The effect of variation of applicator geometry on classic parameters of dose specification was studied in 90 Fletcher-Suit radium applications in women with cervical cancer. Five statistically significant factors were identified by multiple linear regression analysis and quantified: mg of radium in the colpostats, mg of radium in the tandem, lateral displacement of the colpostats in the frontal plane, vertical separation between the colpostat and tandem sources, and anterior-posterior displacement of the colpostats relative to the tandem. These factors were used to predict "traditional" (i.e., bladder, rectum, and point A) and ICRU dose specification parameters as a function of applicator geometry. Applicator geometry had little effect on the product of ICRU volume specification components, but it greatly affected the individual ICRU components and "traditional" calculation points. Linear regression equations were generated to predict the magnitude of such changes so that the effects of variations in applicator geometry at various prescription points could be predicted radiographically, with subsequent confirmation by computerized dosimetry. Although such regression equations do not replace 3-dimensional computerized dosimetry, they aid applicator placement and treatment planning.

Brachytherapy↗

PubMed1993

Deep regional hyperthermia: comparison between the annular phased array and the sigma-60 applicator in the same patients.

PURPOSE: Several institutions have accumulated clinical experience with the annular array as well as with the Sigma applicator. There exist only limited data in comparison of both heating devices possibly favoring the annular array over the Sigma applicator with regard to tumor temperatures and acute toxicity. The objective of this study was to record temperature distributions at identical sites in tumor and normal tissue in the same patients treated with each device. METHODS AND MATERIALS: Eighteen patients with advanced pelvic tumors were treated on successive occasions with regional hyperthermia using the annular phased array applicator usually driven at 60-80 MHz or the Sigma applicator usually driven at 70-90 MHz. In all patients detailed thermal mapping and temperature analysis for tumor and normal tissues could be performed. RESULTS: Regardless the device used the acute toxicity was treatment limiting in nearly 50% of the treatments. Systemic stress was treatment limiting in 30% of the treatments with both devices although systemic parameters (core temperature, heart rate, changes in blood pressure) were higher with the annular array. The overall mean minimum, average and maximum tumor temperature observed were 39.5 +/- 1.0 degrees C, 40.9 +/- 1.4 degrees C, 42.7 +/- 2.3 degrees C for the annular array and 39.3 +/- 0.9 degrees C, 40.9 +/- 1.4 degrees C, and 42.5 +/- 1.7 degrees C for the Sigma applicator. The time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of all measured sites were 41.7 +/- 2.1 degrees C, 40.8 +/- 1.4 degrees C, 39.9 +/- 1.2 degrees C for the annular array and 41.7 +/- 1.4 degrees C, 41.0 +/- 1.3 degrees C, and 40.1 +/- 1.0 degrees C, for the S-60. The difference was not statistically significant. With regard to normal tissue temperatures a trend to higher maximum temperatures in the deep muscle and fat tissue was evident for the Sigma applicator. The overall minimum and average normal tissue temperatures in the deep muscle and fat tissue and the rectum and the time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of the measured sites differ not statistically significant. CONCLUSION: These results indicate that there continue to be unresolved limitations in achieving temperature elevation in deep seated tumors of the pelvis with radiative coherent EM wave techniques using amplitude and phase steering capabilities without any special optimization procedure.

Adult↗

PubMed1994

Generation and applications of monoclonal antibodies for livestock production.

