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Biomedical subjects

U Martin

Publications and source records attributed to U Martin.

At least 19 recordsLinked to original sources
PubMed2006

A clinical study on the tolerability of a liposomal povidone-iodine nasal spray: implications for further development.

PURPOSE OF STUDY: This phase I study assessed tolerability and local effect of a liposome dispersion with povidone-iodine (polyvinylpyrrolidone-iodine, PVP-I) as nasal spray. PROCEDURES: Three groups received liposomal dispersion with PVP-I (2.2, 4.4 and 0% as control) in single and repeated use (3 days, three times a day). A set of functional and cytological tests as well as safety assessments were performed. RESULTS: No safety-relevant finding or serious adverse events were reported, no evidence for cyto- nor genotoxicity obtained. No clinically relevant changes in mucosa appearance, nor in olfactory sense, nor in ciliary activity (sensitive indicator of local tolerance) occurred and no complaints about nasal airflow obstruction were observed. All liposomal formulations had a positive effect on the nasal mucosa, challenged by allergy in some volunteers. CONCLUSIONS AND MESSAGE: Application of liposomal PVP-I spray to the nasal mucosa does not result in any demonstrable limitation of the nasal function nor in detectable damage to the multilayer ciliated epithelium of the nose. Improvement of various parameters of nasal function under liposomal PVP-I suggest improved mucociliary clearance. Explanation could be humidification, improved surfactant (phospholipid) level and/or sufficient mucolytic activity of iodide due to local application of the constituents.

Administration, Topical↗
PubMed2006

Clinically applicable 7-Tesla magnetic resonance visualization of transplanted human adult stem cells labeled with CliniMACS nanoparticles.

BACKGROUND: Intra-myocardial transplantation of bone marrow derived cells is currently under clinical evaluation as a therapy for heart failure. A major limitation of all clinical studies for myocardial restoration through cell transfer is the inability to track the fate of the transplanted cells. We present a clinically applicable technique using advanced ultra high-field 7-Tesla (7T) magnetic resonance imaging (MRI) of nanoparticle-labeled transplanted human EPCs in porcine ischemic hearts. METHODS: CD133 positive cells were isolated from bone marrow by magnetic bead selection. Positive cells (5 - 8 x 10 (6) cells) were transplanted into porcine ischemic myocardium (n = 8). Control animals (n = 3) received a medium injection. MRI on a 7T scanner was performed to demonstrate the distribution of the EPCs. RESULTS: CD133+ cells were identified on gradient echo images (T(1)-weighted) within the myocardium 4 weeks after transplantation. CONCLUSIONS: Magnetically labeled EPCs transplanted for therapeutic neovascularization or reduction of infarct size in myocardial ischemia can be visualized by MRI at high-field strengths.

Adult Stem Cells↗
PubMed2006

[In vivo detection of integration of grafted cells after myocardial transplantation].

Myocardial transplantation of myocytes and bone marrow derived cells is currently under clinical evaluation as an alternative therapy of heart failure. One of the main problems of all clinical studies performed so far is the inability to track the fate of the transplanted cells. The aim of our study was the development of a potentially clinically applicable approach, which allows for detection of the transplanted cells without need for collection of tissue samples. Fetal canine cardiomyocytes were labelled with the non-toxic fluorescent membrane dye Vybrant CM-DiI and delivered into the free wall of the left ventricle of adult mongrel dogs. For subsequent tracking of the cellular graft, the dogs underwent a second operation in which an intra-vital microscope was mounted above the exposed heart within the thorax. A special computer software eliminated artefacts caused by myocardial contraction. Two months after transplantation, the fluorescent graft was macroscopically visible by intra-vital microscopy using a 10x magnification. Histological studies served as microscopic control and confirmed the existence of DiI-labelled cells at the site of injection. Connexin 43 immunoreactivity was visible at junctional complexes between donor and recipient cells, suggesting morphologic and functional coupling as a result of gap junction formation. Our results demonstrate that in vivo detection of transplanted cells in the heart is feasible. Further technical adjustments should allow for thoracoscopic/endoscopic application of this method, making it appropriate for use in other organs and in clinical studies.

