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Holmium YAG laser sclerostomy ab externo for refractory glaucoma.

Ab externo thermal sclerostomy was performed with the holmium YAG (thulium, holmium, chromium-doped YAG crystal) laser in 21 eyes of 20 patients with refractory glaucoma. We used either the 5-fluorouracil (5-FU) or mitomycin C (MMC) antimetabolites in all cases. The rate of intraocular pressure (IOP) control defined as IOP < 21 mmHg regardless of whether antiglaucoma medication was applied postoperatively) was estimated by the life-table methods of Kaplan-Meier. The postoperative IOP control rate was 47.1% in the MMC-treated group at 57 months, and 14.3% in the 5-FU-treated group at 52 months. There were statistically significant differences in success rates between the MMC- and 5-FU-treated groups. We observed no clinically significant complications except excess filtration associated with a shallow anterior chamber in one case. This procedure is thought to have several advantages over more conventional filtration surgery; the operation time is shorter, and there is no need for intraocular manipulation, which means conjunctival trauma is minimal. However, the IOP control rate was substantially lower than that achieved via conventional trabeculectomy. Our results suggest that the selection of patients and the use of MMC is an important factor in maintaining successful filtration.

Adolescent↗

Comparison of methods for transcatheter fragmentation of gallstones.

Alternative methods have been considered for treating cholelithiasis. Compared to extracorporeal shockwave lithotripsy (ESWL), a percutaneous endoscopic approach would be more invasive, but would offer the advantage of immediate stone removal without the need for subsequent drug therapy. We performed an in vitro comparison of three methods of transcatheter cholecystolithotripsy with regard to effectiveness of stone fragmentation, damage to the gallbladder mucosa, and compatibility with percutaneous delivery systems. The three devices used for cholecystolithotripsy were the ultrasonic lithotriptor (UL), the electrohydraulic lithotriptor (EHL), and the thulium-holmium-chromium: YAG laser (THC:YAG). The UL effectively fragmented all types of stones studied, although it is necessary to hold the stone against the tip of the probe. The EHL quickly fragmented noncalcified and pigment stones simply by placing the tip in the vicinity of the stone, but calcified stones had to be held in position near the electrode. The THC:YAG was effective at fragmenting each type of stone, but the number of pulses required was quite large, corresponding to 7 min for some stones. The EHL had the most capacity for mucosal damage, followed by the THC:YAG laser. The UL produced no mucosal damage at the exposure times tested. The UL is not compatible with flexible endoscopes while the EHL and the THC:YAG are. Because of the specific advantages and disadvantages of each device, a combination of devices may be required for successful clinical cholecystolithotripsy.

Catheterization↗

Effects of lanthanum in cellular systems. A review.

Lanthanum belongs to the group of elements known as "lanthanons," which also includes cerium, europium, promethium, and thulium. It is the most electropositive element of the rare earth group, is uniformly trivalent, and is similar in its chemical properties to the alkaline earth elements. The effects of this element and its compounds on cellular systems are of considerable interest because of their increasing use in industry and as a substitute or antagonist for calcium in a variety of cellular reactions. Lanthanum is also being employed extensively in studying anatomical barriers, membrane structure, and subcellular transport systems, particularly the calcium pathway.

Animals↗

Fasting limits the increase in intracellular calcium during ischemia in isolated rat hearts.

INTRODUCTION: Fasting has been shown to limit ischemic injury and improve functional activity after global ischemia. Because calcium overload is considered a mechanism of ischemic injury, we hypothesized that fasting would limit the accumulation of intracellular calcium [Ca]i during ischemia, potentially due to reduced accumulation of intracellular sodium [Na]i. METHODS: To address this hypothesis, hearts isolated from rats fed either a normal diet or fasted for 24 hours underwent 20 min of global ischemia at 37 degrees. In addition to functional parameters, [Na]i and [Ca]i were measured using 21Na and 19F spectroscopy using thulium-DOTP-5 and 5F-BAPTA, respectively. In vitro measurement of sarcoplasmic reticulum calcium uptake and release, as well as activity of the sarcolemmal Na-Ca exchanger, was performed in hearts from fed and fasted animals under baseline and ischemic conditions. RESULTS: Hearts from fasted animals showed greater recovery of developed pressure (37+/-9 vs. 11+/-6 cm H2O, p < 0.05) and less contracture (end-diastolic pressure 25+/-2 vs. 47+/-2 cm H2O, p < 0.05) by the end of the reperfusion period. [Na]i was similar in the 2 groups during the first half of the ischemic period, albeit with a higher concentration of [Na]i in hearts from fed compared to fasted animals at reperfusion. Fasting markedly limited calcium accumulation during ischemia, with end-ischemic calcium being 419+/-46 nM in the hearts from fasted animals and 858+/-140 nM in the hearts from fed animals (p < 0.01). There was no significant effect of fasting on calcium uptake or release by the SR, nor on sarcolemmal Na-Ca exchange activity. CONCLUSIONS: Fasting for 24 hours improves functional recovery and markedly limits [Ca]i accumulation during ischemia and early reperfusion. The mechanism for this phenomenon remains to be elucidated.

