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Radiofrequency catheter ablation in small children: relationship of complications to application dose.

Little data exists to support the use of procedural modifications during radiofrequency catheter ablation (RFCA) in small children. A single institution database was reviewed for patients under 15 kg undergoing RFCA from January 1998 to August 2001. Of 268 RFCA procedures, 18 were done in 14 patients under 15 kg (median weight 5.7 kg, 3.5-13.7; age 5.8 months, 1.2-19.8). Six patients had normal hearts, 4 had congenital heart disease, and 4 patients had cardiomyopathy. Diagnoses were orthodromic reciprocating tachycardia (ORT) in nine patients/nine studies, chaotic atrial tachycardia (CAT) in one patient/two studies, and VT in four patients/seven studies. RFCA variables included maximum temperature (69 degrees C, 50-78), total applications (10, 2-21), applications > 20 seconds (5, 0-15), and total application time (331 s, 26-1,006 s). Complications were pericardial effusion in 1 patient, mild mitral regurgitation in 1, and myocardial infarction in 1 patient. When indexed for weight, the number of applications with a duration > 20 seconds in the ORT group was significantly greater in complicated versus uncomplicated procedures (0.7 applications/kg vs 0.16 applications/kg, P = 0.05). In addition, for the ORT subgroup, the indexed total application time trended higher in complicated versus uncomplicated procedures (40.6 s/kg, vs 6.6 s/kg, P = 0.1). RFCA success was 9/9 in ORT, 6/7 in VT, and 0/2 in CAT. RFCA can be successful in small children; however, complications appear to be related to RF dose indexed for body size. Thus, the decision to proceed with RFCA, and the application duration and number should be guided by patient size, balanced against the risks of the arrhythmia, and reserved for dire circumstances.

Body Weight↗

Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis.

BACKGROUND/AIMS: Dry skin (xerosis) is a characteristic change associated with atopic dermatitis (AD) and has often been treated with topical petrolatum applications despite its unfavorable feel. Recently, various therapeutically effective skin-care products with better feel have been introduced. To elucidate the mechanisms underlying the clinical effectiveness of these newer treatments, we used our recently established hairless mouse model of AD. METHODS: We produced AD-like skin lesions in hairless mice with repeated applications of 2,4,6-trinitro-1-chrolobenzene (TNCB) in acetone for 36 days as reported previously. Groups of five mice with AD-like skin were treated once daily with an emollient-type cream containing petrolatum, a moisturizer-type cream containing 10% glycerin, a solution of 0.01% dexamethasone in acetone, or were left untreated. Over the duration of these treatments, we conducted non-invasive measurements of skin surface condition with biophysical instruments and electron microscopic evaluation of the surface area size and density of rear surface villi of superficial corneocytes. We also obtained skin biopsy samples and blood samples at each time point for histopathological evaluation and to assess serum IgE levels, respectively. RESULTS: After cessation of topical TNCB applications, AD-like skin underwent spontaneous resolution with normalization of skin appearance. A similar reduction in skin fold thickness was observed in the cream-treated mice and in the untreated mouse group, whereas a significant decrease in skin thickness was observed in the dexamethasone-treated mice. Transepidermal water loss, a measure of stratum corneum barrier function, rapidly normalized in all groups, without any statistical differences noted among groups. In comparison with untreated skin, skin surface hydration markedly improved after repeated applications of the moisturizer-type cream, whereas it consistently remained low in dexamethasone-treated skin. The skin treated with emollient-type cream appeared similar to skin that received no treatment. Reduced corneocyte surface area size resulting from repeated applications of TNCB returned to control size with cream treatments, while the corneocyte surface area size became much larger following dexamethasone treatment. In addition, the density of villi on the rear surface of corneocytes decreased with application of the creams or dexamethasone. By contrast, no changes were observed in the number of leukocytes in the epidermis or in serum IgE levels among the different treatment groups. In all treatment groups, even after 32 days of treatment, reapplication of TNCB resulted in early-stage skin swelling, but only in the steroid-treated animals did this swelling show a remarkably prolonged time course. CONCLUSIONS: Our present results indicate that the efficacy of skin-care products containing no active ingredients in treating atopic xerosis can be objectively evaluated using the hairless mouse model of AD.

Administration, Cutaneous↗

Ground water modeling applications using the analytic element method.

