MMF-a new cornerstone in immunosuppressive therapy after cardiac transplantation.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
M Richter
Publications and source records attributed to M Richter.
MMF significantly reduces the transendothelial migration of graft infiltrating leucocytes.
Explore the source record for details and available documents.
Journal Article↗
Do vascular compartments differ in the development of chronic rejection? AT(1) blocker candesartan versus Ace blocker enalapril in an experimental heart transplant model.
BACKGROUND: Accelerated coronary artery disease (ACAD), a serious consequence after heart transplantation, is characterized by diffuse, concentric myointimal proliferation in the arteries. Increasing evidence supports the existence of a local renin-angiotensin system and the role of angiotensin-II in smooth muscle cell proliferation. We investigated the effect of angiotensin-II blocker candesartan and angiotensin-converting enzyme (ACE) inhibitor enalapril on experimental ACAD in a rat model. METHODS: After heterotopic cardiac transplantation (Fisher to Lewis), recipients received 20 mg/kg/day candesartan or 40 mg/kg/day enalapril per os. Two groups of animals received additional pre-treatment with candesartan or enalapril 7 days before transplantation, and treatment was continued after grafting. All study groups including the controls received 3 mg/kg/day of sub-cutaneous cyclosporine for immunosuppression. A syngeneic group (Lewis to Lewis), serving as extra control, did not receive any treatment. Eighty days after grafting, we assessed the extent of ACAD in large and small arteries, using digitizing morphometry and expressed as mean vascular occlusion (MVO). RESULTS: In enalapril and candesartan pre- and post-treated animals, we observed significant reduction of MVO of intramyocardial arteries compared with the cyclosporine group (p < 0.005), to levels similar to the syngeneic transplants. MVO of epicardial arteries in enalapril and candesartan pre- or posttreated animals did not significantly differ from cyclosporine controls (p > 0.05). CONCLUSION: Our results support the hypothesis of 2 proliferative compartments in the development of ACAD, with differing receptor or enzyme distribution: the compartment of small, intramyocardial arteries in which ACAD can be reduced by ACE or AT(1) blockade, and that of large, epicardial arteries in which inhibition fails.
Angiotensin Receptor Antagonists↗
The EndoPearl device increases fixation strength and eliminates construct slippage of hamstring tendon grafts with interference screw fixation.
PURPOSE: The EndoPearl (Linvatec, Largo, FL), a biodegradable device to augment the femoral interference screw fixation of hamstring tendon grafts has been developed. The first objective of this study was to compare the initial fixation strength of quadrupled hamstring tendons and biodegradable interference screw fixation with and without the application of the EndoPearl device. The second objective was to determine the influence of the EndoPearl device on the fatigue behavior under incremental cyclic loading conditions in a simulation of critical fixation conditions. TYPE OF STUDY: Biomechanical study. METHODS: Fresh human hamstring tendons were harvested and grafts were fixed with biodegradable poly-L-lactide interference screws. Twenty proximal calf tibias were used to compare the initial fixation strength of the study and the control group. In the study group, the EndoPearl device was secured to the graft using two No. 5 Ethibond sutures (Ethicon, Somerville, NJ). Specimens were loaded until failure in a materials testing machine. For cyclic testing, human hamstring tendons and 20 distal porcine femurs were used. Critical graft fixation conditions were simulated by increasing tunnel diameter 2 mm over the graft diameter. Grafts were loaded progressively in increments of 100 N until failure; 100 cycles were applied per load increment. RESULTS: Graft fixation with the additional EndoPearl device had a significantly higher maximum load to failure (658.9 +/- 118.1 N v 385.9 +/- 185.6 N, P =.003) and stiffness (41.7 +/- 11 N/mm v 25.7 +/- 8.5 N/mm). Graft fixation with the EndoPearl device sustained a significant higher total number of cycles (388.5 +/- 125.6) compared with the control group (152.8 +/- 144.9, P =.002). CONCLUSIONS: We demonstrated that the augmentation of a hamstring tendon graft with the EndoPearl device increases interference screw fixation strength significantly. Under dynamic loading conditions, specimens of the study group sustained substantially higher loads and a larger number of cycles, which indicates a greater resistance to graft slippage. The application of the EndoPearl device may also allow for a secure soft-tissue graft fixation with interference screws in cases of critical fixation conditions.
Absorbable Implants↗
[Does Epping resection arthroplasty lead to loss of hand strength? A prospective study].
