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Sufficient post-marketing surveillance is necessary for safety monitoring of vaccines. In this respect the spontaneous reporting system of reporting suspected adverse drug reactions (ADR) following vaccination is an essential tool for safety monitoring. The marketing authorization holder and/or pharmaceutical manufacturer has the legal obligation to report suspected adverse drug reactions (German Drug Law and European Regulation). In addition physicians and traditional healers have to report suspected cases of complications after immunizations pursuant to the German Infection Protection Act (Infektionsschutzgesetz, IfSG). The reports are medically assessed and stored in a database at the Paul Ehrlich Institute. For the publication referenced here, all reported suspected cases of adverse drug reactions after immunizations were evaluated for the period from January 1, 2004-December 31, 2005 according to different criteria. In 2004 (2005) a total of 1237 (1393) suspected cases of adverse drug reactions or suspected complications after immunizations were notified. 858 (919) of these adverse drug reactions (ADR) were serious (69 % and 66 %, respectively). 414 (517) of the ADRs (i.e. 33 % and 37 %, respectively) were reported by physicians according to the IfSG; the other reports were from industry and other reporting sources. 251 (229) i.e. 61 % (44 %) of these reactions were serious. The total number of reports divided by the total number of vaccine doses launched on the German market during the observation period (according to the data provided by the pharmaceutical industry) revealed an overall "reporting rate" of approx. 3 reports per 100,000 vaccine doses. The age groups with the highest absolute number of reported cases were infants and young children (0-2 years), and adults (18-59 years) accounting for approx. one third each of the reports. The age distribution of the suspected cases was comparable with that of previous years. In both years, approx. half of all suspected adverse drug reactions following immunization were of transient nature, i.e. there was a complete recovery (restitution ad integrum). In both years, a very small proportion of cases were reported as permanent damage (30 and 34 cases respectively; 2.4 % of all cases) or resulted in death (35 or 23 cases, respectively; 2.8 % or 1.7 %, respectively). With a few exceptions these adverse events were considered to be related to other diseases and unlikely related to vaccination. Overall, the association between vaccination and adverse events was assessed by the PEI as "possible" in 58 % (62 %) of all cases, respectively, as "likely" in 6 % (8 %) of all cases, and as "certain" in 0.4 % (0.6 %) of all cases. In 14 % (13 %) of the cases, the causal relation was stated as "unlikely". In 17 % (15 %) of all cases, a scientific evaluation was not possible on the basis of the data provided. A separate analysis of reports was conducted for all suspected adverse drug reactions following varicella immunization. According to these data varicella vaccination is considered to be well tolerated. With the exception of an increase in local reactions following pneumococcal polysaccharide vaccination no new safety signal has been recognised during the observation period.

The aim of this paper is to report the oral signs and symptoms of four patients with Kabuki syndrome. All had oral abnormalities affecting the palate, teeth, and/or lips, including wide spacing between the teeth, screwdriver-shaped upper incisors, hypodontia, delayed tooth eruption, narrow spacing in the upper canine area, large pulp chambers of the upper incisors and permanent molars, external root resorption of the upper central incisors and permanent molars, a division of the lower third of the root canal in normally one-rooted teeth, tooth retention, retrognathia of the upper jaw, a high palate or cleft lip/palate, and microforms of lower lip fistula.

We examined major element compositions, carbon and oxygen isotopic compositions, and macro/microffabrics of a 15–30 cm thick, bedded dolostone unit in the upper part of the Elwren Formation in southern Indiaan for evidence of the dolostone’s origin, early alteration, and burial diagenesis. Burial diagenetic alteration of the bedded dolostone and associated nodules is indicated by the presence of recrystallized dolomite with light oxygen isotopic compositions. However, the Elwren Formation dolostones from different outcrops exhibit similar, systematic, straitigraphic trends of key primary microfabrics, organic matter content, carbon and oxygen isotopic compositions, and major element compositions. Therefore, the oxygen isotopic shift caused by burial diagenesis is inferred to have affected the dolostones in a uniform manner so as to preserve relative, primary, oxygen isotopic differences between different parts of the dolostone system. This permits our use of the isotopic data to suggest the processes of formation of the bedded dolostone and the nature of the early alteration of the dolostone.

