Dynamics of excited state proton transfer in nitro substituted 10-hydroxybenzo[h]quinolines.

The ground state tautomerism and excited state intramolecular proton transfer (ESIPT) of 10-hydroxybenzo[h]quinoline (HBQ) and its nitro derivatives, 7-nitrobenzo[h]quinolin-10-ol (2) and 7,9-dinitrobenzo[h]quinolin-10-ol (3), have been studied in acetonitrile using steady state as well as time dependent spectroscopy and quantum-chemical calculations. In addition to the enol form absorbance in the range 360-390 nm, the absorption spectra of 2 and 3 exhibit a red shifted band at ∼450 nm. Chemometric data processing, based on individual band decomposition, allowed us to estimate the position of the ground state enol-keto tautomeric equilibrium (ΔG values of 1.03 and 0.62 kcal mol-1 respectively for 2 and 3). The fluorescence stems from the keto form even if the enol form is optically excited as proven by the shape of the excitation spectra indicating that ESIPT takes place. The Stokes shift of the substituted compounds is substantially lower compared to HBQ, which follows from the fact that the substitution occurs in the formal cyclohexa-2,4-dienone moiety and leads to a decrease of the HOMO level of the keto tautomer. The pump-probe experiments show that in the nitro substituted HBQs 2 and 3 ESIPT occurs with a time constant of 0.89 ps and 0.68 ps, respectively. In both cases a mixture of the enol and proton transfer forms is optically excited. The enol form exhibits then the ESIPT and subsequently both fractions take the same relaxation path. We propose that in 2 and 3 the ESIPT path exhibits a potential energy barrier resulting in an incoherent rate governed process while in HBQ the ESIPT proceeds as a ballistic wavepacket motion along a path without significant barriers. The theoretical calculations (M06-2X/TZVP) confirm the existence of a barrier in the ground and excited states as result of the substitution.

Solvent control of intramolecular proton transfer: is 4-hydroxy-3-(piperidin-1-ylmethyl)-1-naphthaldehyde a proton crane?

The solvent dependent excited state dynamics of 4-hydroxy-3-(piperidin-1-ylmethyl)-1-naphthaldehyde (compound 2), a candidate for a molecular switch based on intramolecular proton transfer, was investigated by ultrafast spectroscopy and quantum-chemical calculations. In acetonitrile a mixture of molecules in the enol and zwitterionic proton transfer (PT) form exists in the ground state. However, the zwitterion is the energetically favored one in the electronically excited state. Optical excitation of the enol form results in intramolecular proton transfer and formation of the PT form within 1.4 ps. In addition we observe the appearance of a long living species with a rate of 1/(330 ps) which returns to the original ground state on time scales beyond 2 ns and which is attributed to the triplet state. In toluene the enol form is the only observed ground state tautomer, but no light induced proton transfer occurs. Again the long living triplet state is formed, even with a faster rate of 1/(11 ps). In methanol hydrogen bonds between 2 and solvent molecules stabilize strongly the PT form in the ground as well as in the excited state. Also in this case no light induced intramolecular proton transfer was observed but the formation of a long living species was. However, its absorption spectrum is distinctly different from the triplet state seen in acetonitrile and methanol.

4-Hydroxy-1-naphthaldehydes: proton transfer or deprotonation.

A series of naphthaldehydes, including a Mannich base, have been investigated by UV-Vis spectroscopy, NMR and theoretical methods to explore their potential tautomerism. In the case of 4-hydroxy-1-naphthaldehyde concentration dependent deprotonation has been detected in methanol and acetonitrile. For 4-hydroxy-3-(piperidin-1-ylmethyl)-1-naphthaldehyde (a Mannich base) an intramolecular proton transfer involving the OH group and the piperidine nitrogen occurs. In acetonitrile the equilibrium is predominantly at the OH-form, whereas in methanol the proton transferred tautomer is the preferred form. In chloroform and toluene, the OH form is completely dominant. Both 4-hydroxy-1-naphthaldehyde and 4-methoxy-1-naphthaldehyde (fixed enol form) show dimerization in the investigated solvents and the crystallographic data, obtained for the latter, confirm the existence of a cyclic dimer.

[An X-ray appliance for postoperative control of osteosynthesis with locking plate in patients with distal fracture of the radius]. / Anwendung einer Röntgenvorrichtung zur postoperativen Kontrolle der distalen Radiusfraktur nach winkelstabiler Plattenosteosynthese.