FCR-sling resectional arthroplasty does not definitely prevent a proximalisation of the first metacarpal bone. Since power transmission of the thenar muscles requires a particular length of the thumb, does proximalisation lead to a reduction of grip strength of the hand? In a prospective study, hand-, key- and pinch-grip strength was compared to preoperative data. Pain intensity and thumb mobility were also examined. In comparison to preoperative data, the pain-free pinch grip improved 60% after three months and 100% after 12 months (p < 0.01). The maximum pinch grip improved 11% after three and 34% after 12 months (p < 0.01). The pain-free key grip improved 22% after three months and 50% after 12 months (p < 0.01). The maximum key grip showed a fair reduction after three months, but after 12 months the key pinch strength came up to preoperative level. The hand grip strength showed a statistically significant improvement of 9% after three months and 34% after 12 months (p < 0.01). After one year, 80% of the patients were completely painfree. There was no clinically relevant disturbance of thumb movement following surgery. Owing to proximalisation of the first metacarpal, a scapho-metacarpal distance of 5.3 (2-9) mm was measured. Despite proximalisation of the first metacarpal, a significant improvement of the grip strength was observed, which was rooted in simultaneous pain reduction.
Aged↗
Enhanced in vivo IgE production and T cell polarization toward the type 2 phenotype in association with indoor exposure to VOC: results of the LARS study.
The association between indoor exposure to volatile organic compounds (VOC), prevalence of allergic sensitization and cytokine secretion profile of peripheral T cells was studied in 3 year old children of the LARS study (Leipzig Allergy Risk Children Study) to investigate the role of VOC exposure as a risk factor for the development of atopic disease. Indoor VOC exposure was measured over a period of 4 weeks in infants' bedrooms using a passive sampling system. Specific IgE antibodies to food, indoor and outdoor allergens were measured by the Pharmacia CAP system and correlated to VOC exposure (n = 120). In addition, cytokine producing peripheral T cells (interleukin(IL)-4, interferon(IFN)-gamma) were measured in a subgroup of 28 children by means of intracellular cytokine staining. For the first time we were able to show that exposure to alkanes (C6, C9, C10) and aromatic compounds (toluene, o-xylene, m + p-xylene, 2-, 3- and 4-ethyl-toluene, chlorobenzene) may contribute to the risk of allergic sensitization to the food allergens milk and egg white (Odds ratios between 5.7 and 11.2). Moreover, significantly reduced numbers of CD3+/CD8+ peripheral T cells were found in children exposed to alkanes (C9-C13), naphthalene and chlorobenzene. Exposure to benzene, ethylbenzene and chlorobenzene was associated with higher percentages of IL-4 producing CD3+ T cells. Both an increase in IL-4 producing type 2 T cells and a reduction of IFN-gamma producing type 1 T cells may contribute to a type 2 skewed memory in response to allergens. Therefore, we suggest exposure to VOCs in association with allergic sensitization to be mediated by a T cell polarization toward the type 2 phenotype.
Air Pollution, Indoor↗
The [15N]methacetin liver function test characterizes multicomponent exposure of children in industrially polluted regions.
The [15N]methacetin urine test for assessing disturbances of the cytochrome P450-aided oxygenation of xenobiotics in the human liver has been approved in several environmental health studies. A recent longitudinal study of kindergarten children near chemical and mining companies undergoing fundamental restructuring showed high, seasonally fluctuating SO2 burden which was well correlated with alterations in the mean liver states of the children. At one point the correlation disappeared, together with indications of large amounts of chlorinated compounds overflowing locally at nighttime. This was finally proven by analyzing urine samples from the children for trichloroacetic acid (TCA). Chlorinated ethanes and ethenes-the precursors of TCA-seemed to dominate the air pollution and to affect the hepatic detoxification capacity. We concluded that the methacetin liver function test reflects multicomponent exposure, including acute monopolization by a dominant pollutant for a time.