Animals↗
PubMed2006

Isolation of bovine cardiomyocytes for reprogramming studies based on nuclear transfer.

The goal of this study was to establish and validate a protocol for preparing bovine cardiomyocytes from slaughterhouse material for nuclear transfer experiments. The cardiomyocyte was selected because it is a terminally differentiated cell and strongly expresses a unique subset of genes which can be monitored during the reprogramming period. A total of 39 trials were conducted, and an optimized protocol was developed yielding individual contractile cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves stabilization of bovine heart tissue for transportation from the slaughterhouse to the laboratory by perfusion with Custodiol. This was followed by an enzymatic dissociation with collagenase in calcium-free medium and yielded individual contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the cardiomyocytes to round up which was an essential pre-condition for drawing them into glass transfer pipettes for delivery into the perivitelline space and for efficient electrofusion with cytoplasts derived from in vitro matured bovine oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear transfer, resulted in a significantly reduced proportion of blastocysts compared to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees C prior to nuclear transfer was not compatible with blastocyst development. It is expected that this system will be valuable for investigating the reprogramming of gene expression which occurs after somatic cell nuclear transfer.

Animals↗
PubMed2006

Effect of treatment with nebivolol on parameters of oxidative stress in type 2 diabetics with mild to moderate hypertension.

AIM: The aim of this study was to examine the effect of the cadioselective B(1)-adrenoceptor blocker nebivolol on glycaemic control, lipid profile and markers of oxidative stress in patients with type 2 diabetes over a 6-month period. METHODS: Twenty-six patients with mild to moderate hypertension (140-160 mmHg systolic, 90-105 mmHg diastolic) confirmed on 24-h blood pressure monitoring, were treated with nebivolol 5 mg daily for 6 months. Total serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) subfractions, lipid hydroperoxides (LHPs) and total antioxidant capacity (TAC) were measured before and after 6 months of treatment. RESULTS: Nebivolol, as expected, reduced mean daytime systolic and diastolic pressures on ambulatory monitoring (149 +/- 9 to 140 +/- 13 mmHg, P = 0.02 and 84 +/- 7 to 77 +/- 9 mmHg, P < 0.001). There were no significant changes in serum cholesterol or triglycerides following treatment but a significant increase in HDL cholesterol was noted (1.12 +/- 0.19 to 1.25 +/- 0.36 mmol/L, P = 0.008). Patients showed a highly significant reduction in TAC from 501 +/- 57 to 422 +/- 29 trolox equivalent (P < 0.001). Baseline LHPs were very high and showed no significant change over the 6-month period (18.7 +/- 7.4 and 18.7 +/- 10.9 micromol/L). The LDL score increased significantly from 1.7 +/- 0.7 to 2.3 +/- 0.7 (P = 0.0002) at 6 months suggesting a change to a more atherogenic lipid profile. Neither weight nor glycaemic control changed during treatment. CONCLUSION: Nebivolol appears to be lipid neutral and may even have a positive effect on HDL cholesterol. Despite this it may promote the formation of potentially atherogenic LDL subfractions possibly as a result of reduced antioxidant defences. Further studies are needed to clarify the changes observed in parameters of oxidative stress.

Antihypertensive Agents↗
PubMed2005

Shuttle of lentiviral vectors via transplanted cells in vivo.

Lentiviral vectors have turned out to be an efficient method for stable gene transfer in vitro and in vivo. Not only do fields of application include cell marking and tracing following transplantation in vivo, but also the stable delivery of biological active proteins for gene therapy. A variety of cells, however, need immediate transplantation after preparation, for example, to prevent cell death, differentiation or de-differentiation. Although these cells are usually washed several times following lentiviral transduction, there may be the risk of viral vector shuttle via transplanted cells resulting in undesired in vivo transduction of recipient cells. We investigated whether infectious lentiviral particles are transmitted via ex vivo lentivirally transduced cells. To this end, we explored potential viral shuttle via ex vivo lentivirally transduced cardiomyocytes in vitro and following transplantation into the brain and peripheral muscle. We demonstrate that, even after extensive washing, infectious viral vector particles can be detected in cell suspensions. Those lentiviral vector particles were able to transduce target cells in transwell experiments. Moreover, transmitted vector particles stably transduced resident cells of the recipient central nervous system and muscle in vivo. Our results of lentiviral vector shuttle via transduced cardiomyocytes are significant for both ex vivo gene therapy and for lentiviral cell tracing, in particular for investigation of stem cell differentiation in transplantation models and co-cultivation systems.

