Efficacy and safety of methantheline bromide (Vagantin(®) ) in axillary and palmar hyperhidrosis: results from a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Focal hyperhidrosis can severely affect quality of life. So far, knowledge on the effect of systemic therapy of focal hyperhidrosis is limited. OBJECTIVE: To assess the efficacy and safety of methantheline bromide (MB) in the treatment of axillary and palmar-axillary hyperhidrosis. METHODS: A multicenter controlled randomized double-blind clinical trial was conducted in patients with axillary or palmar-axillary hyperhidrosis defined by a sweat production >50 mg/5 min. Patients received 3 × 50 mg MB daily or placebo over a period of 28 ± 1 days. Main outcome criterion was the reduction of sweat as measured by gravimetry on day 28 ± 1. Quality of life was assessed by Dermatology Life Quality Index (DLQI) and Hyperhidrosis Disease Severity Score (HDSS). RESULTS: A total of 339 patients were randomly assigned to receive MB or placebo. On day 28 ± 1, the mean axillary sweat production was 99 mg for MB and 130 mg for placebo compared with 168 mg and 161 mg respectively at baseline (P = 0.004). Patient's HDSS score decreased in the MB group from 3.2 to 2.4 compared with 3.2 to 2.7 for placebo (P = 0.002). Similar results could be obtained for the DLQI with 9.7 for MB and 12.2 for placebo, which decreased from 16.4 or 17 respectively (P = 0.003). Tolerability was good for both groups. The most frequent adverse event was dry mouth. CONCLUSION: Fifty milligrams methantheline bromide three times a day is an effective and safe treatment of axillary hyperhidrosis.

Orthodontic treatment acceleration with corticotomy-assisted exposure of palatally impacted canines.

OBJECTIVE: To evaluate the effectiveness of a new surgical technique in the treatment of palatally impacted canines. MATERIALS AND METHODS: Six consecutive patients presenting with bilaterally impacted canines were compared. One canine was surgically exposed using a conventional surgical technique while the contralateral canine was exposed using a corticotomy-assisted technique. RESULTS: After tooth movement was completed, statistical comparisons of the two methods revealed a reduction of treatment time of 28-33% for the corticotomy-assisted canines. No significant differences were observed in final periodontal condition between the canines exposed by these two methods. CONCLUSION: This preliminary study supports the concept that a corticotomy-assisted surgical technique helps reduce orthodontic treatment time for palatally impacted canines.

Kinetic evidence that arachidonate-induced calcium efflux from platelet microsomes involves a carrier-type ionophoric mechanism.

Arachidonate, at concentrations up to 50 microM, induced dose-dependent calcium efflux from preloaded microsomes prepared from human platelets, but not from unilamellar egg phosphatidylcholine vesicles. Arachidonate-induced efflux from microsomes was not inhibited by indomethacin, 13-azaprostanoic acid, or catalase and superoxide dismutase, indicating that the release was due to arachidonate and not a metabolite. Linolenate (18:3, cis) and linoleate (18:2, cis) induced calcium efflux in a manner similar to arachidonate (20:4, cis), while arachidate (20:0), linolelaidate (18:2, trans), elaidate (18:1, trans), oleate (18:1, cis), stearate (18:0) and palmitate (16:0) had no effect. An experimental method was developed for distinguishing between carrier ionophore, small aqueous pore (i.e., calcium channel), or large aqueous pore (i.e., detergent effect) mechanisms in vesicular efflux systems in which calcium efflux occurs over a period of minutes. This development predicted that with a carrier ionophore mechanism, an increase in either internal or external calcium should competitively inhibit 45Ca efflux. In contrast, 45Ca efflux by diffusion through a small aqueous pore or a large aqueous pore should be measurably insensitive to variations in internal or external calcium. These predictions were experimentally verified in the platelet microsomal system using efflux agents with known mechanisms. Efflux of 45Ca by A23187, a calcium ion carrier ionophore, was sensitive to internal or external calcium competition, while alamethicin, a small aqueous pore channel model, and Triton X-100, a detergent which forms large aqueous pores, mediated 45Ca efflux which was measurably insensitive to variations in internal or external calcium concentration. Arachidonate-induced 45Ca efflux was inhibited by increasing either internal and external calcium concentration, suggesting that the fatty acid functions as a carrier ionophore. Arachidonate-induced 45Ca efflux was also inhibited with extravesicular Sr2+, but not Mn2+ or Ba2+. The dependence of the initial arachidonate efflux rate on arachidonate concentration showed that at least two arachidonates were contained in the calcium-carrier complex. These results are consistent with a model in which arachidonate (A) and an endogenous microsomal component (B) translocate calcium across the membrane through a carrier ionophore mechanism as part of a complex with a stoichiometry of A2B.Ca.