Animals↗

Crystallographic determination of lanthanide ion binding to troponin C.

X-ray intensity data to 2.8 A resolution were collected from each of three crystals of turkey skeletal troponin C (TnC) that had been soaked individually in solutions containing the lanthanide ions europium, thulium and lutetium. Each of the resulting difference electron density maps computed for the three data sets showed three lanthanide ion-binding sites on the TnC molecule. Two of the sites are approximately coincident with the Ca2+ positions in binding loops III and IV and the third site is near the Ca2+-free loop I. The mode of ion binding in loop I is different from that commonly observed for Ca2+ in the Ca2+-binding proteins.

Animals↗

Spontaneous Fanconi syndrome in the dog.

Three dogs with spontaneous renal tubular defects similar to idiopathic Fanconi syndrome are characterized. Renal clearance studies revealed a fractional reabsorption of glucose ranging from 31% to 82%. Abnormal glucose thulium values were present in all dogs. A generalized aminoaciduria occurred in two dogs while one had aminoaciduria characteristic of canine cystinuria. Fractional reabsorption of phosphate ranged from 47% to 79%. In vitro uptake of alpha-methyl-D-glucoside was significantly depressed (p less than 0.001). In vitro uptake of amino isobutyric acid was similar to controls. Renal biopsy revealed nonspecific interstitial change in two dogs and normal histology in the other. These animals represent a useful new model for the study of renal tubular transport defects.

Amino Acids↗

Determination of liposomal encapsulation efficiency using proton NMR spectroscopy.

A rapid and simple approach using 1H NMR was developed for determination of liposomal encapsulation efficiency without the need for physical separation of entrapped and non-entrapped marker. Measurements were made using a marker (homocarnosine) with a pH-sensitive 1H chemical shift in the presence of a pH gradient across the phospholipid vesicle membrane, or by addition of the chemical shift reagent, thulium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-(methylene phosphonic acid sodium salt) (TmDOTP5-). The measured encapsulation efficiencies for the liposomal dispersions prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) through extrusion using 50, 200 and 1000 nm polycarbonate membranes were found to be identical using the two different experimental approaches.

Carnosine↗

Lasers and other thermal stimulators for activation of skin nociceptors in humans.

Pain can be induced by thermal, chemical, and mechanical stimulation in animals and man. Of the thermal stimulation modalities, heat is the most commonly used, as a variety of reliable stimulation techniques are available. Heat is a natural stimulus modality to evoke pain, and it has been used to study animal nociception and human pain perception for (a) examining the mechanisms of tissue injury and sensitisation and (b) quantifying the therapeutic effects of pharmacological, physical, and psychological interventions. This paper summarises the current understanding of the physiology and psychophysical response to painful heat stimulation in humans. By understanding the underlying mechanisms, new methods of heat stimulation may be developed for basic and clinical applications. Traditionally, contact heat, indirect thermal heat by focused light bulb, and laser pulses have been the methods used to induce heat pain in humans for experimental and clinical studies. The following lasers have been used in pain research: argon (488-515 nm), copper vapour (510-577 nm), semiconductor (e.g. 970 nm), neodymium-YAG (1064 nm), thulium-YAG (2000 nm), and CO(2) (10,600 nm).

Hot Temperature↗

Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study.

The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. To investigate the somatotopic organization of the nociceptive system, we applied Thulium-YAG-laser evoked pain stimuli, which have no concomitant tactile component, to the dorsum of the left hand and foot in randomized order. We used single-trial functional magnetic resonance imaging (fMRI) to assess differential hemodynamic responses to hand and foot stimulation for the group and in a single subject approach. The primary somatosensory cortex (SI) shows a clear somatotopic organization ipsi- and contralaterally to painful stimulation. Furthermore, a differential representation of hand and foot stimulation appeared within the contralateral opercular--insular region of the secondary somatosensory cortex (SII). This result provides evidence that both SI and SII encode spatial information of nociceptive stimuli without additional information from the tactile system and highlights the concept of a redundant representation of basic discriminative stimulus features in human somatosensory cortices, which seems adequate in view of the evolutionary importance of pain perception.