Though powerful and easy to use, applications of the analytic element method are not as widespread as finite-difference or finite-element models due in part to their relative youth. Although reviews that focus primarily on the mathematical development of the method have appeared in the literature, a systematic review of applications of the method is not available. An overview of the general types of applications of analytic elements in ground water modeling is provided in this paper. While not fully encompassing, the applications described here cover areas where the method has been historically applied (regional, two-dimensional steady-state models, analyses of ground water-surface water interaction, quick analyses and screening models, wellhead protection studies) as well as more recent applications (grid sensitivity analyses, estimating effective conductivity and dispersion in highly heterogeneous systems). The review of applications also illustrates areas where more method development is needed (three-dimensional and transient simulations).

Algorithms↗

Antenna arrays in the SIGMA-eye applicator: interactions and transforming networks.

OBJECTIVES: In multiantenna applicators such as the SIGMA-60 or SIGMA-Eye, which consist of 4 or 12 pairs of antennas shunt to 4 or 12 amplifiers ("antenna couplets"), phases and amplitudes in the feed points of these antennas under certain conditions can significantly differ from the values selected at the multichannel amplifier (forward parameters), mainly due to coupling. In the SIGMA-Eye, this interaction is particularly affected by the transforming networks between the generators and the feed points, thus hampering the control of the feed point parameters. In this work, we perform measurements at existing applicators, present a formalism to describe the facts numerically, and investigate modifications of the transforming networks to improve the performance. METHODS AND MATERIALS: We prepared an experimental setup for the SIGMA-Eye applicator that is fed by forward waves of a 12-channel amplifier system. In this setup, we made the water bolus, the interior of the tissue-equivalent phantom, and the entire transforming network accessible for measuring probes. Then, we constructed various alternative transforming networks such as Pawsey loops, LC matching networks, and power dividers and compared them with the original matching network of the SIGMA-Eye applicator. In particular, we utilized a high-resistive probe to determine the disturbances and influences caused by some channels with respect to some selected feed points of the SIGMA-Eye dipoles. RESULTS: In the original SIGMA-Eye applicator, the influences of coupling channels on the phases and voltages in the feed point of a particular antenna are largest for adjacent longitudinal channels. Here, the +/- 10 degrees phase shift and +/- 30% voltage change were observed if the reference channel (i.e., the disturbed channel) and disturbing channel are equally powered. The changes eminently increased to -30 degrees to + 100 degrees phase shift and -80% to +50% voltage change if the reference channel is fed with much lower power (four to eight-fold) than the disturbing channel. The disturbance from distant channels is less but still significant, reaching shifts of -10 degrees to +50 degrees and -50% to +20%, respectively. Using Pawsey loops instead of the original ferrite rings in the SIGMA-Eye network, the efficacy of the baluns was improved by a more than a factor of 4. Using an LC matching network, dependencies on frequency and external arrangements can be reduced significantly. Applying a power divider circuit, the coupling between antennas combined to one channel is considerably diminished (down to <-25 dB). CONCLUSION: Coupling between resonators (pairs of antennas including the matching network) reduces the control of the SIGMA-Eye applicator, i.e., it causes deviations between the selection of forward parameters at the amplifier and the total actual parameters in the feed points of the antennas. Modified transformation networks can improve the control, in particular by reducing sheath currents and asymmetries. There is a linear but variable relationship between selected (amplifiers) and actually given (feed points) parameters. This linear mapping (described by a matrix) and its characteristics need further investigation.

Hyperthermia, Induced↗

SURLAS: a new clinical grade ultrasound system for sequential or concomitant thermoradiotherapy of superficial tumors: applicator description.

A new ultrasound applicator with three-dimensional power distribution control was developed for simultaneous thermoradiotherapy. The system was named SURLAS for Scanning Ultrasound Reflector Linear Arrays System. In this paper, the hardware of the first clinical grade SURLAS applicator is described with emphasis on clinically important static acoustic characteristics and on construction aspects not reported before. Functionally, the SURLAS applicator consists of two parallel opposed ultrasound linear arrays aiming their acoustic beams to a V-shape scanning ultrasound reflector, which deflects the beams coming from opposite directions toward the treatment area. The reciprocating motion of the reflector in-between the arrays spreads the ultrasonic energy over the target area scanned. Control of power deposition over the 16 cm by 16 cm treatment window area is achieved by adjusting the power input into the transducer elements of the arrays as a function of the position of the scanning reflector. Furthermore, the arrays operate at significantly different frequencies (1.9 and 4.9 MHz) so that intensity modulation of beams of different frequencies can be exploited to adjust the depth of energy penetration. With this design, external electron or photon beams can be concurrently delivered with hyperthermia by irradiating through the applicator's body. Safety features were implemented into the applicator's design to monitor its performance during operation. A detailed description of the applicator including impedance matching circuits/filters, radiation force balance power measurements, hydrophone pressure field distribution measurements, as well as safety test results are reported.