Randomised double-blind comparison of simethicone with cisapride in functional dyspepsia.

AIM: To compare the efficacy of simethicone with cisapride in patients with functional (non-ulcer) dyspepsia. METHODS: After standardized diagnostic work-up and at least 6-days wash-out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19-71 years) were randomized and treated using a double-dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as 'very good', 'good', 'moderate' or 'no effect'. RESULTS: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Delta30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Delta10.2%, P=0.11). CONCLUSIONS: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.

Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo.

Constant potential amperometry (CPA) was used for in vivo recording of extracellular dopamine (DA) after electrical stimulation of the medial forebrain bundle (MFB) (4 pulses, 2 mA, 20 or 100 Hz) in the striatum of the rat brain. CPA signals were analysed in the absence and presence of the DA uptake inhibitor nomifensine with the help of a mathematical model which considered both the influence of DA diffusion after its stimulated release and the Michaelis-Menten kinetics of cellular DA uptake from the extracellular space. We found an excellent conformity of experimentally obtained CPA signals and calculated curves. Mathematical analysis revealed that CPA signals were strongly influenced by DA diffusion. The kinetic parameters calculated from CPA signals in this study were in agreement with experimental determinations of Vmax and Km of extracellular DA uptake in other studies and reflect the particular pharmacological properties of nomifensine. CPA is a useful and efficient method for in vivo estimation of individual changes of DA kinetic parameters by pharmacological treatment.

Influence of topical metal binding substances, vehicles, and corticosteroid creams on the allergic patch test reaction in metal-sensitive patients.

Persons known to be allergic to nickel, cobalt, or both were patch tested with serial dilutions of cobalt chloride or nickel sulfate either in petrolatum on skin treated with topical preparations with and without metal-binding compounds or incorporated into such special preparations. A decreased response was found in patients tested with Vioform (clinquinol) and cobalt chloride simultaneously, whereas rutin (3,3',4',5,7-pentahydroxyflavon 3-rhamnoglucosid) increased the response, and polyfloretin phosphate had no effect. The vehicles proved significant: "Ung Merck" and "W/O Cream Base" increased reactivity, whereas polyethylene glycol gave good protection against metal ions. As expected, corticosteroid creams suppressed the inflammatory response.

Decline of caries prevalence after the cessation of water fluoridation in the former East Germany.

In contrast to the anticipated increase in dental caries following the cessation of water fluoridation in the cities Chemnitz (formerly Karl-Marx-Stadt) and Plauen, a significant fall in caries prevalence was observed. This trend corresponded to the national caries decline and appeared to be a new population-wide phenomenon. Additional surveys (N=1017) carried out in the formerly-fluoridated towns of Spremberg (N=9042) and Zittau (N=6232) were carried out in order to support this unexpected epidemiological finding. Pupils from these towns, aged 8/9-, 12/13- and 15/16-years, have been examined repeatedly over the last 20 years using standardised caries-methodological procedures. While the data provided additional support for the established fact of a caries reduction brought about by the fluoridation of drinking water (48% on average), it has also provided further support for the contention that caries prevalence may continue to fall after the reduction of fluoride concentration in the water supply from about 1 ppm to below 0.2 ppm F. Caries levels for the 12-year-olds of both towns significantly decreased during the years 1993-96, following the cessation of water fluoridation. In Spremberg, DMFT fell from 2.36 to 1.45 (38.5%) and in Zittau from 2.47 to 1.96 (20.6%). These findings have therefore supported the previously observed change in the caries trend of Chemnitz and Plauen. The mean of 1.81 DMFT for the 12-year-olds, computed from data of the four towns, is the lowest observed in East Germany during the past 40 years. The causes for the changed caries trend were seen on the one hand in improvements in attitudes towards oral health behaviour and, on the other hand, to the broader availability and application of preventive measures (F-salt, F-toothpastes, fissure sealants etc.). There is, however, still no definitive explanation for the current pattern and further analysis of future caries trends in the formerly fluoridated towns would therefore seem to be necessary.

Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens)--improvement of wound healing by autologous epidermal grafts on an esterified hyaluronic acid membrane.

Epidermolysis bullosa dystropicans of the Hallopeau-Siemens type (HS-EBD) is an autosomal-recessive blistering disease. Skin fragility due to mutations in structural proteins is responsible for further development of chronic and painful wounds, skin infections and sepsis. There is no causative treatment available. We present a case report with HS-EBD and longstanding painful wounds treated with autologous keratinocytes on an esterified hyaluronic acid membrane. Two out of three wounds treated showed a complete take of the graft. They improved markedly with a stable result over 12 months until now. Even autologous keratinocyte grafting may have a beneficial effect on chronic wounds in HS-EBD despite the fact that the genetic defects are unchanged.

The cervical facebow and mandibular rotation.

The purpose of this longitudinal investigation was to determine whether the cervical facebow treatment affected mandibular rotation. Pretreatment and posttreatment tracings were compared using four different methods of superimposition in the headgear group and the control group. Mandibular rotation was measured in parameters of direction and intensity. Statistical evaluations of the data were made to determine significant differences between headgear and control groups. The following conclusions can be made: (1) There is a significant difference among the four methods of cephalometric superimposition. (2) The sella-nasion and registration point methods showed a significant difference in mandibular growth direction and intensity between the headgear and the control cases while the intersection and C.C. methods did not.

[Comparative epidemiologic study of caries in German and Hungarian adolescents]. / Német és magyar serdülókorú fiatalok összehasonlító caries epidemiológiai vizsgálata.

The aim of the study was to assess the trend of caries prevalence in German and Hungarian population sample. The authors examined 15-16-year-old Hungarian adolescents in Debrecen and Budapest in 1997 (451 persons), then re-examined them in 1999 (377 persons). These data were compared to those of 15-16 and 17-18-year-old adolescents examined in the Eastern part of Germany (Plauen) in 1991 (668 persons) and in 1995 (586 persons). The results showed significant caries reduction in Germany. The DMFT values of 17-18-year-old adolescents were nearly half in Germany (x = 5.2) compared to those of Hungary (x = 9.0). This fact suggests the necessity of introduction of effective preventive programs including salt fluoridation in Hungary.

The Widom-Rowlinson mixture on a sphere: elimination of exponential slowing down at first-order phase transitions.

Computer simulations of first-order phase transitions using 'standard' toroidal boundary conditions are generally hampered by exponential slowing down. This is partly due to interface formation, and partly due to shape transitions. The latter occur when droplets become large such that they self-interact through the periodic boundaries. On a spherical simulation topology, however, shape transitions are absent. We expect that by using an appropriate bias function, exponential slowing down can be largely eliminated. In this work, these ideas are applied to the two-dimensional Widom-Rowlinson mixture confined to the surface of a sphere. Indeed, on the sphere, we find that the number of Monte Carlo steps needed to sample a first-order phase transition does not increase exponentially with system size, but rather as a power law τ α V(α), with α≈2.5, and V the system area. This is remarkably close to a random walk for which α(RW) = 2. The benefit of this improved scaling behavior for biased sampling methods, such as the Wang-Landau algorithm, is investigated in detail.

Force-induced structural transitions in cross-linked DNA films.