Adult↗

Common cortical network for first and second pain.

We measured, with whole-scalp magnetoencephalography, evoked fields from 10 healthy subjects to 1-ms thulium-laser stimuli that selectively activated nociceptive nerve fibers. The stimuli were delivered to the dorsum of the subject's left hand. The earliest cortical responses peaked at 165 +/- 7 ms, agreeing with the conduction velocity of Adelta-fibers. To stimulate unmyelinated C-fibers, we modified the method of Bragard et al. [Bragard, D., Chen, A.C., Plaghki, L., 1996. Direct isolation of ultra-late (C-fibre) evoked brain potentials by CO2 laser stimulation of tiny cutaneous surface areas in man. Neurosci. Lett. 209, 81-84], by decreasing the total energy of the laser beam and by restricting the size of the stimulated skin area to 0.2-0.3 mm2. The earliest cortical responses to these stimuli peaked at 811 +/- 14 ms. Bilateral activation of the SII cortices was detected in all 10 subjects to Adelta and in 8 subjects to C stimuli, emphasizing the importance of the SII cortex in processing of pain. Additional activation was observed in the posterior parietal cortex (PPC), probably related to sensorimotor coordination targeted to produce precise motor acts that reduce or prevent the pain; the PPC activation may have been accentuated by the required continuous evaluation of the perceived pain. In contrast to some earlier studies, we did not observe activation of the primary somatosensory cortex (SI). Additional activations to both types of stimuli were detected in the cingulate cortex (three subjects) and in the bilateral insular cortex (two subjects). These results implicate that the nociceptive inputs mediated by the Adelta- and C-fibers are processed in a common cortical network in different time windows. Reliable temporospatial characterization of cortical responses to first and second pain offers a unique tool for basic and clinical neuroscience to study the two distinctive pain fiber systems at cortical level.

Adult↗

Neuromagnetic SII responses do not fully reflect pain scale.

To elucidate the role of somatosensory cortices in coding pain magnitude, we recorded the neuromagnetic responses of ten subjects to mild, moderate, and severe pain stimulation by delivering thulium-laser pulses on the dorsum of the left hand. The stimulus intensities for producing different pain levels were determined individually, and the mean values across subjects were 255, 365, and 490 mJ for mild, moderate, and severe pain, respectively. We obtained 40 responses for each intensity condition, and analyzed the averaged cortical signals by multi-dipole modeling. All subjects showed consistent activation over the bilateral secondary somatosensory (SII) cortices for each intensity level, peaking around 150-230 ms, with 15-ms earlier on the contralateral hemisphere. The SII dipole strength was significantly larger for the moderate than for the mild pain stimulation, but lacked further increase as the pain magnitude elevated to the severe level. In contrast, the primary somatosensory cortical response was detected in only half of our subjects, and thus it seemed difficult to evaluate its role in pain intensity coding. Our results suggest that activation strength in human SII cortices reflects the magnitude of peripheral noxious inputs only up to the moderate level, and some other cerebral correlates may get involved in sensing a further increment of pain magnitude.

Adult↗

Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings.

Approximately 70-80% of women meeting criteria for borderline personality disorder (BPD) report attenuated pain perception or analgesia during non-suicidal, intentional self-mutilation. The aim of this study was to use laser-evoked potentials (LEPs) and psychophysical methods to differentiate the factors that may underlie this analgesic state. Ten unmedicated female patients with BPD (according to DSM-IV) and 14 healthy female control subjects were investigated using brief radiant heat pulses generated by a thulium laser and five-channel LEP recording. Heat pulses were applied as part of a spatial discrimination task (two levels of difficulty) and during a mental arithmetic task. BPD patients had significantly higher heat pain thresholds (23%) and lower pain ratings (67%) than control subjects. Nevertheless, LEP amplitudes were either normal (N1, P2, P3) or moderately enhanced in BPD patients (N2). LEP latencies and task performance did not differ between patients and control subjects. The P3 amplitudes, the vertex potential (N2-P2), and the N1, which is generated near the secondary somatosensory cortex, were significantly reduced during distraction by mental arithmetic in both groups. In addition, P3 amplitudes reflected task difficulty. This study confirms previous findings of attenuated pain perception in BPD. Normal nociceptive discrimination task performance, normal LEPs, and normal P3 potentials indicate that this attenuation is neither related to a general impairment of the sensory-discriminative component of pain, nor to hyperactive descending inhibition, nor to attention deficits. These findings suggest that hypoalgesia in BPD may primarily be due to altered intracortical processing similar to certain meditative states.