Acoustics↗

Multisectored interstitial ultrasound applicators for dynamic angular control of thermal therapy.

Dynamic angular control of thermal ablation and hyperthermia therapy with current interstitial heating technology is limited in capability, and often relies upon nonadjustable angular power deposition patterns and/or mechanical manipulation of the heating device. The objective of this study was to investigate the potential of multisectored tubular interstitial ultrasound devices to provide control of the angular heating distribution without device manipulation. Multisectored tubular transducers with independent sector power control were incorporated into modified versions of internally cooled (1.9 mm OD) and catheter-cooled (2.4 mm OD) interstitial ultrasound applicators in this work. The heating capabilities of these multisectored devices were evaluated by measurements of acoustic output properties, measurements of thermal lesions produced in ex vivo tissue samples, biothermal simulations of thermal ablation and hyperthermia treatments, and MR temperature imaging of ex vivo and in vivo experiments. Acoustic beam measurements of each applicator type displayed a 35 degrees -40 degrees acoustic dead zone between each independent sector, with negligible mechanical or electrical coupling. Thermal lesions produced in ex vivo liver tissue with one, two, or three sectors activated ranged from 13-18 mm in radius with contiguous zones of coagulation between active sectors. The simulations demonstrated the degree of angular control possible by using variable power levels applied to each sector, variable duration of applied constant power to individual sectors, respectively, or a multipoint temperature controller to vary the power applied to each sector. Despite the acoustic dead zone between sectors, the simulations also showed that the variance from the maximum lesion radius with three elements activated is within 4%-13% for tissue perfusions from 1-10 kg m(-3) s(-1). Simulations of hyperthermia with maximum tissue temperatures of 45 degrees C and 48 degrees C displayed radial penetration up to 2 cm of the 40 degrees C steady-state contour. Thermal characterizations of trisectored applicators in ex vivo and in vivo muscle, using real-time MR thermal imaging, reinforced angular controllability and negligible radial variance of the heating pattern from the applicators, demonstrated effective heating penetration, and displayed MR compatibility. The multisectored interstitial ultrasound applicators developed in this study demonstrated a significant degree of dynamic angular control of a heating pattern without device manipulation, while maintaining heat penetration consistent with previously reported results from other interstitial ultrasound applicators.

Animals↗

Improved applicator-patient coupling in microwave-induced hyperthermia.

The effect on the efficiency of power transfer and microwave leakage of different applicator-load coupling schemes is examined. For a 915-mHz applicator and musclelike phantom separated by 4 cm, it is found that by filling the air gap with dielectric powder or deionized water, the efficiency of power transfer from applicator to load can be raised to levels comparable to that obtained for direct applicator-load contact. For these coupling conditions, it is also found that microwave leakage intensities in the immediate vicinity of the applicator-phantom interface can be reduced to direct contact levels. Employment of such materials and techniques in our clinic, for coupling applicators to patient surfaces in the administration of local hyperthermia to head and neck tumors, has facilitated the reduction of average microwave leakage intensities from more than 15 MW/cm2 to less than 3 MW/cm2 in most cases.

Humans↗

Dosimetry of ruthenium-106 eye applicators.

In view of the importance of clinical applications of ruthenium-106 beta-ray sources for the treatment of choroidal melanoma, experimental, and theoretical approaches are presented for the dosimetry of such sources. The absolute dose and percentage depth dose of ruthenium applicators have been measured with an extrapolation ionization chamber. For a special flat applicator the absolute dose could be measured with an accuracy of +/- 5%, which is determined by the collection efficiency of the extrapolation chamber. The percentage depth dose of concave applicators, employed in the clinical situation, could only be measured at a distance larger than 5 mm due to their geometry and the outer dimensions of the extrapolation chamber. A computer simulation was therefore developed for the absorption and scattering of electrons, taking into account the geometry and materials of the applicator, to predict the percentage depth dose at distances smaller than 5 mm. The calculated and experimentally determined depth doses are in good agreement. With the aid of the computer simulation a depth dose determination for concave applicators can be made for clinically relevant distances less than 10 mm from the source surface with an absolute accuracy of +/- 10%.