Acetamides↗
Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal carcinogenesis and prevent or revert the growth of premalignant colonic polyps. They inhibit cyclooxygenase (COX) but recent data indicate that this is not the only or even the most important mechanism of inhibition in colorectal tumor cells. We have used colonic carcinoma and adenoma cell lines to study the effects of the NSAID sulindac sulfide, its COX-inactive metabolite, sulindac sulfone, and the isoenzyme-specific inhibitors SC58125, SC236 and SC58560 on tumor cell growth in relation to COX-2 expression and prostaglandin production. To establish the role of COX-2 in NSAID action, we constructed clones expressing different levels of COX-2 from SW480 cells. All five compounds inhibited DNA synthesis and/or induced apoptosis, each with a characteristic pattern. ID(50)s were very similar in all the cell lines and were independent of COX expression, except for the COX-1 inhibitor SC58560, which was least effective in HT29/HI1, the cell line expressing the highest level of COX-1 (ID(50) 70 microM; in other cells lines the ID(50) was 15 microM). For all other compounds ID(50) concentrations varied less than two-fold: 25-40, 40-90 and 150 microM for SC236, sulindac sulfide and sulindac sulfone, respectively. SC58125 was the weakest inhibitor, never causing >50% cell loss. All compounds modulated expression of Bcl-2 and Bak and activated caspase 3. Overexpression of COX-2 in SW480 cells protected them against induction of apoptosis by sulindac sulfide. The effect was restricted to clones producing high levels of prostaglandin E(2). In summary, our data indicate that both COX-dependent and COX-independent mechanisms are involved in NSAID-induced growth in colorectal tumor cells. The concentrations necessary to inhibit growth were higher than serum concentrations that can be obtained in vivo, indicating that the therapeutic effect of NSAIDs cannot be explained by a direct effect of NSAIDs on the epithelial cells alone. For therapeutic purposes, compounds using different targets could be used to minimize side effects while optimizing therapeutic effect.
Adenoma↗
Foot fractures in restrained front seat car occupants: a long-term study over twenty-three years.
OBJECTIVES: To analyze the mechanism of injury for foot and ankle fractures resulting from automobile accidents to create a basis for developing an improved design for protection. DESIGN: Retrospective. SETTING: Level I trauma center with accident research unit. PATIENTS: Automobile accident reports and medical records of individuals injured in the accidents. MAIN OUTCOME MEASUREMENTS: Technical indicators (collision type, impulse angle, deltav, and extent of vehicle deformation) and clinical data (injury location and severity [abbreviated injury scale and injury severity score] and long-term outcome). RESULTS: From 1973 to 1996, 15,559 car accidents were analyzed. Two hundred sixty-one front seat occupants sustained fractures of the foot and ankle (ankle, 41 percent; forefoot, 29 percent; midfoot, 20 percent; and hindfoot, 10 percent). Seventy-five percent of the fractures were classified abbreviated injury scale(foot) 2. The incidence, location, and abbreviated injury scale(foot) category of fractures were similar between driver (n = 210) and front seat passenger (n = 51). Fifty percent of the fractures occurred in head-on collisions and 34 percent occurred in accidents with multiple collisions. The deltav ranged in 82 percent of car crashes between fifteen and sixty kilometers per hour. The deltav and extent of foot compartment deformation correlated with the abbreviated injury scale. During our investigation, deltav increased; the injury severity score decreased; and the extent of deformation did not differ significantly. CONCLUSIONS: Although overall car passenger safety has improved, the relative incidence of foot and ankle fractures has increased. Comparing drivers and front seat passengers, the foot pedals, steering wheel, or the asymmetric design of the dashboard did not influence injury incidence, mechanism, or severity. Foot fractures are mainly caused by the foot compartment deformation in head-on collisions, and therefore improvements in foot compartments are essential for fracture prevention.
Abbreviated Injury Scale↗
Correlation between crash severity, injury severity, and clinical course in car occupants with thoracic trauma: a technical and medical study.
BACKGROUND: The crash mechanisms and clinical course of car occupants with thoracic injury were analyzed to determine prognostic factors and to create a basis for injury prophylaxis. METHODS: A technical and medical investigation of car occupants with a thoracic injury (Abbreviated Injury Scale-thorax [AIS(THORAX)] > or = 1) at the scene of the crash and the primary admitting hospital was performed. RESULTS: Between 1985 and 1998, 581 car occupants sustained a thoracic injury. Mean parameter values were as follows: AIS(THORAX), 2.5; Hannover Polytrauma Score (PTS), 21.4; Injury Severity Score (ISS), 24.2; Delta-v, 49.6 km/h (30.8 mph); and extent of passenger compartment deformation (DEF) (scale, 1--9), 4.0. In 19% (n = 112) of patients involved, the clinical course was evaluated: AIS(THORAX), 2.5; PTS, 20.0; ISS, 19.3; Delta-v, 50.1 km/h (31.1 mph); DEF, 3.9; intensive care unit time, 8.3 days; ventilation time, 5.7 days; and hospital stay, 15.3 days. In the groups with higher AIS(THORAX), ISS, PTS, and intensive care unit and ventilation time, higher Delta-v and DEF occurred. In patients with longer hospital stay, higher Delta-v, but no difference in DEF occurred. CONCLUSION: The injury severity and the clinical course demonstrated a positive correlation with the crash severity. Therefore, our technical accident analysis allows prediction of the severity of injury and the clinical course. It may consequently serve as a tool for development of more sophisticated injury prevention strategies and may improve passive car safety.