Animals↗
PubMed2005

Use of moxonidine in elderly patients with resistant hypertension.

BACKGROUND: Treatment of hypertension in the elderly people reduces the risk of cardiovascular and cerebrovascular events. Effective treatment often will require the use of two or more antihypertensive agents. Elderly people are at increased risk of adverse events from medication because of physiological changes in pharmacokinetics and pharmacodynamics, polypharmacy and drug interactions. They might not tolerate conventional add-on regimens of antihypertensives as a result. OBJECTIVE: To investigate the use of the I1-imidazoline receptor agonist moxonidine as an 'add-on' agent in elderly patients with resistant hypertension. METHODS: We investigated the safety and efficacy of moxonidine (200-400 microg) in a group of elderly patients whose blood pressure (BP) control remained poor despite treatment with two or more antihypertensives. BP was assessed by ambulatory BP monitoring with Spacelabs oscillometric equipment (Model 90207) before and after 6 weeks of treatment with moxonidine used as an 'add-on' agent with the patients normal medication. RESULTS: Following treatment with moxonidine, the mean daytime systolic BP fell from 169.2 to 153.8 mmHg, a significant reduction of 15.4 +/- 8.9 mmHg (P = 0.003). The mean daytime diastolic BP fell from 91.6 to 84.2 mmHg, a reduction of 7.4 +/- 5.8 mmHg (P = 0.017). For the night-time readings, the systolic BP fell from 151.1 to 141.2 mmHg, a reduction of 9.3 +/- 9.3 mmHg (P = 0.05). The corresponding diastolic fall in BP was not significant (77.9-74.7 mmHg). The 24 h-readings showed a significant reduction in the mean systolic BP from 163.0 to 148.6 mmHg (P = 0.004). The mean diastolic BP also fell significantly from 87.2 to 80.2 mmHg (P = 0.013). Clinical BP readings also showed a significant reduction from 195.9 +/- 19.6 to 174 +/- 17.8 mmHg (P = 0.002) and 103.6 +/- 9.5 to 99.0 +/- 12.4 mmHg (P = 0.013) for systolic and diastolic readings respectively. Moxonidine was well tolerated in 11 of the14 patients. CONCLUSION: These results suggest that moxonidine might have a place as an 'add-on' treatment in elderly patients whose hypertension is poorly controlled despite treatment with two or more antihypertensive agents.

Aged↗
PubMed2004

Changes in plasma lipids and markers of oxidative stress in normal pregnancy and pregnancies complicated by diabetes.

The purpose of the present study was to determine changes in plasma lipids and markers of oxidative stress longitudinally in pregnancy complicated by diabetes compared with non-diabetic pregnancy. This was carried out by following a group of normal pregnant women (n=17) and groups of pregnant women with Type I diabetes (n=19), Type II diabetes (n=12) and gestational diabetes mellitus (n=12) throughout pregnancy, with sampling carried out at the end of each trimester. Serum total cholesterol and triacylglycerols (triglycerides) were determined using standard colorimetric techniques and low-density lipoprotein (LDL) subfraction profile by disc PAGE. Total antioxidant capacity (TAC) was determined by enhanced chemiluminescence and lipid hydroperoxides by the ferrous oxidation of Xylenol Orange method. Total cholesterol and triacylglycerols increased significantly throughout pregnancy in all groups, but there were no significant differences between normal and diabetic women with respect to either. The LDL score was significantly higher (P<0.001) in diabetic women compared with normal women at each point throughout pregnancy, although there were no significant differences between the diabetic groups. There was evidence of greater oxidative stress in diabetic compared with normal women throughout. Corrected TAC was significantly lower (P<0.001) in all diabetic women throughout pregnancy. In addition, lipid hydroperoxides were higher in all diabetic compared with normal women, particularly so in those with Type II diabetes (P<0.05). These changes may have important implications for diabetic women during pregnancy, as an elevated risk of pre-eclampsia is thought to reflect an oxidative stress-related mechanism. In addition, these changes may have important implications for the development of atherosclerosis and the long-term cardiovascular health of women with diabetes.