Beta Particles↗

A model for electron-beam applicator scatter.

Applicators (or cones), used in conjunction with patient specific cutouts in electron-beam radiotherapy, may interact with the primary electron beam to produce a secondary beam component (applicator scatter). This component affects machine output as well as the shape of resulting dose distributions. A model has been developed to simulate this scatter component for applicators consisting of trimming plates of arbitrary shape. This model involves sampling established kernels of scatter from edge elements of appropriate materials, obtained through Monte Carlo simulations. The result of the model is a phase space (position, direction, energy, charge, weighting) of applicator scattered particles which can be incorporated into a further Monte Carlo simulation, or as input into another advanced treatment planning algorithm. This model is evaluated by comparison of measured profiles and applicator scatter component depth dose curves with Monte Carlo simulations using simulated phase-space data as input. Results are very consistent and reveal information on the angular and spatial variation characteristics of this beam component. The results obtained verify the developed model as an accurate predictor of the characteristics of applicator scattered particles.

Computer Simulation↗

Visualization and registration of three-dimensional E-field distributions in annual-phased-array applicators.

A testing system is presented allowing registration, digitization, and evaluation of three-dimensional power distributions rendered by annular-phased-array applicators in homogeneous liquid media. The system is based on a lamp phantom originally developed to visualize power distributions. Now the brightness distribution is registered via a charge-coupled device camera and transferred to a PC-based evaluation system outside the shielding room. An appropriate mechanical coupling of camera and sensor matrix probing the phantom was built in order to keep optical image conditions constant under movement. For visualization and evaluation commercially customized software was employed. The evaluation of the system shows the linearity between sensor signal and power density magnitude to be sufficient for evaluation and graphical representation of three-dimensional data sets. In a first practical application the testing system was employed to evaluate dependencies of power distributions as a function of frequency and phase settings on temperatures and, subsequently, the relevance of those results for clinical hyperthermia in a SIGMA-60 applicator (BSD-2000 system). Now, the system is ready to evaluate more complex multiantenna array applicators like the SIGMA-Eye applicator. The measuring system is particularly suitable for a fast comparison of APA applicators applied for a homogeneous medium. Implications for heterogeneous structures (like in patients) are then possible via modeling calculations.

Calibration↗

Streptococcus sobrinus antigens that react to salivary antibodies induced by tonsillar application of formalin-killed S. sobrinus in rabbits.

We previously found that tonsillar application of antigen induces a strong antibody response to Streptococcus sobrinus in saliva and blood plasma. Rabbits immunized against S. sobrinus by tonsillar application were highly resistant to experimental dental caries triggered by oral inoculation of living S. sobrinus organisms with sucrose. In the present study, we examined the reaction of S. sobrinus antigens to the antibodies induced by the tonsillar application of S. sobrinus AHT-k in rabbits and compared them to those antibodies induced by intramuscular injection. In an enzyme-linked immunosorbent assay using ultrasonic fragments from mutans group streptococci, the saliva and blood plasma selectively reacted to S. sobrinus AHT-k (serotype g) and serologically related streptococci (serotypes a, d, and h) in the sixth week after tonsillar application, whereas the blood plasma in the sixth week after intramuscular injection reacted to the unrelated streptococci (serotypes b, c, e, and f) in addition to the aforementioned streptococci. The antibody reactivity induced after tonsillar application was not lost after treatment of the antigen with heat or proteinase digestion, whereas these treatments resulted in a 70% decrease of the antibody reactivity induced by intramuscular injection. The inhibition by haptenic sugars and the decrease in immunoreactivity by heat treatment and proteinase digestion suggested that 80% of the antibodies induced by tonsillar application reacted to saccharides. These saccharide antigens appeared to be involved in a specific reaction with S. sobrinus-specific streptococci and a selective reaction with serologically related streptococci. These antigens are probably involved in anticaries reactions in experimental dental caries.

Animals↗

Mortality in a cohort of licensed pesticide applicators in Florida.