PURPOSE: A possible complication in regard to osteosynthetic treatment of a lower radius fracture with a locking plate is perforation of the articular surface by screws or a malpositioned ulnar fragment. In order to create good conditions for a homogeneous, reproducible X-ray picture for post-operative imaging control, an appliance for the production of standardised X-ray views has been devised. MATERIALS AND METHODS: The X-ray device was constructed at an angle of 20 degrees to the camera. The arm was positioned on the appliance in the side beam path, in shoulder adduction as well as in the dp-beam in 90 degrees abduction of the shoulder. RESULTS: Through standardisation of the X-ray technique the appliance it is able to supply comparable and reproducible X-ray images. In practice, the representation of both the joint gap and the bolt in the resulting image could be improved. CONCLUSIONS: Better and comparable picture series can be created by standardisation of the imaging technique using this X-ray device.

Ultrafast exciton relaxation in microcrystalline pentacene films.

The exciton dynamics in microcrystalline pentacene films is investigated by transient absorption measurements with 30 fs time resolution. It is found that the emission from photoexcited Frenkel excitons decays within 70 fs due to the ultrafast formation of an excitonic species with a strongly reduced transition dipole to the ground state and an absorption dipole in the plane of the film. We propose that an excimer exciton is formed and stabilized by changes of the local crystal structure. The subsequent dynamics is dominated by diffusion controlled annihilation and trapping.

Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook.

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.

Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial.

PURPOSE: A multinational trial on pediatric Hodgkin's disease (HD) with the aim to reduce the risk of long-term toxicity of combined modality treatment by restricting dose and volume of radiation therapy (RT) while maintaining the excellent treatment results of previous German multicenter trials (DAL-HD82-90). METHODS AND MATERIALS: Patients were treated according to stage of disease (CS) and defined risk factors in three treatment groups (TG) with 2, 4, or 6 cycles of combination chemotherapy. When a complete remission (CR) had been achieved, treatment was terminated without RT independent of initial stage or tumor bulk. Patients with a partial remission (PR) of >75% tumor regression were irradiated with 20 Gy using modified involved fields; in the case of PR <75% RT dose was 30 Gy, residual masses >50 mL received 35 Gy. RESULTS: From August 1995 to July 2000 a total of 956 patients have been registered, 830 as trial patients, 39% in TG1, 27% in TG2, 34% in TG3. 827 patients were evaluable by June 2001 with a median follow-up of 38 months. Chemotherapy (CTx) resulted in CR in 22%, PR >75% in 62%, PR <75% in 12%. Event-free survival (EFS) for the entire group is 90% (SD 0.01), for TG1 94%, TG2 91%, and TG3 84%; the overall survival is 97% in Kaplan-Meier-analysis. Relapse-free survival (RFS) is superior for patients with RT after PR (93%) than for those without RT after CR (89%); the difference is significant (p = 0.01) for advanced stages, however not in TG1. Seventy-two events were observed by June 2001: 28 progressions during the initial therapy or within the first 3 months, 38 relapses, 3 second malignancies, three fatal accidents or infections; 18 patients have died. CONCLUSION: Treatment results of the GPOH-HD 95 trial are excellent thus far. The reduction of RT dose and volume in PR has not caused a significant impairment of overall and event-free survival in comparison to the previous German trials; however, failure rates are higher in advanced stages when RT is omitted after achieving a CR. It is too early to tell whether the HD 95 protocol will be successful in reducing late toxicity.

[Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years]. / Multinationale Therapiestudie für den Morbus Hodgkin bei Kindern und Jugendlichen GPOH-HD 95. Zwischenbericht nach 2 1/2 Jahren.

