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Microchip capillary electrophoresis for point-of-care analysis of lithium.

BACKGROUND: Microchip capillary electrophoresis (CE) is a promising method for chemical analysis of complex samples such as whole blood. We evaluated the method for point-of-care testing of lithium. METHODS: Chemical separation was performed on standard glass microchip CE devices with a conductivity detector as described in previous work. Here we demonstrate a new sample-to-chip interface. Initially, we took a glass capillary as a sample collector for whole blood from a finger stick. In addition, we designed a novel disposable sample collector and tested it against the clinical standard at the hospital (Medisch Spectrum Twente). Both types of collectors require < 10 microL of test fluid. The collectors contain an integrated filter membrane, which prevents the transfer of blood cells into the microchip. The combination of such a sample collector with microchip CE allows point-of-care measurements without the need for off-chip sample treatment. This new on-chip protocol was verified against routine lithium testing of 5 patients in the hospital. RESULTS: Sodium, lithium, magnesium, and calcium were separated in < 20 s. The detection limit for lithium was 0.15 mmol/L. CONCLUSIONS: The new microchip CE system provides a convenient and rapid method for point-of-care testing of electrolytes in serum and whole blood.

Antimanic Agents↗

Electron microscopical examination of different aggregation and decomposition states of phosphorylase kinase. Identification and computer averaging of the alpha gamma delta fragment.

A sample of phosphorylase kinase aged by storage was subjected to chromatography on a size exclusion column. Samples from the four major peaks were analysed by electron microscopy. The first major peak consisted of oligomers of the enzyme monomers which showed no structural order. The second peak mainly consisted of dimers of phosphorylase kinase connected to each other by the outer tipes of the "wings", thus identifying a binding locus through cross-labelling. The third peak showed the already known typical forms of phosphorylase kinase ("butterflies", "chalice form"). The last peak yielded structures identical to the alpha gamma delta fragments obtained by lithium bromide cleavage of the intact enzyme. These structures correspond to the curved outer parts of the cup substructures of the chalice and butterfly forms. The result could be verified by computer averaging of the alpha gamma delta fragments. This finding confirms reports (Chan, K.-F. J. & Graves, D.J. (1984) Calcium Cell Funct. 5, 1-31) that the beta-subunits (missing in the distally situated fragment) are located in the central parts of the molecules. The good quality of the averages of the low molecular mass fragment (about 200 kDa) recommends computer averaging of electron micrographs of partial complexes as suitable method for the study of protein complexes.

Bromides↗

The 6 volt battery for implantable cardioverter/defibrillators.

The usage of a 6 V lithium manganese dioxide battery results in a significant reduction of capacitor loading time within implantable defibrillators/cardioverters. In order to provide ERI indication a new cathode formulation has been developed. The battery shows no voltage delays, a low self-discharge and fulfilled all requirements to an energy source for an implantable device.

Defibrillators, Implantable↗

Ziprasidone in bipolar disorder.

Ziprasidone is a second-generation antipsychotic currently marketed for the treatment of schizophrenia and bipolar mania. It has a unique receptor profile that includes high-affinity antagonist activity at 5-hydroxytryptamine (5-HT) 2A, D2, 1D and 2C receptors, a potent agonist activity at 5-HT1A receptors and a relatively high affinity for the 5-HT and noradrenaline transporters. The efficacy of ziprasidone in bipolar mania (current episode, manic or mixed) has been well demonstrated in three placebo-controlled trials. In a three-arm controlled study, ziprasidone was shown to be efficacious in dysphoric mania, whereas haloperidol was comparable to placebo. Open-label treatment for up to 52 weeks supported the sustained efficacy of ziprasidone in bipolar disorder. Combined with lithium, ziprasidone has been shown to be efficacious as an augmenting agent in the acute treatment of mania, with sustained efficacy up to 1 year. Ziprasidone was very well tolerated by patients with bipolar disorder and did not cause increased weight, glucose or lipid levels.