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

For several years Nonnucleoside reverse transciptase inhibitors (NNRTIs) in antiretroviral therapy have been associated with hepatic side effects. Particularly the hepatotoxic potential of Nevirapine is well analysed today. We performed a prospective, multicenter study to compare the hepatotoxicity of Efavirenz (EFV) with that of Nevirapine (NVP) and to investigate further risk factors.The study included HIV-1-infected patients from five clinics and private medical practices in southwestern Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001. Among 296 patients in total, 151 received EFV and 145 received NVP. Laboratory tests during the course of treatment included liver enzymes, HIV-RNA and CD4 cell-count. Additionally, signs of clinical hepatitis were recorded. Hepatotoxicity was graded in the manner of Sulkowsky et al. (2000), who used a scale modified from that of the AIDS Clinical Trials Group.Hepatitis C virus and hepatitis B virus were detected in 10.1% and 4.1% of patients, respectively. The overall rate of severe hepatotoxicity (grade 3 to 4 elevations in aspartate aminotransferase and/or alanine aminotransferase) was 2 of 151 (1.3%) in patients prescribed EFV and 3 of 145 (2.1%) in patients prescribed NVP. Mild-to-moderate hepatotoxicity (grade 2 elevation) was observed in 6.0% (EFV) and 3.4% (NVP) of patients. Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups. 3 of 14 patients (2.1%) with grade 2 elevation of liver enzymes (LEE) and 4 of 5 patients (80%) with grade 3 to 4 LEE were symptomatic. Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection.Increases of liver enzymes during therapy with NVP or EFV are not unusual, but are mostly mild-to-moderate and asymptomatic. LEE occurs just as frequent in patients prescribed EFV as in patients prescribed NVP.

Sufficient post-marketing surveillance is necessary for safety monitoring of vaccines. In this respect the spontaneous reporting system of reporting suspected adverse drug reactions (ADR) following vaccination is an essential tool for safety monitoring. The marketing authorization holder and/or pharmaceutical manufacturer has the legal obligation to report suspected adverse drug reactions (German Drug Law and European Regulation). In addition physicians and traditional healers have to report suspected cases of complications after immunizations pursuant to the German Infection Protection Act (Infektionsschutzgesetz, IfSG). The reports are medically assessed and stored in a database at the Paul Ehrlich Institute. For the publication referenced here, all reported suspected cases of adverse drug reactions after immunizations were evaluated for the period from January 1, 2004-December 31, 2005 according to different criteria. In 2004 (2005) a total of 1237 (1393) suspected cases of adverse drug reactions or suspected complications after immunizations were notified. 858 (919) of these adverse drug reactions (ADR) were serious (69 % and 66 %, respectively). 414 (517) of the ADRs (i.e. 33 % and 37 %, respectively) were reported by physicians according to the IfSG; the other reports were from industry and other reporting sources. 251 (229) i.e. 61 % (44 %) of these reactions were serious. The total number of reports divided by the total number of vaccine doses launched on the German market during the observation period (according to the data provided by the pharmaceutical industry) revealed an overall "reporting rate" of approx. 3 reports per 100,000 vaccine doses. The age groups with the highest absolute number of reported cases were infants and young children (0-2 years), and adults (18-59 years) accounting for approx. one third each of the reports. The age distribution of the suspected cases was comparable with that of previous years. In both years, approx. half of all suspected adverse drug reactions following immunization were of transient nature, i.e. there was a complete recovery (restitution ad integrum). In both years, a very small proportion of cases were reported as permanent damage (30 and 34 cases respectively; 2.4 % of all cases) or resulted in death (35 or 23 cases, respectively; 2.8 % or 1.7 %, respectively). With a few exceptions these adverse events were considered to be related to other diseases and unlikely related to vaccination. Overall, the association between vaccination and adverse events was assessed by the PEI as "possible" in 58 % (62 %) of all cases, respectively, as "likely" in 6 % (8 %) of all cases, and as "certain" in 0.4 % (0.6 %) of all cases. In 14 % (13 %) of the cases, the causal relation was stated as "unlikely". In 17 % (15 %) of all cases, a scientific evaluation was not possible on the basis of the data provided. A separate analysis of reports was conducted for all suspected adverse drug reactions following varicella immunization. According to these data varicella vaccination is considered to be well tolerated. With the exception of an increase in local reactions following pneumococcal polysaccharide vaccination no new safety signal has been recognised during the observation period.

