Pharmacodynamics of the immunosuppressive effects of the combination of tacrolimus with mycophenolate mofetil.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Richter.
Explore the source record for details and available documents.
PURPOSE: Force effect (impact, extent of foot compartment deformation) and result (fracture pattern) for midfoot fractures in car occupants is known. An analysis of the processes in the foot was intended to improve car safety. MATERIALS AND METHODS: Eleven fresh, unfrozen, unpreserved intact human cadavers (age: 36.8 (16-61) years, gender: male, race: Caucasian) were studied 24-72 h after death. In 3 cadavers (5 feet) the experimental design was established: entire cadaver fixed on a special tray in supine position, pendulum with bar impactor hitting the foot plantar to Lisfranc's joint. A custom-made pressure sensor was inserted in the ankle (A), talonavicular (TN) and calcaneocuboid (CC) joints (resolution: 1 cm2, sampling rate: 500/s). RESULTS: Sixteen feet were measured: midfoot fractures were induced in 11 feet. The maximum pressure amounted to 1.22-2.55 MPa (2.04+/-0.412) at 0.005 0.195 s (0.067+/-0.059) after impact. The maximum pressure occurred in 8 (50%) cases in the ankle, in 7 (44%) of the TN and 1 (6%) of the CC joints. A comparison of the first 200 pressure samples after impact of all sensor fields resulted in higher forces in Chopart's joint than in the ankle (t-test: p < 0.001). These force differences were higher in cases with midfoot fractures (mixed model analysis of variance: p = 0.003). CONCLUSION: Due to considerable forces in Chopart's joint we recommend a modification of the actual crash test dummy lower extremity model with an additional load cell that detects forces in the longitudinal direction of the foot axis.
LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell.
This paper examines the effect of socio-economic status on the utilisation of screening programmes and health promotion measures, based on data of a representative health survey in North Rhine-Westphalia (Germany), with a sample of 1,920 respondents. The analysis focuses especially on the utilisation of the cancer screening programme and the 'Health Check-Up' programme, which both have a high rank in German secondary prevention strategies. During the study year and the year before 29.2 % of the relevant male and 56.5 % of the female population took part in cancer screening programmes. At the same time 29.6 % of the males and 30.1 % of the females took part in the 'Health Check-Up' programme. In respect of socio-economic differences, the data confirmed the results of former studies in which non-participation of cancer screening programmes increased with decreasing social class. The social gradient was more pronounced with women than with men. While for the 'Health Check-Up' no socio-economic differences could be found, the participation rates in health promotion measures for women varied significantly with socio-economic status. For both screening programmes generally weaker statistical associations were found if the socio-economic status index was substituted by the educational level of the respondents. The findings suggest that strategies designed to increase participation of such programmes should concentrate more on lower social status persons to prevent the development of inequalities in health.
Ortho-phenylphenol (OPP) and its sodium (SOPP) and potassium (POPP) salts are used as fungicides and disinfectants. Due to the widespread use of especially OPP and SOPP, the potential for consumer exposure and some "critical" findings the toxicological database is quite extensive and complex. In experimental animals toxicity after single oral and dermal administration of these compounds is low. For the skin and mucous membranes, OPP has to be considered as irritating, and SOPP and POPP as corrosive. A large number of chronic toxicity and reproduction studies did not show any indication of oestrogen-like or other endocrine effects of OPP in the mammalian organism. No teratogenic effects were observed after the administration of OPP or SOPP in rats, mice, and rabbits. In two-generation studies in rats, OPP did not affect reproduction. The available data do not suggest a relevant potential for immunotoxic properties. The administration of high dietary concentrations of OPP to mice up to 2 years induced hepatocellular changes indicative of adaptations to metabolic demands, zonal degeneration, focal hepatocellular necrosis, and/or pigmentation of the liver. Only in male mice of one study, using a strain prone to develop hepatocellular tumors at high spontaneous incidences, the incidence of hepatocellular adenomas was increased. The incidence of hepatocellular carcinomas was not affected by treatment. The urothel of the urinary bladder (at very high doses also of the renal pelvis and the papilla) is the main target tissue after the repeated oral exposure of rats. The changes initially consist of increased mitosis, followed by simple epithelial hyperplasia, developing to a papillary and/or nodular form, later on to papillomas and transitional carcinomas. Crystals or stones in the bladder do not play a decisive role in this cascade. SOPP is more effective than OPP in this respect. Male rats are much more sensitive than females. In mice, hamsters, guinea pigs, and dogs, urothelial lesions do not develop even at very high oral dose levels. The findings in rats explain why there is a large genotoxicity/mutagenicity data base not only for OPP and SOPP but also for their metabolites on nearly all kinds of endpoints/targets. The weight of evidence suggests that genotoxicity of OPP/SOPP or their metabolites does not play a decisive role for the carcinogenicity at the urothel. Among them are lack of DNA binding of OPP to the rat bladder epithelium, the differences between OPP and SOPP, between male and female rats, between rats and mice (despite roughly comparable toxicokinetics), as well as the fact that tumors develop only at dose levels inducing hyperplasias. In addition, the strong dependence of the incidence and severity of the nonneoplastic and neoplastic bladder changes on urinary pH values (modified by feeding of ammonium chloride or sodium hydrogen carbonate) is consistent with the hypothesis of a nongenotoxic mode of action. Finally, there is no correlation between the urinary concentration of OPP or its metabolites and the incidence of hyperplasias/tumors in the urinary bladder. Both tumorigenic effects in rats and male mice are considered to represent high-dose, sex- and/or species-specific phenomena, based on nongenotoxic mechanisms of action and therefore allow the conclusion that the conventional margin of safety approaches are appropriate when assessing the risk of applications of OPP and its salts.