Antimanic Agents↗

The pharmacology of bipolar disorder during pregnancy and breastfeeding.

Treating bipolar disorder in women during reproduction presents a significant challenge to the physician. The pharmaceutical agents most commonly used for treating bipolar disorder have been associated with adverse effects when used during pregnancy and breastfeeding. Of particular concern has been the association of lithium with cardiac malformations, and the association of carbamazepine and valproate with neural tube defects including spina bifida. Toxicity in neonates has also been reported for the most commonly used mood-stabilising agents. Treatment options for mood stabilisation are either associated with risks of adverse events, have been used less frequently and their associated risks are unknown, or may not provide effective prophylaxis against recurrences of bipolar episodes. However, strategies are available that minimise the risk to the fetus and infant whilst still providing effective prophylaxis against bipolar disorder in the mother. Ideally, a treatment regimen tailored to suit the individual should consider both mother and baby and should be planned prior to conception.

Abnormalities, Drug-Induced↗

Insulin-like growth factor I increase glomerular filtration rate and renal plasma flow in man.

Recombinant IGF-I was infused seal at a dose of 20 micrograms-kg 1-h 1 to 2 healthy subjects during a total of 79 h. Serum levels of IGF-I rose from 93 and 177 to 502 and 616 micrograms/l, respectively. Fasting blood glucose remained normal. During the infusion glomerular filtration rate increased by 31%, in subject No. 1 and by 32% in subject No.2. Concomitantly, renal plasma flow increased by 26% and 22%, respectively. Proximal and distal tubular reabsorption of fluid and sodium as determined by lithium clearance was elevated to a similar extent. When determined again one week after the end of the IGF-I infusion, all parameters of renal function had returned to baseline. Sodium excretion, body weight and blood pressure did not change. We conclude that IGF-I infused at pharmacological doses has marked effects on kidney function. Future studies will necessary to define the clinical potential of recombinant IGF-I in the treatment of diseases characterized by impaired renal perfusion and filtration.

Adult↗

Erythrocyte phosphoglucomutase activity of bipolar I patients currently using lithium or carbamazepine.

Lithium has been used for the last five decades to treat bipolar disorder, but the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293 cells, it is inhibited by lithium in the therapeutic concentration range. We measured the phosphoglucomutase activity in erythrocytes and the inhibitor constant for lithium in a population of healthy subjects and compared them to those of bipolar patients treated with lithium or carbamazepine. The specific activity of phosphoglucomutase measured in vitro in erythrocytes from control subjects presented a normal distribution, with the difference between the lowest and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min-1). Comparison of phosphoglucomutase activity in untreated bipolar patients and control subjects showed no significant difference, whereas comparison between bipolar patients treated with carbamazepine or lithium revealed significantly lower mean values in patients treated with carbamazepine (747.3 +/- 27.6 vs 879.5 +/- 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of lithium needed to inhibit phosphoglucomutase activity by 50%, a bimodal distribution among the population tested was obtained. The concentration of LiCl needed to inhibit phosphoglucomutase activity by 50% was 0.35 to 1.8 mM in one group of subjects and in the other it was 3 to 4 mM. These results suggest that phosphoglucomutase activity may be significant in patients with bipolar disorder treated with lithium and carbamazepine.

Adolescent↗

Electron and hole transfer from DNA base radicals to oxidized products of guanine in DNA.