Monoclonal antibodies (MCAs) have found widespread applications in livestock production. Although the generation of murine MCAs is at present a routine, the production of homologous MCAs, especially important for in vivo applications, is still hampered by the lack of efficient homologous fusion partners for immortalization of antibody producing lymphocytes of livestock species. At present, MCAs are used in immunodiagnostic tests e.g. to monitor livestock reproduction and quality of livestock products. In the future MCAs will also be used in immunosensors for real-time and on-site applications in the same areas. The commercial application of MCAs for the immunomodulation of (pharmacologically induced) physiological processes underlying important (re)production traits is at present limited to the use of anti-PMSG MCAs in PMSG-induced superovulation. However, many potentially interesting applications are under investigation (e.g. immunopotentiation of growth hormone to enhance growth; immunocytolysis of adipocytes to increase lean meat production; immunoneutralization of GnRH for immunocastration; immunoimitation of hormone activity with anti-idiotype antibodies). Attempts to use specific MCAs for the sexing of embryos have been disappointing, mainly because of the relatively low accuracy. In the future, MCAs against membrane proteins which are specific for X- or Y-chromosome bearing spermatozoa might be used for bulk separation of livestock sperm. In general, it is expected that engineered (homologous) recombinant MCAs will largely contribute to the development of a new generation of rapid immunodiagnostic tests and effective immunomodulation applications. They will further increase the use of MCAs in livestock production.

Journal Article↗

PubMed1995

Ontology-based configuration of problem-solving methods and generation of knowledge-acquisition tools: application of PROTEGE-II to protocol-based decision support.

PROTEGE-II is a suite of tools and a methodology for building knowledge-based systems and domain-specific knowledge-acquisition tools. In this paper, we show how PROTEGE-II can be applied to the task of providing protocol-based decision support in the domain of treating HIV-infected patients. To apply PROTEGE-II, (1) we construct a decomposable problem-solving method called episodic skeletal-plan refinement, (2) we build an application ontology that consists of the terms and relations in the domain, and of method-specific distinctions not already captured in the domain terms, and (3) we specify mapping relations that link terms from the application ontology to the domain-independent terms used in the problem-solving method. From the application ontology, we automatically generate a domain-specific knowledge-acquisition tool that is custom-tailored for the application. The knowledge-acquisition tool is used for the creation and maintenance of domain knowledge used by the problem-solving method. The general goal of the PROTEGE-II approach is to produce systems and components that are reusable and easily maintained. This is the rationale for constructing ontologies and problem-solving methods that can be composed from a set of smaller-grained methods and mechanisms. This is also why we tightly couple the knowledge-acquisition tools to the application ontology that specifies the domain terms used in the problem-solving systems. Although our evaluation is still preliminary, for the application task of providing protocol-based decision support, we show that these goals of reusability and easy maintenance can be achieved. We discuss design decisions and the tradeoffs that have to be made in the development of the system.

Artificial Intelligence↗

PubMed2005

Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.

Superparamagnetic iron oxide nanoparticles (SPION) with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, hyperthermia, drug delivery and in cell separation, etc. All these biomedical and bioengineering applications require that these nanoparticles have high magnetization values and size smaller than 100 nm with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. In addition, these applications need special surface coating of the magnetic particles, which has to be not only non-toxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. To this end, most work in this field has been done in improving the biocompatibility of the materials, but only a few scientific investigations and developments have been carried out in improving the quality of magnetic particles, their size distribution, their shape and surface in addition to characterizing them to get a protocol for the quality control of these particles. Nature of surface coatings and their subsequent geometric arrangement on the nanoparticles determine not only the overall size of the colloid but also play a significant role in biokinetics and biodistribution of nanoparticles in the body. The types of specific coating, or derivatization, for these nanoparticles depend on the end application and should be chosen by keeping a particular application in mind, whether it be aimed at inflammation response or anti-cancer agents. Magnetic nanoparticles can bind to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumour using an external magnetic field or can be heated in alternating magnetic fields for use in hyperthermia. This review discusses the synthetic chemistry, fluid stabilization and surface modification of superparamagnetic iron oxide nanoparticles, as well as their use for above biomedical applications.

Animals↗

PubMed2005

Microfabrication of poly (glycerol-sebacate) for contact guidance applications.