Based on concepts of the successful German-Austrian pediatric Hodgkin studies DAL-HD 78 until-90, a new trial was initiated addressing the question whether radiotherapy can be further reduced or can be omitted in case of complete remission after initial chemotherapy, aiming at reduction of sequelae after radiotherapy, especially radiogenic second malignancies. In respect to CHEMOTHERAPY patients are stratified into 3 therapy groups (TG) according to stage and gender: 2 courses of OPPA (girls) or OEPA (boys) in TG1 (stage IA/B, IIA), and in addition 2 (TG2: stage IEA/B, IIEA, IIB, IIIA) or 4 (TG3: stage IIEB, IIIEA/B, IIIB, IVA/B) COPP courses. Boys with stage IIIB and IIIEB receive OPPA instead of OEPA. RADIOTHERAPY is administered according to response to chemotherapy independent of stage: patients with complete remission or minimal residues do not receive irradiation; patients with more than 75% tumor regression are irradiated to involved fields at a dose of 20 Gy. Doses of 30 or 35 Gy are given to regions with tumor regression below 75% or residual bulky tumor of > 50 ml, respectively. INTERIM RESULTS: From 8/95 till 1/98 we registered 385 patients under the age of 18 years from Germany, Austria, Switzerland, Sweden and the Netherlands. Therapy has been completed in 334 patients. Three patients with solitary nodular paragranuloma were treated with surgery only. Out of 331 patients 89 (26.9%) achieved a complete remission with chemotherapy. Tumor regression of more than 75% was seen in 193 (58.3%) patients and below 75% in 39 (11.8%) patients. Tumor progression during chemotherapy occurred in 1 (0.3%) patient. Response after chemotherapy was not evaluable for 9 (2.7%) patients. Radiotherapy was omitted in 91 (27.1%) patients: in TG1 50 of 142 (34%) patients, TG2 24 of 98 (24.5%) patients and TG3 18 of 94 (19.2%) patients. Initially involved regions were irradiated at a dose of 20 Gy in 164 of 334 (49.1%) patients. Doses up to 30 Gy or 35 Gy were given to 19 (5.7%) or 57 (17.1%) patients respectively. Events (tumor progression, relapse or death) occurred in 23 of 334 patients until now. The event-free survival rate is 0.91 at 2 1/2 years for all study patients and 0.89 for patients without radiotherapy. Six relapses occurred in 91 patients without radiotherapy. No relapse occurred in TG1 (n = 49), but in 5 of 24 TG2-patients, and in 1 of 18 TG3 patients without radiotherapy. As yet, the results are not significantly inferior compared with trial DAL-HD 82. Therefore this trial aiming at omitting radiation therapy in patients with complete remission after a short lasting chemotherapy will be continued. Longer follow up is necessary for final evaluations and conclusions.

Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis.

BACKGROUND: The course of tissue changes in acute myocarditis in humans is not well understood. Diagnostic tools currently available are unsatisfactory. We tested the hypothesis that inflammation is reflected by signal changes in contrast-enhanced magnetic resonance imaging (MRI). METHODS AND RESULTS: We assessed 44 consecutive patients with symptoms of acute myocarditis. Nineteen patients met the inclusion criteria revealing ECG changes, reduced myocardial function, elevated creatine kinase, positive troponin T, serological evidence for acute viral infection, exclusion of coronary heart disease, and positive antimyosin scintigraphy. We studied these patients on days 2, 7, 14, 28, and 84 after the onset of symptoms. We obtained ECG-triggered, T1-weighted images before and after application of 0.1 mmol/kg gadolinium. We measured the global relative signal enhancement of the left ventricular myocardium related to skeletal muscle and compared it with measurements in 18 volunteers. The global relative enhancement was higher in patients on days 2 (4.8+/-0.3 [mean+/-SE] versus 2.5+/-0.2; P<.0001); 7 (4.7+/-0.5, P<.0001); 14 (4.6+/-0.5, P<.0002); and 28 (3.9+/-0.4, P=.009) but not on day 84 (3.1+/-0.3; P=NS). On day 2, the enhancement was focal, whereas at later time points, the enhancement was diffuse. In patients with evidence of ongoing disease, the values remained elevated. CONCLUSIONS: Acute myocarditis evolves from a focal to a disseminated process during the first 2 weeks after onset of symptoms. Contrast media-enhanced MRI visualizes the localization, activity, and extent of inflammation and may serve as a powerful noninvasive diagnostic tool in acute myocarditis.

[5 years quality assurance in accordance with the roentgen regulation. Benefits, costs, necessary innovations]. / 5 Jahre Qualitätssicherung nach der Röntgenverordnung. Nutzen, Kosten, notwendige Weiterentwicklungen.

Guidelines and standards supplementing the German "Röntgenverordnung" initiated a complex system of quality control in diagnostic radiology. Cost and profit are analysed for two hospitals of comparable size (Klinikum Buch and Klinikum Nürberg). The considerable expenses that must be incurred for measuring devices, equipment, working time and extra charges on the one hand, are the items that are opposed to achieving a higher image quality and dose reduction on the other. Public quality control enables to demonstrate the quality and to optimise imaging procedures in diagnostic radiology. A critical evaluation of the results of quality control suggests further developments. We should consider larger time intervals for quality tests in some cases, while focussing on techniques with high radiation exposure, e.g. computed tomography, where dose reductions are highly effective.