An investigation of electron and hole transfer to oxidized guanine bases in DNA is reported. Guanine in DNA was preferentially oxidized by Br(2)(*-) at 298 K to 8-oxo-7,8-dihydro-guanine (8-oxo-G) and higher oxidation products. HPLC-EC analysis of irradiated DNA shows that the formation of 8-oxo-G could not be increased above the ratio of one 8-oxo-G to 127 +/- 6 bp regardless of dose. 8-oxo-G can be produced only at low levels because it is further oxidized to other species. These oxidation products of guanine have been extensively investigated and identified by others. Our electron spin resonance studies suggest that at 77 K 8-oxo-G is a trap for radiation-produced holes, but certain further oxidation products of 8-oxo-G (G(ox)) are found to be efficient electron traps. Gamma irradiation of oxidized DNA samples in frozen (D(2)O) aqueous ices and glassy 7 M LiBr solutions resulted in radicals formed by electron attachment to the G(ox) sites that were monitored by electron spin resonance spectroscopy (ESR) at 77 K. These ESR spectra suggest that those oxidation products of 8-oxo-G containing alpha-diketo groups account for the electron traps (G(ox)) in oxidized DNA with oxaluric acid a likely major trap. Electron transfer from DNA anion radicals to G(ox) was followed by monitoring of their ESR signals with time at 77 K. Using typical values for the tunneling constant beta estimates of the relative amount of G(ox) to base pairs were obtained. Radicals formed by UV photolysis of oxidized DNA in 8 M NaClO(4) glassy aqueous solutions were also investigated. The 8-oxo-G cation accounts for less than 10% of all the radicals observed after either gamma irradiation of oxidized DNA in frozen (D(2)O) aqueous solution or UV photolysis of oxidized DNA in 8 M NaClO(4) glassy aqueous solutions. We estimate hole transfer distances of about 7 +/- 1 bp at 1 min from G(*+) to 8-oxo-G.

Animals↗

The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder.

OBJECTIVE: To present an economic model and cost-effectiveness estimates for lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes from the pivotal lamotrigine trials. The main comparator treatments in the pivotal trials were lithium and .no maintenance. (acute-only) treatment. A comparison with olanzapine was included as an indirect analysis following publication of data during the course of our research. METHODS: A Markov model was built around the 3 health states of euthymia, mania, and depression. The base-case model simulates a cohort of 1,000 patients with BD-I who have recently stabilized after resolution of a bipolar mania episode. The cohort was modeled for a period of 18 months. Resource-use estimates were derived from best available published data, treatment guidelines, a physician survey, and published unit cost data. Outputs were measured in terms of costs per acute mood episode avoided, costs per euthymic day gained, and costs per quality-adjusted life-years (QALYs). Direct health care payer costs are used in the analyses. RESULTS: The base-case model for patients with a recent manic episode indicated that lamotrigine is the most effective treatment for avoiding both acute depression episodes and all types of acute episodes (depression and mania). It is also the most effective treatment in terms of number of euthymic days achieved (309 days per patient per year). Olanzapine is most effective for avoiding acute mania episodes. Total direct costs of treatment are lowest for the lithium treatment arm (Dollars 8,710 per patient for the 18-month period). All maintenance therapies were cost effective compared with the no-maintenance (acute-only treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided compared with lithium. A QALY analysis indicated that lamotrigine is cost effective in patients with a recent manic episode at Dollars 26,000 per QALY. The base-case model indicated that lamotrigine dominates olanzapine, (that is, lamotrigine costs less and is more effective than olanzapine) in patients with a recent manic episode. In a sensitivity analysis using outcomes from the pivotal trial of recently depressed patients, lamotrigine, in comparison with lithium, was not shown to be as cost effective as in the recently manic patients, but it was still cost effective compared with no maintenance treatment. CONCLUSIONS: For a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that prevention of mood episodes with lithium and lamotrigine is cost effective in patients with a recent manic, mixed, or hypomanic episode. The conclusions with respect to the indirect comparison with olanzapine should be validated if and when direct trial data become available. Cost-effectiveness of maintenance treatments for patients with BD-I (recently depressed as well as recently manic) are likely to improve in models with a broader costing perspective and that take a longer time frame. Further research into the outcome implications of health-related quality of life and other BD subgroups are recommended.

Adult↗

Nitrate removal in riparian wetlands: interactions between surface flow and soils.