The width of the gate recess was found to greatly effect the linearity of GaAs MESFETs under class AB operation at 850 MHz. The MESFETs with gate-recess spacing larger than 105 nm exhibit poor 3rd order intermodulation and significantly different 5th order intermodulation product dependence on the output power. Good correlation of the discrete device data with the digital amplifier circuit performance was obtained. This work provides insight into a critical parameter for optimum performance of high linearity amplifier applications.

The filtration system investigated in this study uses the thermic convection caused by radiators for the adsorption of airborne particles. The effect of this filtration system on the reduction of clinical symptoms of allergic bronchial asthma was tested as well as its capability in retaining airborne allergens, in particular those of the house dust mite Dermatophagoides pteronyssinus (D. pter.), which are responsible for this special kind of asthma. Dust samples were taken before and after the heating season in households of 36 persons with D. pter. caused asthma. Their mite content was investigated using mite flotation and direct microscopy, their guanine content using the Acarex-test. An allergen extract obtained from the filters was tested on its allergen content by RAST-inhibition. It could be observed that compared to the preceding heating season 55% of the volunteers felt an improvement of their asthmatic symptoms. It was possible to extract allergens of D. pteronyssinus, house dust and mould from the filters. All these results show the capability of the filters to adsorb house dust mite (HDM) allergens.

In this multicenter case-control study (1,079 melanoma patients, 778 control persons), the significance of the well-known risk factors for the development of malignant melanoma (MM) was assessed for a German population. The multifactorial analysis of the data confirmed the total number of melanocytic nevi (MCN) as the most robust indicator for an increased melanoma risk. For persons with more than 50 MCN the relative risk was 4.8 times as high as for persons with fewer than 10 MCN. Hair color was found to be another valuable indicator. In persons with red hair the risk of MM was 4.7 that in individuals with black hair. Remarkably fair persons with skin type 1 (always sunburn, never tanning) had two times the risk of that in persons with skin type 4 (never sunburn, always tanning). The habit sun bathing for recreation showed no influence on the development of melanoma. A 2.7 x increased melanoma-risk was detected in persons with occupational sun exposure and out of doors work.

During the course of field work for the invertebrate paleontology class at Bucknell University, part of an articulated polyplacophoran was discovered. Because these fossils are rare and because there are only two reports of North American Devonian polyplacophorans (Smith and Hoare, 1987), it is felt that this specimen should be described and illustrated.

CoOOH und CoOOD wurden definiert hydrothermal synthetisiert, chemischanalytisch und rontgenographisch charakterisiert sowie thermoanalytisch untersucht.

Anthraconaiasp. occurs in the thin nonmarine interval that lies between the Upper Millersburg Coal Member and the Lower Millersburg Coal Member (Pennsylvanian, Desmoinesian) in Warrick County, Indiana. Specimens ofAnthraconaiasp. resembleAnthraconaiathat occur in Pennsylvanian and Permian rocks of the Appalachian Basin, but they differ slightly in size, form ratios, or both. Specimens were found in massive, nonfissile gray mudstone; buff-colored, laminated limestone (ostracodal biomicrite, wackestone); and platy black shale. The only statistically significant variation between shells from these different lithologies is that shells recovered from the limestone tend to be more ovate than shells from the other two lithologies. This contradicts the findings of previous investigations in which more ovateAnthraconaiawere found in the more organic-rich sediments of a given stratigraphic sequence. This difference is probably caused by the lack of discernible change in energy level through the depositional history of the interval and suggests that changing energy levels may be more important to the control of the morphology ofAnthraconaiathan the level of organic carbon in the sediment.