OBJECTIVES: Although the primary hazard to humans associated with pesticide exposure is acute poisoning, there has been considerable concern surrounding the possibility of cancer and other chronic health effects in humans. Given the huge volume of pesticides now used throughout the world, as well as environmental and food residue contamination leading to chronic low level exposure, the study of possible chronic human health effects is important. METHODS: This was a retrospective cohort study, analysed by general standardised mortality ratio (SMR) of licensed pesticide applicators in Florida compared with the general population of Florida. A cohort of 33,658 (10% female) licensed pesticide applicators assembled through extensive data linkages yielded 1874 deaths with 320,250 person-years from 1 January 1975 to 31 December 1993. RESULTS: The pesticide applicators were consistently and significantly healthier than the general population of Florida. As with many occupational cohorts, the risks of cardiovascular disease and of diseases associated with alcohol and tobacco use were significantly lower, even in the subpopulations--for example, men, women, and licence subcategories. Among male applicators, prostate cancer mortality (SMR 2.38 (95% confidence interval (95% CI) 1.83 to 3.04) was significantly increased. No cases of soft tissue sarcoma were confirmed in this cohort, and non-Hodgkin's lymphoma was not increased. The number of female applicators was small, as were the numbers of deaths. Mortality from cervical cancer and breast cancer was not increased. Additional subcohort and exposure analyses were performed. CONCLUSIONS: Consistent with previous publications on farmers but at odds with current theories about the protective effects of vitamin D, prostate cancer was increased in these pesticide applicators. Female breast cancer was not increased despite theories linking risk of breast cancer with exposure to oestrogen disruptors--such as the organochlorines. The lack of cases of soft tissue sarcoma is at odds with previous publications associating the use of the phenoxy herbicides with an increased risk of these cancers.

Adult↗

Uterine perforation during intracavitary application. Prognostic significance in carcinoma of the cervix.

All cases of uterine perforation occurring during intracavitary application for carcinoma of the cervix over a 13-year period (1968-1981) were reviewed. There were 14 perforations out of 799 applications in 622 patients, for an incidence of 2.25% of patients and 1.75% of applications. In most cases, it is sufficient to halt the application and carefully monitor the patient, as supported by the uneventful post-perforation course in 12 cases. Nine patients (64%) underwent subsequent intracavitary application without further complications; of these, 8 are still living or died without evidence of tumor. In the other 5, it was impossible to locate the cervical canal on subsequent applications. Alternative treatments, results of therapy, and analysis of failures are presented. The authors conclude that there is no direct evidence that uterine perforation alters the prognosis following radiation therapy for carcinoma of the cervix.

Aged↗

Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro.

1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.

Aminooxyacetic Acid↗

Biophysical assessment of persistent effects of moisturizers after their daily applications: evaluation of corneotherapy.

BACKGROUND: Although effective moisturizers can improve xerotic skin changes immediately, their effects are only transient, because the materials applied to the stratum corneum (SC) are easily shed from the skin surface by the daily desquamation process. However, there are a few lines of clinical as well as experimental evidence suggesting that, once application of effective moisturizers is repeated daily, they may produce persistent effects without being influenced by the desquamation of the skin surface. If we can expect such pharmacological effects by simple repeated applications of moisturizers on the skin surface, it will provide a great motivation for the introduction of corneotherapy into the treatment of xerotic skin problems. OBJECTIVE: This study was designed not only to confirm the feasibility of corneotherapy but to propose a practical method to assess such long-lasting effects of moisturizers by using biophysical methods. METHODS: We conducted applications of various moisturizers twice daily to different areas of the flexor surface of the forearms for the initial 5 days of the first week. Thereafter, we performed biophysical measurements of the SC of these areas in the second week, namely 3, 5 and 7 days after their last applications. RESULTS: Daily repeated applications of moisturizers did not induce any change in the water barrier function of the SC or in the size of desquamating corneocytes, a parameter for turnover rate of the SC. However, they substantially increased high-frequency conductance, a parameter for the hydration state of the skin surface, for several days in both normal individuals and patients with atopic xerosis, although the lasting effects were shorter in the latter. The obtained data enabled us to rank the efficacy of moisturizers either according to the duration of the lasting effects or the magnitude of an increase in the hydration levels of the SC. CONCLUSION: The present results confirmed the feasibility of corneotherapy, in which even simple application of moisturizers targeted at the SC can produce unexpected persistent clinical effects after their repeated treatments. The method described in this study constitutes a practical assay system to evaluate the efficacy of topical agents used for dry skin problems objectively and quantitatively.

