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T Meyer

Publications and source records attributed to T Meyer.

At least 73 records · Page 4Linked to original sources
PubMed2003

Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures.

Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.

Aminoquinolines↗
PubMed2003

Cutaneous precancers in organ transplant recipients: an old enemy in a new surrounding.

Premalignant and malignant epithelial lesions are acknowledged as being the most frequent neoplasia in long-term immunosuppressed patients such as organ-transplant recipients. Paralleling the constant improvement in modern transplant techniques, their incidence increases together with the growing survival time post-transplantation, reaching 40% to 60% after 20 years. Against the background of lifelong immunosuppression, the impact of accepted cancer inducers and promoters such as ultraviolet radiation, oncogenic viruses and individual susceptibility has to be closely scrutinized. Precancerous lesions such as actinic keratoses in transplant patients progress more rapidly into squamous cell carcinomas, showing an increased tendency to metastasize. As it remains impossible to identify and consequently treat those lesions that may progress into invasive carcinoma, the best prophylaxis for nonmelanoma skin cancer in organ-transplant recipients may be the treatment of all existing precancerous lesions. As reduction of the immunosuppressive therapy is rarely practicable, other terms of prophylaxis and treatment, such as immune response modifiers, have to be considered.

Adjuvants, Immunologic↗
PubMed2003

[Difficulties in controlled inhalation of alpha 1-protease inhibitor].

In this paper a number of studies will be summarized which were designed to improve the inhalation of alpha 1 -protease inhibitor in patients with alpha 1-protease inhibitor deficiency. A pilot study has shown that the high inter-individual variability of drug deposition in the lungs is due to heterogeneous breathing patterns of the patients. Controlling the breathing pattern led to a significantly decreased variability. Then it was studied which particle size and breathing pattern resulted in highest peripheral lung deposition in patients with emphysema. It was found that for 3 - 4 microm particles and slow inhalation flow rate the peripheral deposition increases with increasing inhalation volume. After the development of an inhalation device which allows to perform controlled inhalations in clinical practice it was shown that this device, in combination with a breathing pattern individually normalized to the patients lung function, allows to deposit nearly 60 % of the drug into the patients lung periphery.

Administration, Inhalation↗
PubMed2003

[Historical development of the surgical treatment of the undescended testicle].

An undescended testicle can be found in about 3-4% of all newborns and in 21-23% of all premature infants. In most of the young patients, the testicle will descend spontaneously during the first year of life. Thus, at the end of the second year of life, an undescended position of the testis will remain in 1-2% of all children. Since the first successful surgical treatment of the undescended testicle by Max Schüller 120 years ago in Munich, many various surgical procedures have been described. This paper gives an overview starting with the historical development of the operative treatment of the undescended testicle and leading up to the modern techniques used today.

Age Factors↗
PubMed2003

[Changes and complication rate in surgery for thoracic esophageal carcinoma].

AIM: In an analysis over 22 years it was investigated which parameters have changed in the operative treatment of thoracic esophageal carcinoma over time and in how far they have influenced complication rate. PATIENTS AND METHODS: Between 1978 and 1999 386 patients (350 men, 36 women) underwent resection for thoracic esophageal carcinoma (squamous cell carcinoma n=300, adenocarcinoma n=86). Cervical tumors were excluded from analysis. The time periods from 1978 to 1988 (n=242) and from 1989 to 1999 (n=144) were separately analyzed and compared with respect to age, sex, histological type, main tumor location, neoadjuvant therapy, method of operation, esophageal substitute and positioning of the substitute, R-status, pT/pN classification, UICC stage, number of dissected lymph nodes, complication rate, postoperative mortality and survival. RESULTS: Comparison of the two time periods showed a significant increase in adenocarcinomas and main tumor location in the lower thoracic third of the esophagus. Furthermore, significant changes concerning the indication of neoadjuvant chemoradiation, operative approach, esophageal substitute, R-status and number of dissected lymph nodes were observed. Tumor stage (pT/pN classification and UICC stage) significantly shifted towards earlier stages. Total complication rate dropped tendentially form 68.5 % to 59.0 % (p=0.061). Hospital mortality was significantly reduced from 24 % to 12.5 %, whereas anastomotic leakages and multiorgan failure remained on a constant level. Median survival of R0 resected patients was significantly prolonged from 19 months to 34 months. CONCLUSIONS: The increase of esophageal adenocarcinoma, a more strict patient selection (staging, functional status), standardization of operative technique as well as an optimized intensive care management are among the important changes in the operative management of thoracic esophageal carcinoma that have resulted in an improvement of prognosis of curatively resected patients. In spite of a more aggressive operative approach, i. e. lymph node dissection, operative mortality could be reduced by nearly 50 % in the face of a tendentially declining total complication rate.