The decomposition mechanism of natural and artificial hydrargillites was investigated by means of quasi-isothermal-quasi-isobaric thermogravimetry and X-ray examination. It was shown that the decomposition of artificial hydrargillites consists of three partial reactions α-Al(OH) 3 → α-AlOOH + H 2 O (1) 2 α-Al(OH) 3 ⇆ χAl 2 O 3 + 3 H 2 O (2) 2 α-AlOOH ⇆ γ-Al 2 O 3 +H 2 O (3) Each of these partial reactions is divided into further partial processes, some of which take place in a quasi-isothermal, and some in a non-isothermal way, and part of them leads to equilibrium whereas the other part does not. It was also shown that the decomposition of natural hydrargillites only takes place in the borderline case according to eqn. (2) and no boehmite is formed. However, between the two borderline cases the transition regarding the decomposition mechanism is continuous.

Die Zersetzung von AlCl3 · 6 H2O wurde im Gebiet 400 bis 1000° mittels Differentialthermoanalyse und Thermogravimetrie in Kombination mit Methoden der Gasanalyse (Massenspektrometrie und Thermogastitrimetrie) untersucht. Wahrend der Zersetzung im nichtisothermen Reaktionsschritt von 200 bis 780° kommt es zu einer relativen Cl−-Stabilisierung im Cl−- und OH−-haltigen amorphen Abbauprodukt. Dieses bildet bei 780° sprunghaft in einem Gitterordnungsprozesγ-Al2O3. Mit diesem Vorgang ist eine Masseabgabe verbunden, die auf der Abspaltung von HCl und AlCl3 beruht. H2O und HC1 aus der Gasphase senken die Aktivierungsenergie des Gitterordnungsprozesses und verschieben diesen nach niedrigeren Temperaturen.

Die Zersetzung des Aluminiumchloridhexahydrats wurde mit Differentialthermoanalyse und Thermogravimetrie in Kombination mit Thermogastitrimetrie unter Anwendung eines Q-Derivatographs untersucht. Es wurde gefunden, das die Reaktion zu Aluminiumoxid uber die Zwischenstufe eines basischen Aluminiumchlorids ablauft. Aus dem Vergleich der unter dynamischen und quasiisothermen Heizbedingungen erhaltenen Ergebnisse folgt, das diese Zwischenstufe nur unter quasiisothermen Bedingungen beobachtbar ist.

Vergleichende thermoanalytische Untersuchungen der thermischen Zersetzung von MgCl2 · 6 H2O bis 400° C bei p=1 bar unter quasiisothermen und temperaturdynamischen Bedingungen bei simultaner Gasanalyse (EGA) und Variation des H2O- und HCl-Partialdrucks uber der Substanz. Die H2O- und HCl-Abspaltung erfolgt in Stufen, deren Temperatur vom H2O-HCl-Partialdruck beeinflust wird. In Abhangigkeit von den Bedingungen ist die Uberfuhrung in MgCl2 · 4 H2O direkt aus dem Feststoff oder aus einer Schmelze in einem nichtisothermen Schritt moglich. Die Zersetzung von MgCl2 · 4 H2O vollzieht sich unter quasiisobaren Verhaltnissen in weiteren drei isothermen Reaktionen uber MgCl2 · 2 H2O und thermisch stabile basische Magnesiumchloride.