Adult↗

Effect of intratubular application of angiotensin 1-7 on nephron function.

Cleavage of the C-terminal tripeptide of angiotensin I (Ang I) by neutral endopeptidase 24.11 releases angiotensin 1-7 (Ang 1-7). Because Ang I and neutral endopeptidase 24.11 are present in proximal tubular fluid and brush border, respectively, Ang 1-7 could be released into proximal tubular fluid to affect nephron function. Therefore, we studied the effect of intratubular Ang 1-7 (10(-12) to 10(-8) M) on nephron function employing in vivo renal micropuncture in inactin-anesthetized Munich-Wistar-Frömter rats. We observed that: (i) Intratubular application of Ang 1-7 for 3, 15, or 30 min did not affect reabsorption in the microperfused proximal convoluted tubule determined as net fluid reabsorption. (ii) During perfusion of Henle's loop for 15 min with artificial tubular fluid (time control), we observed a decline in fluid, potassium and sodium reabsorption by 20, 18 and 5%, respectively. A similar decline in reabsorption was seen with intratubular application of Ang 1-7 in a concentration of 10(-12) or 10(-10) M. In contrast, intratubular application of Ang 1-7 in a concentration of 10(-8) M increased fluid, potassium and sodium reabsorption in that nephron segment by 11, 9 and 3%, respectively. The latter response was completely abolished by AT1 angiotensin II receptor antagonist losartan (10[-6] M). (iii) Intratubular application of Ang 1-7 did not affect net sodium, potassium, or fluid reabsorption in the distal tubule. (iv) TGF response assessed by measuring proximal tubular stop-flow pressure or single nephron filtration rate during orthograde open-loop perfusion of Henle's loop was not significantly altered by intratubular application of Ang 1-7. These findings show that intratubular application of Ang 1-7 in concentrations which possibly cover the physiological range does not significantly alter (i) tubular reabsorption in proximal convoluted or distal tubule, or (ii) TGF response. Intratubular Ang 1-7 at a concentration of 10(-8) M appears to increase reabsorption in Henle's loop by an AT1 angiotensin II receptor-mediated mechanism, the physiological relevance of which remains to be established.

Absorption↗

Effect of single and repeated application of chlorhexidine varnish on mutans streptococci in plaque from fissures of premolar and molar teeth.

The aim of this study was to determine the effects of one and two applications of 40% chlorhexidine varnish on the numbers of mutants streptococci in human dental fissure plaques from molar and premolar teeth. Twenty-nine subjects (aged 20-30 years) participated in the study and were randomly assigned to one of three groups. In each subject two fissures with high levels of mutants streptococci were selected. The fissures in group 1 (control group) were treated with placebo varnish containing no chlorhexidine. Fissures in group 2 received a single application of 40% chlorhexidine varnish, whereas fissures in group 3 received an additional chlorhexidine varnish application 1 week after the first application. Fissure plaque samples were taken prior to the first application of chlorhexidine varnish and subsequently 1, 2, and 4 months thereafter. Compared with the fissures in the control group, the suppression of mutans streptococci was significant in plaques from group 2 for up to 2 months and in plaques from group 3 for up to 4 months after application. Mutans streptococci were suppressed more strongly in premolar than in molar teeth and more strongly and for a longer period of time in fissures of premolar teeth treated twice than in fissures of premolars treated once.

Adolescent↗

Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty.

BACKGROUND: In patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty, abciximab reduces major adverse cardiac events (MACE). Clinical trials have studied intravenous administration only. Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective. We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the standard intravenous bolus application. METHODS AND RESULTS: We stratified 403 consecutive patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty according to the type of application of abciximab. A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients. There were no differences between the groups with regard to diabetes mellitus, cardiogenic shock, successful intervention, or preprocedural and postprocedural TIMI flow. At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab (10.2% versus 20.2%; P<0.008), which was independent from stenting in multivariate analysis. The effect was most pronounced in patients with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous 27.5%, P<0.002; n=273). CONCLUSIONS: In patients with acute myocardial infarction or unstable angina undergoing emergency coronary angioplasty, intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the standard intravenous bolus application of abciximab. Prospective, randomized trials are warranted to further assess intracoronary application of abciximab.

Abciximab↗