Adenocarcinoma↗
PubMed2003

[Controlled inhalation of beta2-sympaticomimetica after bronchial provocation].

The results of several studies indicate that controlling the breathing pattern (inhaled volume and flow rate) during inhalation increases the efficacy of drug delivery to the lungs. By inhaling slowly, deeply and under controlled conditions, intrapulmonary deposition of aerosol and its reproducibility can be increased. However, it has not yet been proven that such inhalations are well tolerated by patients, especially those with airway obstructions. In this study 12 patients with mild asthma underwent a bronchial provocation test. The following broncholysis was performed with controlled, slow, and deep inhalation using the AKITA-device. The patients were asked about the convenience of this inhalation using a questionnaire. In 80 % the controlled inhalation was judged as convenient, neither as too slow nor as too fast, neither as too deep nor as too shallow. Thus it turned out that controlled deep and slow inhalations are convenient even for patients with mild airway obstruction.

Administration, Inhalation↗
PubMed2003

Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices.

Patients with hereditary alpha1-proteinase inhibitor (alpha1-PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, alpha1-PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled alpha1-PI (Prolastin) was studied using four different commercial inhalation devices (PARI-LC Star, HaloLite, and AKITA system in combination with LC Star and Sidestream) in six patients with alpha1-PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled alpha1-PI. This time was shortest for the AKITA system (18-24 min) and significantly higher for the PARI-LC Star (44 min) and the HaloLite (100 min). The higher efficiency of drug delivery using the AKITA system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.

Administration, Inhalation↗
PubMed2002

Metabolic profile of 4 h cycling in the field with varying amounts of carbohydrate supply.

Several laboratory studies have demonstrated a performance-enhancing effect of carbohydrate (CHO) supplementations during endurance sessions of long duration. However, the transferability of these results to real training and competition circumstances has not been conclusively shown. Therefore, we tried to test the influence of graded CHO substitution on substrate utilization and selected physiological parameters under standardized but practically orientated field conditions. Fourteen endurance-trained male subjects [mean (SD): 25 (5) years, 72 (9) kg, .VO(2max) 67 (6) ml.min(-1).kg(-1), individual anaerobic threshold (IAT) 269 (30) W] after a stepwise increasing pre-test had to perform three 4-h endurance rides on their own bicycles with simultaneous spiroergometry: constant workload 70% IAT (monitoring by SRM-System). Before and during exercise, solutions without (0%), with 6% or 12% CHO were administered double-blindly and in randomized order (total volume: 50 ml.kg(-1)). After cessation of exercise, significant differences between 0% and both CHO concentrations were detected for blood glucose (GLU; 75 mg dl(-1) for 0% vs 101 mg dl(-1) for 6% vs 115 mg dl(-1) for 12%; P<0.001) and respiratory exchange ratio (0.84 vs 0.88 vs 0.90; P<0.01; correlation to GLU: r=0.46, P<0.05). Free fatty acids (0.19 vs 0.16 vs 0.10 mmol l(-1)) and glycerol (0.41 vs 0.22 vs 0.12 mmol l(-1)) were significantly different between the endurance trials in a dose-dependent manner (both P<0.001). Lactate concentration ( P=0.42) and heart rate ( P=0.12) had no significant influence from CHO substitution. We conclude that CHO substitution during 4-h endurance training inhibits lipolysis in a dose-dependent manner and enhances aerobic glycolysis. This proves that earlier laboratory findings can be replicated under field conditions using modern portable equipment.

Adult↗
PubMed2002

Maximal oxygen uptake during field running does not exceed that measured during treadmill exercise.