Explore the source record for details and available documents.
This study has considered demands placed on protective clothes for motorcyclists together with observed benefits and limitations for absorbing loads and preventing injuries. In this study, 1933 accidents involving injured motorcyclists, collected by an in-depth investigation team at ARU-MUH, were analysed to find the detailed injury patterns comparing persons with and without protective clothes. The parameters influencing the force reduction are discussed comparing impact speed, elasticity coefficient and thickness of the materials used in special protectors. Additionally, post mortem human tests were carried out to find the effectiveness of such protector devices for load reductions in the lower leg. This study showed that loads, and the subsequent risk of fractures, can be reduced efficiently by foam-plate systems. Benefits were established for using a laminate of hard and soft materials for protection against soft tissue injuries both in the accident analysis and experimental tests.
It is shown that valence-band photoemission (PE) spectra of epitaxial hcp films of U metal may be understood within a one-step model of PE based on an itinerant description of the U 5f states. Particularly, the PE intensities of the f-derived bands are correctly reproduced for photon energies between 60 and 103 eV. It is found that a cross-section minimum of the Fermi-energy feature at h(nu) = 90-94 eV, which previously was assigned to a Fano antiresonance at the 5d-->5f excitation threshold, is mainly caused by a Cooper minimum. Analogous 5f cross-section variations in the region of the 5d-->5f resonances were obtained for UPd3 and Pu metal.
PURPOSE: The purpose of our study was to evaluate the use of the galactose microbubble-based contrast agent Levovist in color Doppler sonography of uveal melanomas. We also evaluated the use of the resistance index and pulsatility index in differentiating tumor-associated vessels from normal vessels in patients with uveal melanomas. METHODS: In this prospective study, 40 patients with uveal melanoma were examined with color Doppler sonography before and after the administration of the contrast agent Levovist. The Doppler signals were recorded from both the tumor and the orbit and were evaluated quantitatively and qualitatively. RESULTS: Tumor-associated vessels were detected without contrast enhancement in 36 of 40 patients and with contrast enhancement in 38 of 40 patients. The spectral characteristics of the Doppler signals did not change after the injection of Levovist. There were no differences-qualitative or quantitative-in Doppler signals between normal and tumor-associated vessels. CONCLUSIONS: The injection of Levovist slightly improved the detection of small vessels in uveal melanomas and the orbit but did not help to differentiate between normal vessels and tumoral vessels. The differentiation of a solid tumor from subretinal hemorrhage or effusion was improved.
The general morbidity is being influenced to a great extent by diseases of the respiratory tract. Since their incidence and prevalence have been increasing, the identification of causal factors, especially of environmental origin, is of importance, not just in view of implementing preventive control strategies. Primary irritative gaseous [like sulfur dioxide (SO2)] as well as particulate pollutants (like TSP) can be regarded as causal constituents. Using the opportunity of changing levels of ambient air pollution in East Germany since 1989, the impact of SO2 and TSP on bronchitis was investigated over the last 10 years as part of several intervention studies in a locally defined homogenous population, children. The data suggest a significant association between SO2 and the prevalence of bronchitis in children but not for TSP. Considering the findings of other studies with respect to air pollution and the epidemiology of adverse health effects (especially respiratory disease), these results would amend the hypothesis put forward in a review of the literature as TSP < ultrafine particles (SO4(2-)) = SO2. Although these data show a significant association with only SO2, this does not imply that ultrafine particles, such as SO4(2-), do not contribute to the association with the observed adverse health effects. Nevertheless, the findings suggest that TSP seems less likely to be a predictor in the association with respiratory diseases, particularly not in the presence of high SO2.