Riparian wetlands containing springs are thought to be ineffective at removing nitrate because contact times between the upwelled ground water and the underlying microbially active soils are short. Tracer experiments using lithium bromide (LiBr) and nitrate (NO3-N) injected at the surface were used to quantify residence times and NO3-N removal in a riparian swale characteristic of New Zealand hill-country pasture. An experimental enclosure was used with collecting trays at the downstream end to measure flow and concentration, shallow wells to measure subsurface concentrations, and an array of logging conductivity probes to monitor tracer continuously. The majority of added tracer reached the outlet more slowly than could be explained by surface flow, but more quickly than could be explained by Darcy seepage flow. There was evidence from the wells of tracer diffusing vertically to a depth of at least 5 cm into the surface soil layer, which was permanently saturated and highly porous. During dry weather 24 +/- 9% of added NO3-N was removed over a distance of 1.5 m largely by denitrification. The net uptake length coefficient for this wetland (K = 0.08 +/- 0.03 m(-1)) is slightly higher than the range (K = 0.01-0.07 m(-1)) measured in a small stream channel infested with macrophytes. Nitrate removal is expected to decrease with increasing flow. Seepage flow is estimated to have removed only 7 +/- 4% of the added NO3-N and we hypothesize that vertical diffusion substantially increases NO3-N removal in this type of wetland. Riparian wetlands with springs and surface flows should not be dismissed as having low NO3-N removal potential without checking whether there is significant vertical mixing.

Bromides↗

Long term treatment of bipolar disorder.

Bipolar disorder is characterised by recurrent episodes of mania and depression. The major objective of long term treatment is to reduce the frequency of these episodes. Lithium is the most widely recommended drug for this purpose, having been shown in controlled clinical trials to be more effective than placebo in reducing the likelihood of relapse. Unfortunately, its effectiveness in clinical practice is less than that predicted from these trials. A major cause of relapse is noncompliance, largely due to intolerance to adverse effects such as perceived mental sluggishness, thirst, polyuria and weight gain. Regular monitoring of lithium plasma concentrations is required to ensure that the range of 0.5 to 0.9 mmol/L is not exceeded. Concentrations above this can lead to toxic symptoms, which if unchecked can cause brain damage and even death. The anticonvulsant drugs carbamazepine and valproic acid (sodium valproate) are potential alternatives to lithium. Patients who relapse frequently despite lithium may benefit from the addition of one of these agents, although formal clinical trial evidence of the efficacy of such combination treatment is lacking. Antipsychotics, administered as a depot formulation, can reduce the likelihood of relapse in patients with frequent manic episodes, especially if associated with poor compliance. Psychological treatment and patient education have been shown to improve outcome, and should be made more widely available to all patients with bipolar disorder.

Anticonvulsants↗

Polymerization efficiency of different photocuring units through ceramic discs.

This study compared the ability of a variety of light sources and exposure modes to polymerize a dual-cured resin composite through ceramic discs of different thicknesses by depth of cure and Vickers microhardness (VHN). Ceramic specimens (360) (Empress 2 [Ivoclar Vivadent], color 300, diameter 4 mm, height 1 or 2 mm) were prepared and inserted into steel molds according to ISO 4049, after which a dual-cured composite resin luting material (Variolink II [Ivoclar Vivadent]) with and without self-curing catalyst was placed. The light curing units used were either a conventional halogen curing unit (Elipar TriLight [3M/ESPE] for 40 seconds), a high-power halogen curing unit (Astralis 10 [Ivoclar Vivadent] for 20 seconds), a plasma arc curing unit (Aurys [Degré K] for 10 seconds or 20 seconds) or different light emitting diode (LED) curing units (Elipar FreeLight I [3M/ESPE] for 40 seconds, Elipar FreeLight II [3M/ESPE] for 20 seconds, LuxOmax [Akeda] for 40 seconds, e-Light [GC] for 12 seconds or 40 seconds). Depth of cure under the ceramic discs was assessed according to ISO 4049, and VHN at 0.5 and 1.0 mm distance from the ceramic disc bottom was determined (ISO 6507-1). Medians and the 25th and 75th percentiles were determined for each group (n=10), and statistical analysis was performed using the Mann-Whitney-U-test (p < or = 0.05). The results showed that increasing ceramic disc thickness had a negative effect on the curing depth and hardness of all light curing units, with hardness decreasing dramatically under the 2-mm thick discs using LuxOmax, e-Light (12 seconds) or Aurys (10 seconds or 20 seconds). The use of a self-curing catalyst is recommended over the light-curable portion only, because it produced an equivalent or greater hardness and depth of cure with all light polymerization modes.