Modern ergometric equipment enables the simulation of laboratory maximal oxygen uptake (.VO(2max)) testing in the field. Therefore, it was investigated whether the improved event specificity on the track might lead to higher .VO(2max) measurements in running. Identical protocols were used on the treadmill and on the track (speed was indicated by a computer-driven flashing light system). Ambulatory measurements of gas exchange were carried out throughout both tests, which were executed in randomized order. There were no significant differences ( P=0.71) in .VO(2max) between treadmill [4.65 (0.51) ml.min(-1)] and field tests [4.63 (0.55) ml.min(-1)]. However, the test duration differed significantly ( P<0.001) by approximately 5%: treadmill 691 (39) s; field test 727 (42) s. With the exception of maximum heart rate (HR(max); significantly higher in the field with P=0.02) all criteria for the degree of effort were similar between the two tests. However, the difference in HR(max) at less than 2 beats.min(-1), was practically negligible. Submaximal measurements of oxygen uptake and minute ventilation were significantly higher on the treadmill ( P<0.001 for both parameters). In summary, field tests with incremental running protocols do not result in higher .VO(2max) measurements compared to laboratory treadmill exercise. A better running economy on the track results in higher maximal velocities and longer exercise durations being sustained. The determination of .VO(2max) is not a reasonable application for ambulatory gas exchange measurements because laboratory values are not surpassed.

Adult↗
PubMed2002

Finite size scaling in the two-dimensional XY model and generalized universality.

In recent works [S. T. Bramwell, P. C. W. Holdsworth, and J.-F. Pinton, Nature (London) 396, 552 (1998); S. T. Bramwell et al., Phys. Rev. Lett. 84, 3744 (2000)], a generalized universality has been proposed, linking phenomena as dissimilar as two-dimensional (2D) magnetism and turbulence. To test these ideas, we performed Monte Carlo simulations of the 2D XY model. We found that the shape of the probability distribution function for the magnetization M is non-Gaussian and independent of the system size-in the range of the lattice sizes studied-below the Kosterlitz-Thoules temperature. However, our results suggest that in the full 2D XY model the shape of these distributions has a slight dependence on temperature-for finite volume-below the lattice-shifted critical temperature T*(L). This behavior can be explained by using renormalization group arguments and an extended finite-size scaling analysis, and by the existence of bounds for M.

Journal Article↗
PubMed2002

Mobilization and oxidative burst of neutrophils are influenced by carbohydrate supplementation during prolonged cycling in humans.

Prolonged, strenuous exercise may lead to suppressive effects on the immune system, which might be responsible for a greater susceptibility to opportunistic infections. The aim of this study was to examine the influence of carbohydrate substitution (CHS) during prolonged, strenuous exercise on neutrophil granulocytes and their oxidative burst (intracellular oxidation of dihydrorhodamine(123) to rhodamine(123) after induction by formylized 1-methionyl-1-leucyl-1-phenylalanin) using flow cytometry. In three trials different concentrations of CHS (placebo compared to 6% and 12% CHS; 50 ml.kg(-1)) were given randomly to 14 endurance trained cyclists [mean (SD) age 25 (5) years, maximal oxygen uptake 67 (6) ml.min(-1).kg(-1)] cycling for 4 h in a steady state at 70% of their individual anaerobic threshold. Blood samples were taken before, immediately after cessation, 1 h and 19 h after exercise. A significant rise in neutrophil counts was observed immediately after cessation and 1 h after exercise with a return to normal rest values 19 h after exercise for all three conditions ( P<0.001). The relative proportions of rhodamine(123)+ neutrophils were significantly diminished in all three conditions 1 h after exercise ( P<0.01), while the mean fluorescence intensity was lowest in the placebo trial and differed significantly to the 12% CHS trial ( P=0.024) and almost significantly to the 6% CHS trial ( P=0.052). In conclusion, these data suggest a beneficial effect of CHS on the neutrophil oxidative burst and a possible attenuation of the susceptibility to infections, presumably due to the reduction of metabolic stress in prolonged, strenuous exercise.

Adult↗
PubMed2002

HHV-8 DNA in blood and the development of HIV-associated Kaposi's sarcoma in the era of HAART--a prospective evaluation.