Adult↗
PubMed2004

[Surface disinfection in nursing homes--what is really happening? Study of control success in three Duisburg nursing homes].

The effectiveness of cleaning and disinfection of environmental surfaces was evaluated in three nursing homes using bacteriological monitoring. Samples from inmates (nose, throat and wounds) and surface cleaning equipment were also taken. Cleaning solutions, disinfectants and cleaning clothes were found to be highly contaminated in two of three institutions. Referring to the surfaces in some cases disinfection didn't reduce bacterial colony counts and seeded MRSA as a potential pathogen in one nursing home. Six MRSA-positive inmates and identical strains were registered in the environment. MRSA can be used as a marker organism to demonstrate effectiveness of cleaning. To achieve further improvement bacteriological monitoring can help in focussing special cleaning and disinfection related problems.

Bacterial Infections↗
PubMed2004

Testing the practical aspects of therapeutics by objective structured clinical examination.

Medical students need to have a sound theoretical knowledge of pharmacology and a training in the practical aspects of therapeutics in order to prescribe effectively, safely and rationally when they qualify. Students have traditionally sat written exams and the practical aspects have been largely ignored. At the University of Birmingham we set up an objective structured clinical examination (OSCE) style examination to test the practical aspects of therapeutics. Over the last 2 years, 434 students have been examined in this way to determine competency in various clinical skills including, for example prescription writing, the drawing up and giving of injections, setting up nebulizers, and patient counselling about drug effects. Over that time we found the therapeutics OSCE to be feasible and useful. It has demonstrated serious practical deficiencies that were not apparent from written examinations in some students' ability to prescribe and administer drugs. Since its introduction, performance in the OSCE has improved. Whether this will result in safer and more effective prescribing in the preregistration house officer year has not been formally evaluated but it appears that they approach this aspect of patient care with greater confidence than graduates from other schools.

Clinical Competence↗
PubMed2003

Cardiovascular risk in systemic lupus erythematosus--evidence of increased oxidative stress and dyslipidaemia.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which is not explained by traditional risk factors alone. This study aimed to investigate markers of oxidative stress, lipid metabolism and inflammation as potential cardiovascular risk factors in women with SLE. METHODS: Venous blood samples were taken from 53 female Caucasian patients with SLE and from healthy age- and sex-matched controls. Samples were analysed for markers of oxidative stress, lipid metabolism [including low-density lipoprotein (LDL) subfraction profile] and C-reactive protein (CRP). RESULTS: Female SLE patients had an atherogenic lipid profile characterized by raised total cholesterol and triglycerides, and the presence of small, dense LDL subfractions compared with healthy controls. These changes were associated with increased oxidative damage and a moderately raised CRP. CONCLUSIONS: The results provide evidence for free radical and inflammatory activity in SLE and suggest potential targets to reduce the risk of cardiovascular disease in these patients.

Adult↗
PubMed2003

No evidence for productive PERV infection of baboon cells in in vivo infection model.