Ceramics↗

Surface roughness in ceramics with different finishing techniques using atomic force microscope and profilometer.

This study assessed the finishing and polishing of 3 ceramic materials: Vitadur Alpha, IPS Empress 2 and AllCeram. Surface modification techniques were selected to simulate dental practice. Forty-five specimens of each ceramic were divided into 5 groups of 9 specimens, which were finished using the following procedures: Group 1--glaze; Group 2--glaze, grinding and subsequent polishing with the Eve system; Group 3--glaze, grinding and subsequent polished with the Identoflex system; Group 4--glaze followed by polishing with Identoflex; Group 5--glaze, grinding and subsequent polishing with Shofu kit. Two roughness-measuring instruments were used: a stylus profilometer and an atomic force microscope (AFM). The 135 specimens were evaluated quantitatively with respect to Ra (average roughness) and Ry (maximum roughness height), and the results were examined statistically by ANOVA and Tukey's test, with a significance level of 0.05. The roughness parameter (Ra), measured by the profilometer, and AFM showed that some of the commercial intraoral polishing kits tested achieved a finish equal in smoothness to the glazed surface. According to Pearson's test, no correlation was found between the parameter Ry, measured with the profilometer, and AFM. The profilometer results for Ry demonstrated no significant differences between the final polished surfaces and the initial glazed ones. On the other hand, the Ry values obtained by AFM indicated the tested polishing kits incapability of producing smoothness comparable to the glazed surfaces.

Aluminum Oxide↗

High-power lithium-ion.

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Biomedical Engineering↗

The IAEA/WHO TL dosimetry service for radiotherapy centres 1969-87.

The International Atomic Energy Agency (IAEA) started a postal dosimetry service in 1966 using lithium fluoride (LiF) thermoluminescent dosimeters (TLD). The World Health Organization (WHO) joined the programme in 1968. Dosimeters were sent on 29 occasions to primary standards laboratories or to the 'Bureau International des Poids et Measures' to guarantee the traceability to primary standards of absorbed dose. The mean deviation was -0.26 +/- 0.18% (1% SD of the mean). One SD for a single result was about 1%. The number of intercomparisons made during the whole period is about 2,000 from about 700 radiotherapy centres in 89 countries. To date only 60Co machines have been included. The mean deviation of all the results from the centres was -0.25, and 1% SD for a single result 6.7%. About 5% of the centres had deviations larger than 30%, at least on one occasion. It is shown that the accuracy in dosimetry improves considerably for those departments participating more than once in the TL dosimetry service.

Calibration↗

Energy response of a thermoluminescent lithium fluoride disc dosimeter to beta-rays.

In order to eliminate some drawbacks of thin detector with suitable window for measuring radiations of low penetrating power, the thermoluminescent LiF disc dosimeter was fabricated from phosphor of LiF with activators of magnesium and copper and inorganic binder of silica and alumina. The energy response of the LiF disc dosimeters to beta-rays was investigated by comparing with theoretical calculations and measurements with a parallel-plate ionization chamber. From the results obtained, the LiF disc dosimeter significantly underestimated the doses for low beta-ray energy (below 0.3 MeV), while its reading agreed well with the calculated ones for high energy (above 0.8 MeV). Nevertheless, it is suggested that the fabricated LiF disc dosimeter is useful to evaluate the skin dose from the practical point of view, since beta-ray less than 0.6 MeV is completely absorbed before reaching the skin covered with clothing.

Beta Particles↗