OBJECTIVE: To explore the significance of HHV-8 viremia in HIV-positive individuals for the risk of developing Kaposi's sarcoma (KS) in the era of highly active antiretroviral therapy. METHODS: 237 HIV-positive patients were included in this prospective evaluation and followed over an average duration of 34 months. HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were determined. In addition AIDS-defining conditions and antiretroviral therapy were documented of all participating subjects. RESULTS: HHV-8 DNA was detectable in PBMCs of 12.6% out of all individuals. 53.3% of these patients initially complained about KS, although 9.2% of patients without HHV-8 DNA in PBMCs were found on KS as well. Furthermore, four patients in total were observed with newly developed KS during follow up visits. None of these patients were noted with detectable HHV-8 DNA at their initial evaluation. CONCLUSIONS: Prevalence of HHV-8 DNA in PBMCs of subjects in this investigation was quite similar to former investigations. However, new diagnosed KS occurred less frequently than demonstrated in previous studies. All of those observed patients with new KS manifestations were negative for HHV-8 DNA in PBMCs at study entry. This observation differs from earlier studies which have postulated the detection of HHV-8 DNA in PBMCs as a predictive value for development of KS. Due to results as presented, a single HHV-8 DNA test in blood has no predictive value in support of predictability of KS development. With respect toto costs and to a less complicated performance antibody assays should be preferred.

Adult↗
PubMed2002

Double mutant studies identify electrostatic interactions that are important for docking cytochrome c2 onto the bacterial reaction center.

Cytochrome c2 (cyt) is the mobile electron donor to the reaction center (RC) in photosynthetic bacteria. The electrostatic interactions involved in the dynamics of docking of cyt onto the RC were examined by double mutant studies of the rates of electron transfer between six modified Rhodobacter sphaeroides RCs in which negatively charged acid residues were replaced with Lys and five modified Rhodobacter capsulatus Cyt c2 molecules in which positively charged Lys residues were replaced with Glu. We measured the second-order rate constant, k2, for electron transfer from the reduced cyt to the oxidized primary donor on the RC, which reflects the energy of the transition state for the formation of the active electron transfer complex. Strong interactions were found between Lys C99 and Asp M184/Glu M95, and between Lys C54 and Asp L261/Asp L257. The interacting residues were found to be located close to each other in the recently determined crystal structure of the cyt-RC complex [Axelrod, H., et al. (2002) J. Mol. Biol. (in press)]. The interaction energies were approximately inversely proportional to the distances between charges. These results support earlier suggestions [Tetreault, M., et al. (2001) Biochemistry 40, 8452-8462] that the structure of the transition state in solution resembles the structure of the cyt-RC complex in the cocrystal and indicate that specific electrostatic interactions facilitate docking of the cyt onto the RC in a configuration optimized for both binding and electron transfer. The specific interaction between Asp M184 and Lys C99 may help to nucleate short-range hydrophobic contacts.

Cytochrome c Group↗
PubMed2002

Monitoring of endogenous interferon-alpha and human herpesvirus 8 in HIV-infected patients with Kaposi's sarcoma.

The incidence of AIDS-associated Kaposi's sarcoma has declined since the mid-nineties due to the availability of potent antiretroviral therapy including protease inhibitors. However, Kaposi's sarcoma is still the most common neoplasia in HIV-infected patients. In the pathogenesis of the HIV-associated as well as other forms of this disease an infectious agent seems to play a role, namely the human herpesvirus 8. Even before the discovery of the HIV virus, high levels of an unusual acid-labile form of endogenous interferon alpha were found in patients with AIDS-associated KS. The administration of recombinant interferon alpha evolved as standard therapy for Kaposi's sarcoma in HIV-infected patients with a moderate immunodeficiency in addition to antiretroviral therapy. This investigation monitored the levels of HHV 8 and endogenous interferon in 4 patients with and without Kaposi's sarcoma during the course of HIV-disease. The results of our experiments lead us to two hypotheses: First of all, the pre-therapeutic level of endogenous interferon may be a predictor of the response to an interferon-alpha therapy for HIV-associated Kaposi's sarcoma. Secondly, the determination of HHV 8 DNA in blood of HIV-positive patients may allow conclusions about the risk for the development of Kaposi's sarcoma. However these hypotheses should be tested by monitoring the levels of endogenous interferon and HHV 8 DNA in clinical studies of a greater number of HIV-infected patients.

Adult↗
PubMed2002

Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment.