HYPOTHESIS: Analysis of the current injury situation in road users not exceeding 14 years of age involved in road traffic accidents to allow conclusions regarding future prophylaxis. METHODS: Traffic accident reports and medical records from children (< 15 years of age) were analyzed for the following parameters: Type, location and mechanism of injury, Abbreviated Injury Scale (AIS), Maximum AIS (MAIS), Injury Severity Score (ISS), Delta-v, collision speed, type and duration of treatment. RESULTS: In 12,309 traffic accidents occurring in the area of Hannover, Germany between 1985 and 1998, 7.5% (n = 2,317) of the involved persons and 10.5% (n = 1,734) of the injured road users were children and adolescents. 70% sustained MAIS 1 injuries, 28% MAIS 2-4 and 1.5% MAIS 5/6 injuries. The mean ISS was 3.38. 30.3% of the injured children were car occupants, 32.1% bicyclists, 33.3% pedestrians. 30.3% of the children were unrestrained car occupants, 42.1% used safety belts designed for adults, 36% used special devices. Half of the children in cars remained uninjured, whereas only 8% of the bicyclists and 2% of the pedestrians were not injured. Severe injuries occurred in 20% of bicyclists and pedestrians at a collision speed less than 30 km/h and in 80% at more than 50 km/h. Half of those crashes could have been avoided, if the colliding vehicle would had driven about 15 km/h slower. CONCLUSION: Children have an especially high risk of injury if they are involved in accidents as pedestrians, bicyclists and unrestrained car occupants. Besides of improvements of the inner and outer car design, the use of adjusted restraining systems and bicycle helmets is likely to prevent from severe injuries. Speed reduction is a considerable factor. According to our data, the injury severity for bicyclists and pedestrians increases progressively when the collision speed exceeds 50 km/h.
In countries with a very low or non-existent prevalence of late whiplash syndrome, accident victims do not routinely hear reports of acute whiplash injury leading to chronic symptoms or disability. They do not witness such behaviour in others, and do not thereby have any expectation of such possibilities. They do not engage in a process that encourages hypervigilance for and attention to symptoms, thus eliminating many factors that promote symptom amplification. They also do not engage in a process that engineers anxiety, frustration, and resentment (that is, battling with insurance companies and proving that your pain is real). They do not change their activity in response to what they, after all, view as a minor injury. They will not amplify pre-accident symptoms, or symptoms or amplify daily life's aches and pains. They will not attribute all these different sources of symptoms to chronic damage they believe the accident caused. There is no cultural information to encourage this chronic pain behaviour being seen in other cultures.
Magnetic resonance imaging with dedicated surface coils plays a pivotal role in differential diagnosis and staging of intraocular tumors. The purpose of this study was to establish MRI criteria for the differential diagnosis of uveal melanomas and intraocular metastases. In a prospective study 44 eyes in 36 patients with intraocular metastases and 200 patients with uveal melanomas were investigated with MRI using a 1.5-T scanner and a 5-cm surface coil. Both quantitative and qualitative evaluation of the resulting images was performed. The MR signal intensities typically expected for metastases (slightly hyperintense on non-contrast T1-weighted images and hypointense on T2-weighted images compared to the vitreous body) were seen in only 23.1%. The typical melanoma signal of either moderate or strong hyperintensity on T1-weighted images and hypointensity on T2-weighted images was seen in 69.4% of the proven melanomas. Contrast enhancement was observed in both metastases and melanomas. Morphological differences between metastases and melanomas were detected in tumor size, shape, position, frequency of retinal detachment, and homogeneity of the tumor. Differentiation between intraocular metastases and uveal melanoma is limited by overlap of signal intensities. Some improvement is achieved with morphologic criteria.
BACKGROUND AND AIMS: Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene. METHODS: We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls. RESULTS: The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations. CONCLUSIONS: The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.
Between 1985 and 1995, 9380 traffic accidents occurring in the area of Hannover, Germany, were analysed; 12428 individuals had been injured and 387 (3.1%) had sustained a pelvic-ring injury (AIS(PELVIS)>2). In 131 cases (34%), the injuries were further classified (Pennal and Tile) and a technical reconstruction made of the accident: 52% were type A, 27% type B and 21% type C injuries; 46% were in cars, 12% on motorised two-wheelers, 10% on bicycles and 1% in utility vehicles; 31% were pedestrians. Pelvic-ring injuries occurred in restrained vehicle occupants in accidents with a (delta)V of more than 30 km/h, whereas they occurred in a considerable proportion of unrestrained vehicle occupants, pedestrians and bicyclists at lower (delta)V or collision speed. The percentage of B- and C-type injuries increased in crashes with higher (delta)v or collision speed. In addition to further improvements of the passive safety, lower collision speeds or (delta)V would reduce or prevent pelvic-ring injuries. Due to the small number of occupants protected by airbags in this study, their protective effect for the pelvis could not be assessed. The reconstruction of pelvic-ring injury mechanism in traffic accidents is possible when technical and medical factors are considered.
The authors present a thirty two years old women complaining of a temporomandibular joint ankylosis. History revealed a mandibular trauma sustained during the early infancy. The patient presented a typical bird face deformity with a maximal mouth opening of zero millimiter. Facing the squelettal deformation, the authors decide to combine a simultaneous costochondral graft with bilateral horizontal branch distraction. Good functional and aesthetic results allow the patient to return to a good social integration with no sign of recurrence at the medium term follow-up.
Explore the source record for details and available documents.
Explore the source record for details and available documents.