Controlling cell orientation and morphology through topographical patterning is a phenomenon that is applicable to a wide variety of medical applications such as implants and tissue engineering scaffolds. Previous work in this field, termed contact guidance, has demonstrated the application of this cellular response on a wide variety of material substrates such as silicon, quartz, glass, and poly(di-methyl siloxane) typically using ridge-groove geometries with sharp feature edges. One limitation of these studies in terms of biomedical applications is the choice of material. Therefore, demonstrating contact guidance and topography in a biodegradable material platform is a promising strategy for controlling cellular arrangements in tissue engineering scaffolds. This study investigates several strategies to advance contact guidance strategies and technology to more practical applications. Flexible biodegradable substrates with rounded features were fabricated by replica-molding poly(glycerol-sebacate) on sucrose-coated microfabricated silicon. Bovine aortic endothelial cells were cultured on substrates with microstructures between 2 and 5 microm in wavelength and with constant feature depth of 0.45 microm. Cells cultured on substrates with smaller pitches exhibited a substantially higher frequency of cell alignment and smaller circularity index. This work documents the first known use of using a flexible, biodegradable substrate with rounded features for use in contact guidance applications. The replica-molding technique described here is a general process that can be used to fabricate topographically patterned substrates with rounded features for many biomaterials. Furthermore, these results may lead to further elucidation of the mechanism of cell alignment and contact guidance on microfabricated substrates.

Animals↗

PubMed2005

CT computer-optimized high-dose-rate brachytherapy with surface applicator technique for scar boost radiation after breast reconstruction surgery.

PURPOSE: Immediate breast reconstruction has become increasingly prevalent after mastectomy for breast cancer. Postoperative scar boost radiation for the reconstructed breast presents many planning challenges due to the shape, size, and curvature of the scar. High-dose-rate (HDR) surface applicator brachytherapy is a novel and effective method of delivering scar boost radiation. Two cases, one with a saline implant and one with a transverse rectus abdominis musculocutaneous flap reconstruction, illustrate the method and advantages of HDR optimization of surface applicators. METHODS AND MATERIALS: For 2 patients a mold of the breast was made with Aquaplast sheets. A reproducible system was used for arm positioning. Skin fiducials, including tattoos from external beam planning, were matched to fiducials on the mold. HDR catheters were sited on the mold at 1cm intervals, with the central catheter situated along the scar. Topographically, both scars demonstrated extreme curvature in both craniocaudal and mediolateral directions. A CT computer-optimized HDR plan was developed, with the reference dose prescribed at the skin surface. The dosimetry was compared to single-field and matched-field electron plans. RESULTS: This surface applicator technique provided a uniform skin dose of 100% to the entire clinical target volume (CTV) without hot spots in both patients. The patient position and surface applicator setup were consistently reproducible. The patients tolerated the treatment well with minimal skin erythema. In the single-field electron plan, skin dose was decreased to 50% at the periphery of the scar. Matching fields addressed this depth dose decrement, but resulted in large localized hot spots of more than 200% centrally in each field. CONCLUSION: CT computer-optimized HDR surface applicator brachytherapy provided a reproducible homogeneous method of treating highly curved scars on the reconstructed breast. Electron beam treatment would result in longer and more complex treatments yet still provide a less homogeneous dose than this surface applicator technique.

Brachytherapy↗

PubMed2006

Rise of testosterone, nortestosterone, and 17beta-estradiol concentrations in peripheral blood plasma of pigs after sublingual application in vivo.

Application of endogenous anabolic steroids to meat producing animals is not allowed in the EU. In other countries application is practised due to a low oral activity based on an efficient first liver passage. This contrasts with pharmacological investigations where steroids were readily absorbed by the buccal and sublingual mucosa using absorption enhancers. An in vivo study was performed to clarify possible absorption after sublingual applications of one milligram portions of either testosterone (T), 17beta-estradiol (E), or nortestosterone (NT) in sesame oil to castrated male pigs (n=5) without specific delivery systems during anaesthesia. Blood samples were drawn using jugular vein catheters for 15 min before and 3h after application. Hormone concentrations were determined by Radioimmunoassay for T and E or Enzymeimmunoassay for NT. For all steroids a slight increase was measurable one minute after application. Maximal values for T, E, and NT were 2.5 ng/ml, 1.5 ng/ml and 4.2 ng/ml, respectively, and were observed after 10 min. The concentrations of the three steroids decreased slowly thereafter but were still significantly elevated 1-3h after application. Oral absorption of steroids without enhancers should be considered in risk analysis.