Adult↗

Localization of touch versus heat pain in the human hand: a dissociative effect of temporal parameters on discriminative capacity and decision strategy.

We studied the influence of temporal parameters on localization of monofilament-evoked touch versus thulium laser-induced and C fiber-mediated pain in human subjects. Stimuli were applied at interstimulus intervals (ISIs) varying from 1 to 9 s to determine discrimination between successive stimulus sites in the palmar skin. Localization threshold was about two times higher for heat pain than touch. The localization threshold for pain, but not touch, decreased with prolongation of the ISI from 1 to 7-9 s, and it remained higher for pain even at the ISI of 9 s. The response time was longer for pain than touch, and it increased with an increase in the ISI, independent of the modality. Discriminative capacity, as assessed by the receiver operating characteristics curve, was markedly better for touch than pain. The discriminative capacity decreased with an increase of the ISI, but only for touch. The results indicate that localization is more accurate for touch than pain. Temporal summation of C fiber-evoked pain contributes to the reduced accuracy of pain localization if the ISI is < or = 3 s. Additionally, temporal factors dissociatively influence the response strategy in the tactile versus pain localization task with the prolongation of the ISI from 1 to 9 s. Due to this strategy change, localization threshold for touch remains constant at prolonged ISIs, in spite of a decrease in discriminative capacity. In a cutaneous localization task, the subject's accuracy and response strategy vary with the modality and temporal parameters of sequential test stimulation.

Adult↗

Ionic charge, radius, and potential control root/soil concentration ratios of fifty cationic elements in the organic horizon of a beech (Fagus sylvatica) forest podzol.

The root/organic soil concentration ratio; R/S) of 50 cationic mineral elements was related to their ionic properties, including ionic radius (r), ionic charge (z), and ionic potential (z/r or z2/r). The materials studied were ectomycorrhizal beech (Fagus sylvatica L.) roots and their almost purely organic soil substrate, the O-horizon (mor; raw humus) of a Podzol in South Sweden, developed in a site which has been untouched by forestry or other mechanical disturbance since at least 50 years and located in an area with no local sources of pollution. Elements determined by ICP-AES were aluminium, barium, calcium, iron, potassium, magnesium, manganese, sodium and strontium. Determined by ICP-MS were silver, beryllium, bismuth, cadmium, cerium, cobalt, chromium, caesium, copper, dysprosium, erbium, europium, gallium, gadolinium, hafnium, mercury, holmium, indium, lanthanum, lithium, lutetium, niobium, neodymium, nickel, lead, praseodymium, rubidium, scandium, samarium, tin, terbium, thorium, titanium, thallium, thulium, uranium, vanadium, yttrium, ytterbium, zinc and zirconium. The R/S ratios were most clearly related to the ionic potential of the cationic elements studied, which accounted for approximately 60% of the variability in R/S among elements. The ionic charge of an element was more important than the ionic radius. Elements with high ionic charge had low R/S ratios and vice versa. No clear differences in R/S between essential and non-essential plant nutrients were observed, especially when ions of similar charge were compared.

Cations↗

Magnetically aligned phospholipid bilayers with positive ordering: a new model membrane system.

A stable smectic phospholipid bilayer phase aligned with the director parallel to the magnetic field can be generated by the addition of certain trivalent paramagnetic lanthanide ions to a bicellar solution of dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in water. Suitable lanthanide ions are those with positive anisotropy of their magnetic susceptibility, namely Eu3+, Er3+, Tm3+, and Yb3+. For samples doped with Tm3+, this phase extends over a wide range of Tm3+ concentrations (6-40 mM) and temperatures (35-90 degrees C) and appears to undergo a transition from a fluid nematic discotic to a fluid, but highly ordered, smectic phase at a temperature that depends on the thulium concentration. As a membrane mimetic, these new, positively ordered phospholipid phases have high potential for structural studies using a variety of techniques such as magnetic resonance (EMR and NMR), small-angle x-ray and neutron diffraction, as well as optical and infrared spectroscopy.

Dimyristoylphosphatidylcholine↗

Subconjunctival THC:YAG laser thermal sclerostomy.