The high-strength, nickel-base alloy X-750 is susceptible to stress-corrosion cracking (SCC) in high-purity, deaerated water. Crack initiation occurs at high temperatures [>400°F (204 °C)]. Crack propagation occurs in both high-temperature and low-temperature [

Die Bildung von Kobalt(III)-hydroxid aus Co2+-haltigen Losungen mittels NaClO2 ist thermodynamisch bei pH > 1,8 moglich, wenn die Bildungsgeschwindigkeit von Kobalt(III)-hydroxid gegenuber der Zersetzungsgeschwindigkeit von NaClO2 in ClO, ClO und Cl− sehr gros ist und Sekundarreaktionen kinetisch gehemmt sind. Bei partiellem simultanem NaClO und NaOH-Zusatz verlauft die Bildung nach der formalen Bruttogleichung entsprechend den theoretischen Ableitungen. Bei Zusatz eines NaClO2-Uberschusses treten als Zersetzungsprodukte in der Losung ClO und Cl− und in der Gasphase ClO2 auf. Die Fallprodukte weisen das Rontgeninterferenzsystem der wasserhaltigen Phase CoOOH(H2O)> 0 bis 1 auf.

Weitgehend amorphisierter Quarz und Nickelpulver wurden gemeinsam in einer Schwingmuhle aktiviert. Die Benzolhydrierung dieser NiSiO2-Tragerkontakte verlauft mit der Aktivierungszeit uber ein Maximum und kann am besten durch die Gitterstorungen (Storamplitude) des Nickels erklart werden. – Schwingmahlungen der Tragerkontakte bei steigender Temperatur fuhren zu einem Ruckgang der katalytischen Aktivitat, die wiederum mit der Ausheilung der Gitterstorungen des Nickels konform geht. Nickel powder mixed with amorphous quartz is activated in a vibration mill. The catalytic activity, measured by the hydrogenation of benzene, increases with the time of activation and reaches a maximum. The activity of these catalysts is a function of the lattice distortion.– Mechanical activation with increasing temperature decreases the catalytic activity due to the loss of the lattice distortion.

In a patient with massive ascites, bouts of fever of unknown aetiology and cachexia, duodenoscopy and laparoscopy revealed white-yellow, partly confluent, nodules and plaques on the duodenal mucosa, and the surface of the liver and the peritoneum of the upper right abdominal quadrant, leading to the diagnosis of Whipple's disease. Histological examinations of these deposits revealed an accumulation of PAS-positive macrophages (SPC cells = sickle-form particle containing cells) and lysosomal bacterial inclusions under the electron-microscope. This raises the possibility of a simple endoscopic method for diagnosing Whipple's disease.

In a patient with massive ascites, bouts of fever of unknown aetiology and cachexia, duodenoscopy and laparoscopy revealed white-yellow, partly confluent, nodules and plaques on the duodenal mucosa, and the surface of the liver and the peritoneum of the upper right abdominal quadrant, leading to the diagnosis of Whipple's disease. Histological examinations of these deposits revealed an accumulation of PAS-positive macrophages (SPC cells = sickle-form particle containing cells) and lysosomal bacterial inclusions under the electron-microscope. This raises the possibility of a simple endoscopic method for diagnosing Whipple's disease.

The electrochemical proton gradient (delta/uH+) and the rate of respiration were determined as function of the work load at conditions where isolated rat heart mitochondria utilize pyruvate and/or l-palmitoyl-carnitine as hydrogen donors. Delta/uH+ was calculated from the distribution of 86Rb+ (delta psi marker) and [14C]-dimethyloxazolidine-2,4-dione (delta pH marker) between the mitochondrial matrix space and the medium. A transition from l-palmitoylcarnitine to pyruvate utilization did not change the rate of hydrogen supply or the mitochondrial energy state.

After an acute hypobaric hypoxia the mitochondrial respiratory control index is reduced in consequence of a decreased active-state respiration. The finding is paralleled by decreased uncoupled respiration and a not significantly changed resting-state respiration. Long term hypoxic exposures show adaptive traits of this criterion of mitochondrial energy metabolism. The antihypoxic effect of piracetam may be reflected in a delayed normothermic in vitro aging of mitochondrial suspension.