We report on the preparation and characterization of wet-spun films of sodium DNA in which intermolecular cross-links were introduced following formaldehyde treatment. Raman scattering shows that the DNA in moderately cross-linked films is mainly in the B conformation. Stretching experiments show a transition from plastic to elastomeric behavior with increasing exposure to the cross-linking agent. Elastomeric DNA films are strongly disordered. X-ray diffraction shows that stretching of moderately cross-linked films under controlled high humidity conditions results in increased molecular orientation as well as the appearance of meridional reflections at 7.4-7.8 and 8.2 angstroms. These reflections are not observed for any of the classical conformations associated with mixed sequence DNA, and may arise from extended base-pair stacking in a stretched DNA structure.

Multivariate statistical analysis of metal concentrations in teeth of residents of Silesian region, southern Poland.

Concentrations of 11 metals (Cd, Cr, Cu, Fe, Mn, Pb, Zn, Na, K, Ca, and Mg) were assayed in the teeth of two populations of the Silesian region. The first group (n = 83) comprised the residents of Katowice-Szopienice, a town located in the center of the Upper Silesian industrial region, in close proximity to a Pb plant, whereas the other was a group of residents of the agricultural community Strumien (n = 44). The concentrations of all the trace metals were found to be higher in the teeth of Katowice-Szopienice residents. The methods of cluster analysis distinguished two clusters of metals in the teeth: essential (Ca, Na, Mg, Zn, and K) and trace (Cd, Mn, Cr, Cu, Fe, and Pb) elements. Euclidean distances reflected the differences in concentrations between the two groups. The results obtained were analyzed using principal component analysis. Four principal factors accounted for 68.1% of the total variance for Katowice-Szopienice residents and for 80.1% for Strumien residents. The first factor showed high contributions of Cu and Cr, elements present in humans as a result of diet, and also Mn for Katowice-Szopienice residents because of environmental contamination. The second factor was characterized by large Zn and Cd fractions and, for Katowice-Szopienice residents, Pb and K as well. The diversified exposure of both populations was reflected by the differences in Euclidean distances and contribution of particular elements with respect of principal components.

On the energy dissipation in a tank-treading human red blood cell.

The energy dissipation in the membrane (ED mem) and in the cytoplasm (ED cyt) of tank-treading human red blood cells is estimated. The tank-tread motion of the membrane occurs when the cells in a sheared suspension assume a steady-state of orientation (Fischer et al., 1978, Science [Wash. D. C.], 202:894). The kinematic data used are from red cells suspended either in a dextran-saline solution at a low hematocrit, or in plasma at a hematocrit of 45%. The viscosities of the cytoplasm and the membrane are taken from the literature. The cell in dextran was subjected to seven different shear rates. Both ED mem and ED cyt showed a strong increase with shear rate. Their ratio, however, was always of the order of 1. From this value and the value which was given by Hochmuth et al. (1979, Biophys. J., 26:101) for a shape recovery of a red cell, it is concluded that the range of ED mem/ED cyt for all possible geometries is 1-100.

Rise and fall of caries prevalence in German towns with different F concentrations in drinking water.

The rise and fall of caries prevalence (DMFT) and its relation to changing F concentration of drinking water and other health-related factors is analysed based on dental findings of more than 286,000 subjects of either sex (6-15 years old) from the two industrial towns Chemnitz and Plauen. Water fluoridation (1.0 +/- 0.1 ppm F) was implemented in Chemnitz (formerly Karl-Marx-Stadt) in 1959. It was in operation until autumn 1990 with an interruption lasting 22 months around the year 1971. In the F-poor town of comparison, Plauen, 55% of the citizens were supplied with F-enriched drinking water (0.9 ppm F) during the years 1972-1984. Another 20% received F-containing mixed water (0.4-0.7 ppm F). During the first three decades of the study the level of caries prevalence was strictly correlated with the availability of an optimal caries preventive F concentration in the drinking water. Water fluoridation was followed by a decrease of caries, and interruptions in fluoridation were followed by increasing caries levels. A different caries trend was observed in the years from 1987 to 1995. There was a significant caries decrease down to the lowest DMFT (2.0) since 1959 in spite of the fact that only F-poor water was available over years in both towns. This improvement of oral health is explained by changes in caries-preventive and environmental conditions.