Transplantation of solid organs has been well established as a mode of therapy for the treatment of various end-stage organ diseases for many years. Up to now, it has benefited more than 1 million patients worldwide. The long-term success of organ transplantation depends particularly on the prevention of allograft rejection. Various regimens have been used to suppress hosts' cellular immune responsiveness to the grafted organs. Nowadays immunosuppressive therapies consist mainly in prednisolone, azathioprine, cyclosporine, anti-T-lymphocyte-globulin (ATG), anti-CD 3 antibody (OKT3) and substances of a new generation, such as tacrolimus or mycophenolic acid. However, not only the patient's reactivity to the graft is impaired, but also that to infectious organisms. Chronically altered immune responsiveness is especially associated with a dramatically increased risk of malignancy, most frequently non-Hodgkin's lymphoma and skin cancer. Within the first 5 years of immunosuppression 40% of transplant recipients experience premalignant skin tumors such as actinic keratoses and Bowen's disease, and also such skin cancers as squamous cell carcinomas and basal cell carcinomas. Quite often these have an aggressive biology and an uncommon morphology. Cancer is now responsible for a mortality rate of 5-8% in organ transplant patients. Various risk factors, such as exposure to sun and infections with oncogenic viruses (e.g. HPV) contribute to the already increased risk of dysplasia when lifelong immunosuppression is required. Prophylactic strategies therefore include the development of virus-like particles (VLPs) as anticancer vaccines, which might become a very interesting approach to preventing HPV-associated cancer. The prevention of precancerous conditions and mature skin cancers in grafted patients includes protective clothing and adequate protection of UV-exposed skin regions, including lips, from sunlight with appropriate sunscreen. Close dermatological surveillance through a specialized outpatient department should be ensured to detect potentially fatal skin malignancies at an early stage. Early treatment of precancerous lesions includes topical retinoids, such as tretionin, tazarotene or adapalene. A 5% fluorouracil cream is widely used but shows variable effects on manifest actinic keratoses. As cellular immunity seems to play the major part in the prevention and cure of malignant and premalignant cutaneous neoplasias as well as viral infections, a specific enhancement of the local immunity would be desirable. Imiquimod is one of a class of agents known as immune response modifiers. The drug has been shown to have both antiviral and antitumor activity. Application of immune response activators or modifiers such as imiquimod might be premising in the case of transplant recipients.

Humans↗
PubMed2002

[The surgeon as a cost factor. Cost analysis exemplified by surgical treatment of rectal carcinoma].

INTRODUCTION: Besides quality, costs play an increasingly important role. For rectal carcinoma, the cost of the surgical treatment of the disease (including after-care) was analysed under variable clinical conditions. METHODS: Eleven patients (eight men, three women, median age 57 years) with curative resection of rectal carcinoma between 1991 and 1995 were selected: Five patients with an uneventful course remaining recurrence-free, three patients who developed an anastomotic leakage and three patients with locoregional recurrence during their further course. In three patients, adjuvant radiochemotherapy was performed after resection of the primary tumor. For each patient, costs from the first postoperative day until the end of an assumed after-care of 5 years' duration were analysed. RESULTS: Costs for the postoperative period of the primary treatment ranged between 3.162 DM and 149.988 DM, in case of development of an anastomotic leakage between 14.699 DM and 149.988 DM. Adjuvant radiochemotherapy increased costs by 12.265 DM up to 23.259 DM, locoregional recurrence caused additional costs between 9.461 DM and 27.301 DM. Cost group analysis showed the costs for nursing care to be the highest (30% of total costs), followed by the expense for drugs and medication. Total costs of treatment ranged from 7.361 DM to 160.833 DM. CONCLUSIONS: Costs as well as the patient's prognosis depend to a great extent on the quality of the procedure and consequently on the individual operating surgeon. A complicated course is associated with a considerable increase in costs. A complete cost analysis of rectal carcinoma has to include the cost of a potential locoregional recurrence which would lead to the additional prolonged after-care for these patients.

Adult↗
PubMed2002

[Skin diseases in organ transplant patients].

In Germany 3273 visceral organs were transplanted in the year 2000. Together with patients grafted abroad, it is estimated that between 70,000 and 100,000 organ transplant patients are currently living in Germany. With the provision of lifelong immunosuppression the survival-time of these patients can exceed more than 20 years. In the first year following transplantation special emphasis is given to the prevention of viral, bacterial and fungal infections. Regular dermatological screening can provide early diagnosis of even systemic infections. An increased incidence of skin cancer parallels the extended survival rates of grafted patients. Within the first 5 years of immunosuppression 40% of these patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell carcinomas show an aggressive biology and an uncommon clinical morphology. The increased incidence of cancer is now responsible for a mortality rate of 5-8% in grafted patients. Against a background of lifelong immunosuppression, other risk factors include sun exposure and infections with oncogenic viruses. The rapidly growing numbers of allograft recipients as well as the rising long term survival rates of these patients demand the provision of high quality interdisciplinary and dermatological care in this field.

Humans↗