OBJECTIVES: The discovery that pig endogenous retroviruses are infectious for human cells in vitro lead to vehement discussions about the possible risk of infection after clinical xenotransplantation. Since PERV transmission to non-human primate cells in vitro has been observed, similar to human cells, infection studies in non-human primates should represent the best model to analyze a potential PERV transmission after xenotransplantation. However, it is still open to discussion, whether non-human primate cells can be infected productively-similar to human cells- and whether those species are suitable to analyze PERV infection risks in vivo. METHODS: In vitro, only few cell types can be tested for susceptibility. We developed a pig to baboon cell transplantation model with special emphasis on B-cell effective immunosuppression, removal of anti Gal-alpha 1,3-Gal-antibodies, inhibition of the complement cascade and long term survival of transplanted cellular grafts. This model allows us to investigate in vivo, whether any baboon cell types may be permissive for productive PERV infection. The xenograft recipients were investigated for up to 535 days post transplantation. Gal-alpha 1,3-Gal-antibody and complement levels were monitored. Potential PERV transmission was analyzed, not only in PBMC, but in a variety of tissue samples as well as in serum and plasma samples by PCR, RT-PCR and by detection of RT-activity. Moreover, potential PERV specific immune responses were studied by a highly sensitive Western-Blot-assay. RESULTS: Despite several days of extremely low levels of Gal-alpha 1,3-Gal-antibody and complement, and despite of long term xenochimerism, no evidence for PERV infection was obtained in any of the tested tissues or in the tested serum samples. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.

Animals↗
PubMed2002

Paracetamol disposition in renal allograft recipients.

OBJECTIVE: To evaluate the disposition of paracetamol in renal allograft recipients. METHOD: Eight fasting renal allograft recipients were given 1 g soluble paracetamol orally. RESULTS: Paracetamol was absorbed rapidly, and the mean plasma half-life from 2 h to 8 h was 2.6 +/- 0.5 h. After that, disappearance of paracetamol from the plasma was slower. Both the glucuronide and sulphate conjugates of paracetamol had slow elimination half-lives of 15.1 +/- 8.8 h and 26.2 +/- 14.6 h, and there were residual amounts of both conjugates in the plasma at 24 h. The renal clearances of both conjugates were low (21 +/- 14.2 ml/min and 32.4 +/- 31.4 ml/min) and there was a significant negative correlation between total amount of paracetamol recovered in the urine in 24 h and serum creatinine (r = -0.89, P<0.01). CONCLUSION: Paracetamol disposition is abnormal in renal allograft recipients and seems to relate to abnormal renal function in these patients.

Acetaminophen↗
PubMed2002

Oxidative stress and normal pregnancy.

OBJECTIVE: To determine whether, in normal pregnancies, there is evidence of oxidative stress that is related to the lipid changes observed in pregnancy. DESIGN: Longitudinal study of healthy women having a normal pregnancy. Samples were obtained towards the end of each trimester and after 8 weeks postpartum. PATIENTS: Seventeen healthy women during a normal singleton pregnancy were compared with 12 healthy, non-pregnant women. MEASUREMENTS: Oxidative stress was determined by measuring total antioxidant capacity (TAC), uric acid and lipid hydroperoxides (LHP). Lipid status was evaluated by measuring total and high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein (LDL) subfractions. RESULTS: Pregnancy was associated with decreased TAC and uric acid in the first trimester, which gradually increased during pregnancy, reaching normal values during the postpartum period. LHP significantly increased towards the end of pregnancy. The changes observed in LHP were significantly correlated with increases in LDL subfraction profile. CONCLUSIONS: Late pregnancy was associated with the formation of susceptible, oxidisable particles (high LDL score) and an increase in oxidative damage. These biochemical changes may be relevant for the long-term cardiovascular health of women, especially those of high parity or those who are at high risk for cardiovascular disease (e.g. women with diabetes).

Adult↗
PubMed2002

Alternative venlafaxine kinetics in overdose.

UNLABELLED: The pharmacokinetics of venlafaxine in therapeutic doses is well established. It is metabolized by the cytochrome P450 enzymes including CYP2D6. The toxicokinetics in overdose is less well known. CASE REPORT: A 33-year-old Caucasian female who ingested 3.0 g venlafaxine, and 210 mg zolpidem. The patient remained symptomatic for the following 24 h. Plasma pharmacokinetic analysis demonstrated a prolonged elimination half-life of venlafaxine, estimated to be 15.3 h. We postulate that the patient was a slow metabolizer of substrates for CYP2D6, an enzyme known to exhibit polymorphism.

Adult↗
PubMed2002

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.

Animals↗