A THC:YAG laser (thulium, holmium, chromium-doped YAG crystal) was used to create thermal sclerostomies in 21 glaucomatous eyes of 19 patients. The laser is a long-pulsed (300 microsec), compact, self-contained, solid state laser operating in the near infrared (2.1 mu). A 1-mm conjunctival stab incision was made 12 mm away from the sclerostomy site to allow entry of a specially designed 22-gauge (712 mu) optic probe that delivers energy at a right angle to the long axis of the fiber. Probe insertion produced minimal disturbance of the conjunctiva. Pulse energies of 80 mJ to 120 mJ were used with a repetition rate of 5 pulses/second. Total energy levels to produce full-thickness sclerostomies ranged from 1.4 to 4.8 J. Subconjunctival 5-fluorouracil injections were administered in 15 eyes. At 3 months the mean intraocular pressure of successful cases (16) was 14 mmHg (range, 9 to 22 mmHg). Of successful cases, the mean intraocular pressure at 6 months was 13 mmHg (range, 2 to 22 mmHg). Five cases failed within the initial 3 months, and 3 additional cases failed by 6 months. The authors conclude that this full-thickness sclerostomy technique may simplify filtering surgery without anterior chamber instrumentation and with minimal conjunctival trauma.

Adult↗

2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?

To test the hypothesis that decreased hepatocyte ATP is transduced into a hepatic neuronal signal via a change in sodium pump activity, we examined the effect of 2,5-anhydro-D-mannitol (2,5-AM), which stimulates feeding behavior in rats, on intracellular sodium levels using 23Na nuclear magnetic resonance (NMR) spectroscopy. Isolated hepatocytes suspended in agarose beads were superfused with either 2.5 mM 2,5-AM or fructose in the presence of the paramagnetic shift reagent, thulium(III)(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonate)). Superfusion with 2,5-AM decreased hepatocyte ATP and increased intracellular sodium levels compared with superfusion with either fructose or shift reagent alone starting within 15 min of exposure, reaching a maximum level of 120% of baseline by 30 min and declining gradually thereafter over the next 90 min. Superfusion with fructose, which also decreased hepatocyte ATP but by less than half the amount seen with 2,5-AM, had no significant effect on cellular sodium levels. The results support the hypothesis that changes in sodium pump activity could participate in transducing a hunger stimulus associated with hepatocyte energy status into a signal for hunger.

Adenosine Triphosphate↗

Historical and current atmospheric deposition to the epilithic lichen Xanthoparmelia in Maricopa County, Arizona.

Spatial patterns of atmospheric deposition of trace elements to an epilithic lichen were assessed using a spatial grid of 28 field sites in 1998 throughout Maricopa County, Arizona, USA. In addition, samples of Xanthoparmelia spp. from Arizona State University lichen herbarium material (1975-1976) was utilized for a limited number of sites in order to explore temporal trends. The lichen material was cleaned, wet digested and analyzed by ICP-MS for a suite of elemental concentrations [antimony (Sb), cadmium (Cd), cerium (Ce), chromium (Cr), cobalt (Co), copper (Cu), dysprosium (Dy), europium (Eu), gadolinium (Gd), gold (Au), holmium (Ho), lead (Pb), lutetium (Lu), neodymium (Nd), nickel (Ni), palladium (Pd), platinum (Pt), praseodymium (Pr), samarium (Sm), scandium (Sc), silver (Ag), terbium (Tb), thulium (Tm), tin (Sn), uranium (U), ytterbium (Yb), yttrium (Y), and zinc (Zn)]. Cluster analysis and principal component analysis suggest three major factors, which, depending on regional aerosol fractionation, explain most of the variation in elemental signatures: (1) a group of widely distributed rare earth elements (2) a highly homogenous Co, Cr, Ni, and Sc component representing the influence of mafic rocks, and (3) anthropogenic emissions. Elemental concentrations in Maricopa County lichens were generally comparable to those reported for relatively unpolluted areas. Only highly urbanized regions, such as the greater Phoenix Metropolitan Area and the NW corner of the county, exhibited elevated concentrations for Zn, Cu, Pb, and Cd. Lead levels in lichens have fallen over the last 30 years by 71%, while Zn concentrations for some regions have increased by as much as 245%. From the spatial pattern of elemental deposition for Cd, Cu, Ni, Pr, Pb, and Cu, we infer that agriculture, mining, industrial activities, and traffic probably are the major air pollutant sources in Maricopa County.

Air Pollutants↗