Abbreviated Injury Scale↗
Head injury mechanisms in helmet-protected motorcyclists: prospective multicenter study.
BACKGROUND: In a prospective study, three research groups at Hannover (H) and Munich (M) in Germany and Glasgow (G) in the United Kingdom collected data from motorcycle crashes between July 1996 and July 1998 to investigate head injury mechanisms in helmet-protected motorcyclists. METHODS: The head lesions of motorcyclists with Abbreviated Injury Score-Head (AISHead) 2+ injuries and/or helmet impact were classified into direct force effect (DFE) and indirect force effect (IFE) lesions. The effecting forces and the force consequences were analyzed in detail. RESULTS: Two-hundred twenty-six motorcyclists (H, n = 115; M, n = 56; and G, n = 55) were included. Collision opponents were cars (57.8%), trucks (8.0%), pedestrians (2.3%), bicycles (1.4%), two-wheel motor vehicles (0.8%), and others (4.2%). In 25.4% no other moving object was involved. The mean impact speed was 55 km/h (range, 0-120 km/h) and correlated with AISHead. Seventy-six (33%) motorcyclists had no head injury, 21% (n = 48) AISHead 1, and 46% (n = 103) AISHead 2+. Four hundred nine head lesions were further classified: 36.9% DFE and 63.1% IFE. Lesions included 20.5% bone, 51.3% brain, and 28.1% skin. The most frequent brain lesions were subdural hematomas (22.4%, n = 47) and subarachnoid hematomas (25.2%, n = 53). Lesions of skin or bone were mainly DFE lesions, whereas brain lesions were mostly IFE lesions. CONCLUSION: A modification of the design of the helmet shell may have a preventative effect on DFE lesions, which are caused by a high amount of direct force transfer. Acceleration or deceleration forces induce IFE lesions, particularly rotation, which is an important and underestimated factor. The reduction of the effecting forces and the kinetic consequences should be a goal for future motorcycle helmet generations.
Accidents, Traffic↗
Fractures and fracture dislocations of the midfoot: occurrence, causes and long-term results.
Etiology and outcome of 155 patients with midfoot fractures between 1972 and 1997 were analyzed to create a basis for treatment optimization. Cause of injuries were traffic accidents (72.2%), falls (11.6%), blunt injuries (7.7%) and others (5.8%). Isolated midfoot fractures (I) were found in 55 (35.5%) cases, Lisfranc fracture dislocations (L) in 49 (31.2%), Chopart-Lisfranc fracture dislocations (CL) in 26 (16.8%) and Chopart fracture dislocations (C) in 25 (16%). One hundred and forty eight (95%) of the midfoot fractures were treated operatively; 30 with closed reduction, 115 with open reduction, 3 patients had a primary amputation. Seven (5%) patients were treated non-operatively. Ninety seven (63%) patients had follow-up at an average of 9 (1.3-25, median 8.5) years. The average scores of the entire follow-up group were as follows: AOFAS - sum of all four sections (AOFAS-ET): 296, AOFAS-Midfoot (AOFAS-M): 71, Hannover Scoring System (HSS): 65, and Hannover Questionnaire (Q): 63. Regarding age, gender, cause, time from injury to treatment and method of treatment no score differences were noted (t-test: p>0.05). L, C or I showed similar scores and CL significantly lower scores (AOFAS-ET, AOFAS-M, HSS, Q). The highest scores in all groups were achieved in those fractures treated with early open reduction and operative fixation. Midfoot fractures, particularly fracture dislocation injuries, effect the function of the entire foot in the long-term outcome. But even in these complex injuries, an early anatomic (open) reduction and stable (internal) fixation can minimize the percentage of long-term impairment.
Adolescent↗
Helicobacter pylori prevalences and risk factors among school beginners in a German urban center and its rural county.
In 1998, the Helicobacter pylori [(13)C]urea breath test was offered to all school beginners (birth cohort 1991/1992) in the city of Leipzig and in Leipzig County, Germany, to determine the colonization prevalence and potential transmission pathways of the bacterium. A total of 3,347 school beginners participated in the test, and 2,888 parents completed the detailed, self-administered questionnaire. The H. pylori prevalence was 6.5% [95% confidence interval (CI), 5.3-7.6] in the city and 5.7% (CI, 4.2-7.0) in the county. Using cluster analysis (WARD's method, Euclidean distances), we identified different sets of variables (confirmed by multivariate logistic regression analyses [odds ratios (ORs)] that are signficantly associated with H. pylori positivity. Among city children, the risk is significantly increased with contact to a pet hamster (OR = 2.4; 95% CI, 1.2-4.7; p < 0.015) and travels to Asian countries (OR = 3.7; 95% CI, 1.6-8.7; p < 0.002). Among county children, H. pylori positivity increased significantly with drinking of water from nonmunicipal sources (OR = 16.4; 95% CI, 3.1-88.5; p < 0.001), more than 3 children living in a household (OR = 4.2; 95% CI, 1.2-14.6; p < 0.02), and contact with pet hamsters (OR = 2.4; 95% CI, 1.0-5.7; p < 0.04). These data suggest that, in a general population sample, indirect fecal-oral transmission and living conditions are important risk factors in the spread of H. pylori infection. However, clinical symptoms do not necessarily indicate H. pylori positivity.