Absorption↗

PubMed2006

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

Action Potentials↗

PubMed2006

Kinetics of 3-(4-methylbenzylidene)camphor in rats and humans after dermal application.

The toxicokinetics of 4-MBC after dermal administration were investigated in human subjects and in rats. Humans (3 male and 3 female subjects) were exposed to 4-MBC by topical application of a commercial sunscreen formulation containing 4% 4-MBC (w/w), covering 90% of the body surface and resulting in a mean dermal 4-MBC dose of 22 mg/kg bw. In rats, dermal 4-MBC doses of 400 and 2000 mg/kg bw were applied in a formulation using an occlusive patch for 24 h. Concentrations of 4-MBC and its metabolites were monitored over 96 h in plasma (rats and humans) and urine (humans). In human subjects, plasma levels of 4-MBC peaked at 200 pmol/ml in males and 100 pmol/ml in females 6 h after application and then decreased to reach the limit of detection after 24 h (females), respectively, 36 h (males). After dermal application of 4-MBC, peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 50-80 pmol/ml at 12 h and of 3-(4-carboxybenzylidene)camphor were 100-200 pmol/ml at 24 h. In male and female rats, peak plasma levels of 4-MBC were 200 (dose of 400 mg/kg bw) and 1 200 pmol/ml (dose of 2000 mg/kg bw). These levels remained constant for up to 24-48 h after dermal application. Peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 18,000 pmol/ml (males) and of 3-(4-carboxybenzylidene)camphor were 55,000 pmol/ml (females) between 48 and 72 h after application of the high dose of 4-MBC. In human subjects, only a small percentage of the dermally applied dose of 4-MBC was recovered in the form of metabolites in urine, partly as glucuronides. The obtained results suggest a more intensive biotransformation of 4-MBC in rats as compared to humans after dermal application and a poor absorption of 4-MBC through human skin.

Administration, Cutaneous↗

PubMed2005

Heavy metal removal from contaminated sludge for land application: a review.

In recent years, various methods for heavy metal removal from sewage sludge have been extensively studied in order to minimize the prospective health risks of sludge during land application. In this paper, a comparative review and critical analysis of the application of chemical extraction, bioleaching, electroreclamation, and supercritical fluid extraction (SFE), in removing heavy metals from contaminated sludges is presented. Moreover, speciation studies, which can indicate ease of leachability of the different forms of heavy metals in sludge, are also presented. Experimental studies revealed a broad range in metal extraction efficiencies of the different extraction technologies. Acid treatment seemed to effectively remove Cd, attaining as much as 100% removal for some studies, as compared to bioleaching. SFE also gave higher removal efficiency than bioleaching. Cr, Pb and Ni seemed to be also effectively removed by the acid treatment. For the removal of Cu, Mn and Zn, the bioleaching process seemed to be appropriate with maximum removal efficiencies of 91%, 93% and 96% for the three metals, respectively, and as high as 64% minimum removal efficiency for Zn. The SFE process also gave good results for Cu, Mn and Zn removal. Electroreclamation exhibited better removal efficiency for Mn, but is still inferior to acid treatment and bioleaching processes. For chemical extraction, because of the adverse impacts that can result from the use of inorganic acids and complexing agents, interest can be directed more toward utilizing organic acids as extracting agents because of their biodegradability and capability to remove metals at mildly acidic condition, hence requiring less acid. The bioleaching process, although it seems to give a higher yield of metal extraction with lower chemical cost than chemical extraction, may be limited by the inability of the system to cope with the natural environmental conditions, requires strict monitoring of aeration rate and temperature and has applicability to only low sludge solids concentration. A full-scale study would be useful to better assess the efficiency of the process. The electroreclamation technology is limited by its relatively higher energy consumption and limited applicability to sludge. The SFE method, on the other hand, is limited by the complexity of the process and the cost of ligands suitable for effective metal extraction. Both of these technologies are still in their early stage of application and hence there is a need for further basic and applied studies. Finally, the common advantage for almost all treatment technologies studied is that the extraction efficiencies for some metals are high enough to remove metals from sludge to levels suitable for land application.