An improved method for the isolation of rat brain mitochondria is described. The preparation exhibits a respiratory control index (RCI) of 6 or 7.3 in the presence of pyruvate and malate or glutamate and malate, respectively. RCI decreases to 2.5 in the presence of Mg++. When the phosphorylation of extramitochondrially added or formed ADP is suppressed by carboxyatractyloside (CAT) inhibition of the adenine nucleotide translocator, the remaining respiration amounts to 6 nmol O2/min X mg mitochondrial protein. These results and the ratio of 16 to 19 from the quotient of phosphorylating active-state respiration to CAT inhibited respiration refer to a high degree of mitochondrial coupling of respiration. Therefore the remaining respiration in the presence of Mg++ is due to a phosphokinase activity located outside the inner membrane of intact mitochondria or at nonphosphorylating mitochondrial fragments. The following activities were observed: Oligomycin sensitive ATPase, 47 mU/mg protein; hexokinase, 272 mU/mg protein; creatinphosphokinase, 116 mU/mg protein; and a surprisingly low activity of adenylatekinase, 57 mU/mg protein.

The regulation of oxidative phosphorylation by the extramitochondrial ATP/ADP ratio was investigated with pyruvate (malate) or pyruvate (malate) plus octanoate as substrates in experiments with isolated rat liver mitochondria. Steady states in the supply of non-saturating substrate concentrations and the activity of oxidative phosphorylation were adjusted by means of a perifusion technique which is based on immobilisation of mitochondria on glass filters. Michaelis-Menten parameters of the pyruvate oxidation in active state respiration were determined both in the absence and presence of octanoate. Octanoate yielded only slight Km value increase, whereas the maximal rate of pyruvate oxidation was diminished to one half. Therefore, it is concluded that the inhibitory action of octanoate on pyruvate oxidation comes close to a non-competitive mechanism. The inhibitory effect of octanoate is completely reversible. When a change in substrate supply was accomplished by substituting pyruvate (malate) plus octanoate for pyruvate (malate) under conditions of a simulated extramitochondrial energy demand, respiration was stimulated and ATP/ADP ratios generated outside mitochondria were shifted to a higher value. Two different responses of the mitochondrial respiration to the extramitochondrial ATP/ADP ratios were found as a function of the presence or absence of octanoate.

Die Nachteile bei der Verwendung von Allo- und Xenotransplantaten zur temporaren Wundabdeckung von Verbrennungen, insbesondere die Schwierigkeiten der Beschaffung und Konservierung, der starken Unvertraglichkeitsreaktionen und der hohen Kosten waren Anlas fur die Entwicklung von synthetischem Hautersatz. Nachdem in jungster Zeit uber die Verwendbarkeit von Polyurethanschaumstoff-Folien (Epigard) als gunstiges Deckmaterial berichtet wurde, stellten wir uns die Aufgabe, diesen Hautersatz bezuglich seiner Haftfahigkeit, Eindammung der Wundinfektion und Vorbereitung des Wundbettes fur die nachfolgende Autotransplantation einer klinischen und histologischen Untersuchung zu unterziehen.

In der Funktionsprufung elektrischer Herzschrittmacher ist die Elektrokardiographie das wichtigste Hilfsmittel. Selbst bei haufigen Kontrollen bereitet es jedoch oft Schwierigkeiten, aus einem Ekg-Streifen ein sicheres Bild uber die Funktionsweise des Schrittmachers oder den Herzrhythmus zu gewinnen. Es war deshalb naheliegend, zur Kontrolle der Schrittmacherpatienten die Langzeitelektrokardiographie (System Holter-Avionics) einzusetzen, die eine kontinuierliche Uberprufung des Elektrokardiogramms uber durchschnittlich 15 Stunden ermoglicht, Uber unsere ersten orientierenden Erfahrungen haben wir bereits an anderer Stelle berichtet (9). Nachdem wir nun eine grosere Untersuchungsreihe abgeschlossen haben, sind weitergehende Aussagen moglich.

Nachdem verschiedene Autoren die Verwendbarkeit fetaler Kalbshaut als gunstiges Deckmaterial bei der Behandlung schwerer Verbrennungen beschrieben haben, war es Absicht unserer Untersuchungen, die Immunreaktion auf diesen Hautersatz einer histologischen Untersuchung zu unterziehen.