Breath Tests↗
No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism (CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients.
BACKGROUND: A substantial proportion of the variability in the absorption and clearance of cyclosporin A (CsA) after oral administration has been attributed to variability in liver cytochrome P-450 3A4 (CYP3A4) activity and intestinal P-glycoprotein (P-gp) concentration. A polymorphism in the CYP3A4 promoter region, termed "variant" allele CYP3A4-V, was postulated to be associated with altered CYP3A4 enzyme activity. A polymorphism in exon 26 (C3435T) of the multidrug resistance-1 (MDR-1) gene was correlated with intestinal expression and in vivo activity of P-gp. METHODS: We investigated the occurrence of both polymorphisms in 124 stable Caucasian renal transplant recipients (>6 months after transplantation) on CsA as the primary immunosuppressant. Real-time, rapid-cycle PCR methods were developed and used for genotyping. RESULTS: The estimated allele frequencies for the MDR-1 C3435T allele (54%) and the CYP3A4-V allele (4.8%) were similar to those reported for Caucasian populations. No significant differences were found for the CsA doses needed to maintain similar CsA trough concentrations in patients with and without the CYP3A4-V allele or in patients with different MDR-1 C3435T genotypes. Furthermore, neither of the polymorphisms investigated was associated with renal function as assessed by creatinine plasma concentration or, in a retrospective analysis, the incidence of acute rejection. CONCLUSIONS: These findings suggest that the MDR-1 C3435T mutation and the CYP3A4-V variant are not major determinants of CsA efficacy in renal transplant recipients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Cooper minima in the photoemission spectra of solids.
Variations of the photoionization cross section of valence states as a function of interatomic distance are studied by means of atomic and solid-state density functional approaches and compared with photoemission data. In contrast to the free atom case, a series of Cooper minima is found for 4d, 5d, and 5f states in Pd, Ag, Au, and U metals. The discovered fundamental phenomenon is of high importance for the correct interpretation of photoemission data.
Journal Article↗
Incorporation of gallium into zeolites: syntheses, properties and catalytic application.
Explore the source record for details and available documents.
Journal Article↗
Magnetic splitting of valence states in ferromagnetic and antiferromagnetic lanthanide metals
The magnetic splitting of Delta(2) valence states in the heavy lanthanide metals Gd, Tb, Dy, and Ho was studied in epitaxial films by angle-resolved photoemission, revealing an essentially Stoner-like temperature dependence in all cases. It scales linearly with the 4f spin moment, even in the case of the helical antiferromagnet Ho. Such a behavior can be explained by a substantial localization of the corresponding wave function in the c direction. The helical magnetic structure was confirmed for the thin Ho films by in situ resonant magnetic x-ray diffraction.
Journal Article↗
Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo.
Adeno-associated virus (AAV) vectors might offer solutions for restenosis and angiogenesis by transducing nondividing cells and providing long-term gene expression. We investigated the feasibility of vascular cell transduction by AAV vectors in an in vivo rabbit carotid artery model. Time course of gene expression, inflammatory reaction to the vector, and effects of varying viral titer, exposure time, and intraluminal pressures on gene expression were examined. Recombinant AAV vectors with an Rous sarcoma virus promoter and alkaline phosphatase reporter gene were injected intraluminally into transiently isolated carotid segments. Following transduction, gene expression increased significantly over 14 days and then remained stable to 28 days, the last time point examined. Medial vascular smooth muscle cells were the main cell type transduced even with an intact endothelial layer. Increasing the viral titer and intraluminal pressure both enhanced transduction efficiency to achieve a mean of 34 +/- 7% of the subintimal layer of smooth muscle cells expressing gene product. A mild inflammatory reaction, composed of T cells with only rare macrophages, with minimal intimal thickening was demonstrated in 40% of transduced vessels; inflammatory cells were not detected in sham-operated control arteries. These findings demonstrate that AAV is a promising vector for intravascular applications in coronary and peripheral vascular diseases.
Alkaline Phosphatase↗