Industrial Waste↗

PubMed1999

Development of inflammation after application of mustard oil or glutamate to the rat temporomandibular joint.

Application of the small-fibre excitant and inflammatory irritant mustard oil or the excitatory amino-acid receptor agonist glutamate to the rat temporomandibular joint (TMJ) region evokes similar changes in jaw-muscle activity, suggesting that peripheral application of glutamate may be nociceptive. Application of mustard oil to the TMJ region is also inflammatory, but, it is not clear if application of glutamate is equally inflammatory. In this study the extent of plasma-protein extravasation and oedema induced by mustard oil application to the TMJ region was compared with that induced by glutamate. Application of mustard oil resulted in plasma-protein extravasation into the TMJ tissues and oedema of the TMJ region. In contrast, glutamate did not cause plasma-protein extravasation or oedema.

Analysis of Variance↗

PubMed1998

Depressive effects of segmental and heterotopic application of transcutaneous electrical nerve stimulation and piezo-electric current on lower limb nociceptive flexion reflex in human subjects.

OBJECTIVES: To evaluate quantitatively the effectiveness and clinical relevance of various parameters of electrical stimulation used to relieve acute and chronic pain and to further knowledge of the mechanisms that may underlie the physiologic response produced by the transcutaneous application of each type of current. DESIGN: A nociceptive flexion reflex (RIII reflex) elicited in the lower limb by electrical stimulation of the sural nerve at the ankle was studied before, during, and after application of the following conditioning stimuli: (1) non-noxious transcutaneous electrical nerve stimulation (TENS)--low-intensity (2mA), short-duration (0.1 msec), and high-frequency (100Hz) rectangular pulses (TENS1); (2) noxious TENS--high-intensity (20mA), long-duration (2 msec), and low-frequency (3Hz) rectangular pulses (TENS2); (3) noxious piezo-electric current (PEC)--high-voltage, low-charge, low-intensity, and low-frequency rectangular pulses delivered by a piezo-electric ceramic device (PECs1); (4) a sham PEC situation in which the piezo-electric device did not produce any electric current (Sham PEC). Each conditioning stimulus (TENS1, TENS2, PECs1, Sham PEC) was applied for a 2-minute period either segmentally on the sural nerve itself or heterotopically on the skin overlying the first interosseous space of the contralateral hand. PARTICIPANTS: Twenty-four healthy volunteers (14 women, 10 men, 19 to 52 years of age), who were briefed and familiarized with the experimental procedure. During the experimental sessions, subjects were prone in bed to ensure muscular relaxation. MEASURES: Value of the nociceptive RIII reflex before, during, and after application of conditioning stimuli in the four procedures described above. This reflex was selected because it has been shown to be an objective and physiologic correlate of pain. RESULTS: Non-noxious TENS1 stimulation applied segmentally produced inhibitions of the RIII reflex only during the 2-minute conditioning period. When given segmentally, the noxious TENS2 stimulation produced a facilitatory effect during the 2 minutes of application, followed by significant inhibitory after-effects. The administration of TENS2 heterotopically resulted in inhibitions of the RIII reflex both during and after the 2-minute conditioning period. Application of PECs1, whether segmentally or heterotopically, produced powerful and long-lasting inhibitory after-effects, especially with the heterotopic paradigm. These effects were associated with long-lasting local changes to the skin of the neurogenic inflammation type, which were well tolerated by all subjects. Application of Sham PEC did not result in significant modification of either the RIII reflex or the skin. CONCLUSIONS: These data are discussed in terms of possible spinal and supraspinal mechanisms involving inhibitory descending controls and underline the potential clinical use of PECs1 in the treatment of pain.