[Experiences with a new film-screen system in pediatric thoracic radiography]. / Erfahrungen mit einem neuen Film-Folien-System in der pädiatrischen Thoraxdiagnostik.

PURPOSE: To compare the x-ray images made by the Kodak InSight Pediatric Imaging System (InSight P) with conventional film-screen systems in pediatric chest radiography. MATERIAL AND METHODS: The comparison involved chest radiographs made using Quanta-Fast-Detail/Cronex 4 (DuPont), Trimax 16/XDA (3 M) and DuPont UVR/UVL systems. The image quality of critical structures and the physical parameters of quantum interference, contrast and resolution were assessed. The energy path of the system was assessed by preparing density curves. Test conditions were in accordance with the latest guidelines of the Bundesärztekammer (German Physician's Association). RESULTS: The mediastinal area, retrocardiac and paravertebral spaces and the peripheral vessels of the lung were all displayed more distinctly using InSight P. The reason for this seems to be a lower degree of quantum interference associated with this system. With tube voltages between 60 and 80 kV, InSight P displayed a relatively low degree of sensitivity. CONCLUSION: InSight P can be used to produce predominantly high quality chest radiographs of infants between one and five years of age. However, this system has limited sensitivity in the tube voltage range recommended by the German Physicians' Association.

[CT-guided sclerosing therapy of kidney cysts. Report of experience with 100 patients]. / CT-gezielte Nierenzystenverödung. Erfahrungsbericht über 100 Patienten.

Due to its diagnostic accuracy as well as safe and accurate puncture technique CT can be used advantageously for percutaneous sclerosing therapy of renal cysts. CT-guided sclerosing therapy with pantopaque emulsions was carried out in 100 patients on an outpatient basis with altogether 107 solitary renal cysts. There were indications in all cases. Continuous follow-up of cyst involution in 96 patients with 103 cysts pointed out a reliable sclerosing effect in 95.1% of them. Major complications were neither registered in the puncture technique nor in the late urographic examinations.

[Diagnosis and therapy of mediastinal tumors in children]. / Zur Diagnostik und Therapie von Mediastinaltumoren bei Kindern.

43 mediastinal tumours differing by genesis, operability, and localisation and handled between 1970 and 1985 are reported in this paper. They called for differentiated diagnosis and therapy. Most of them (21) were of neurogenic origin. Their survival rate (86 per cent) was much higher than that recorded from abdominal tumours, probably because of a higher percentage of benign and semi-malignant processes among them. Their absolute number was 13. While computed tomography could effectively replace invasive methods of investigation, its informative potential was limited when it came to patients in infancy. Definite diagnosis was quite often obtainable only from histological examination. Diagnosis should be made soon and thoracotomy not delayed in view of potential malignancy.

[Morphology and diagnosis of acquired bladder deformities]. / Zur Morphologie und Diagnostik erworbener Harnblasenverlagerungen.

Acquired displacements of the urinary bladder refer to intrapelvic pathological anatomy. These alterations of the bladder are predominantly detected via an initial radiologic study with intravenous urography or suprapubic pelvic ultrasonography. According to their clinical incidence displacements of the bladder can occur in: pelvic space-occupying lesions; displacements in musculo-fascial defects of supporting structures as well as in extirpation cavities of the small pelvis; extrapelvic space-occupying lesions. Herniation, prolapse and descensus of the bladder can be accurately diagnosed by correct examination via intravenous urography. The diagnostics of pelvic and extrapelvic pathogenetic causes require the complex application of all methods of diagnostic imaging, the value of which is determined by clinical diagnosis and by the choice of an appropriate therapy.

[Tumors of the renal pelvis--diagnostic possibilities using CT]. / Tumoren des Nierenbeckens--Diagnostische Möglichkeiten mit CT.

The urographic results obtained in 14 patients with tumors of the renal pelvis are compared with those of computer tomography (CT), and the diagnostic possibilities emerging from CT are described. CT is superior to urography and angiography not only in the discovery of renal pelvic tumors but also in their further differentiation. In addition, CT gives information in case if bilateral processes and lymph node metastases. Nonetheless, intravenous pyelography continues to hold the first place in the diagnosis of pathological processes of the renal pelvis. This holds both for tumor detection and suspicion and for indirect signs, namely the "mute" kidney or hydronephrosis. Angiography is less information with renal pelvic tumors, and with ultrasonic diagnostics there is no sufficient experience up to now.