Adult↗

PubMedDate not supplied

Different responses to repeated applications of zingerone in behavioral studies, recordings from intact and cultured TG neurons, and from VR1 receptors.

When applied repetitively to the cornea, capsaicin, the pungent compound in hot pepper, causes an initial eye-wiping response that diminishes upon repeated exposure (tachyphylaxis). This diminution, however, is not observed upon repetitive application of its pungent analogue, zingerone, to the cornea or tongue. In addition, compared with capsaicin, the lingual application of zingerone produces a gustatory response with a shorter latency and duration. Because both the tongue and the cornea are innervated by the trigeminal nerve, and because zingerone and capsaicin are structurally related, it is not evident why the responses to these compounds should give such different behavioral and psychophysical endpoints. We have addressed this issue by measuring the neural responses from rat trigeminal ganglion neurons (TG) to repeated applications of zingerone applied to the cornea, from cultured rat TG neurons, and from cloned capsaicin receptors (VR1) expressed in Xenopus oocytes and then comparing these effects to those evoked by capsaicin. Extracellular recordings from the trigeminal ganglion revealed that the responses to repeated corneal applications of 30 mM zingerone show desensitization. Cultured TG neurons, and oocytes expressing VR1 receptors, were also desensitized by repeated applications of zingerone. Electrophysiological recordings revealed that these two vanilloids could activate the same receptor (VR1), currents in the same neuron, and crossdesensitize. The more rapid onset and shorter duration responses seen with zingerone (compared with capsaicin) provides a rationalization for its more rapid onset and shorter duration gustatory response. We attribute the different behavioral responses to periodic applications of these two agonists to two competing effects: one leading to sensitization, and the other to tachyphylaxis. Which of these dominates depends on the concentration, exposure time, and interstimulus interval. Consequently, whether or not zingerone will exhibit tachyphylaxis depends critically on the experimental conditions.

Animals↗

PubMed2002

Intraoperative episcleral versus postoperative topical application of mitomycin-C for trabeculectomies.

OBJECTIVE: To assess the efficacy of a new application technique of mitomycin-C to enhance the outcome of filtering surgery in cases of complicated glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Fifty consecutive patients scheduled for glaucoma surgery in one large surgical center. INTERVENTION: Patients underwent routine trabeculectomy. In group 1, mitomycin-C (0.05 mg/ml) was applied topically to the filtering bleb on days 1, 2, and 3 after surgery (postoperative application). In group 2, mitomycin-C (0.2 mg/ml) was applied by means of to a sponge during surgery (intraoperative application). MAIN OUTCOME MEASURES: Preoperative and postoperative intraocular pressure (IOP) values, visual acuity, the need for antiglaucoma medication, previous surgical procedures, and the need for further surgical interventions were monitored. RESULTS: Sufficient follow-up data were available from 24 of 25 patients in each of the two groups. The follow-up ranged from 12 to 28 months and was evaluated at 12 months for all patients. The mean IOP decreased from 27.3 to 15.5 mmHg in group 1 and from 29.0 to 17.5 mmHg in group 2. The average number of medications decreased from 2.3 and 2.4 to 0.9 and 0.8 (P = 0.68; t test) in groups 1 and 2, respectively, at the 12-month visit. Hypotony was more frequent in group 2, in which the only case of hypotony maculopathy occurred. There was a tendency of more eyes with lower IOP values in this group. The rate of loss of visual acuity of more than 2 lines was higher in group 2. Failures were more frequent in group 2 (7 of 24) compared with group 1 (1 of 24) (P = 0.04, chi-square test). CONCLUSIONS: To our knowledge, this is the first prospective, randomized clinical study to evaluate the efficacy of this different technique of mitomycin-C application. The postoperative application of mitomycin-C was effective, having few failures. This application of mitomycin-C may be associated with a lower rate of complications when used in eyes with complicated forms of glaucoma.

Administration, Topical↗