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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 55 records · Page 3Linked to original sources
PubMed2005

Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation.

The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.

Alginates↗
PubMed2005

Real-time 3-D dark-field microscopy for the validation of the cross-linking process of alginate microcapsules.

Alginate-based microencapsulation is a promising method for long-term maintenance of cellular and membrane function of the cells and tissue fragments required for in vitro and in vivo biosensors, for tissue engineering and particularly for immunoisolation of non-autologous transplants. Microcapsules of high mechanical strength and optimum permeability can be produced by injection of BaCl2 crystals into alginate droplets before they come into contact with external Ba2+. A key requirement is that the system parameters (number of crystals, speed of the crystal stream etc.) are properly adjusted according to the mannuronic and guluronic acid ratio and the average molecular mass of the alginate as well as to the diameter of the microcapsules. Robust, reliable, rapid and low-cost validation tools are, therefore, needed for assurance of the microcapsule quality. Here, we describe a novel three-dimensional (3-D) dark-field microscopy that allows the real-time measurement of the number and spatial distribution of the injected Ba2+ ions throughout the microcapsules after treatment with sulphate. This novel method requires only a conventional microscope equipped with three polarising filters and a double aperture stop. In contrast to confocal laser scanning microscopy images, peripherally attached BaSO4 precipitates can clearly be distinguished from internal ones. The data also demonstrate that several steps of the alginate gelling process must be improved before such immunoisolation can be used in patients.

Alginates↗
PubMed2005

[Minimally invasive surgery for morbid obesity--evidence or fashion?].

In the last decades surgical treatment for morbid obesity has emerged from being the interest of only few surgeons to a well recognized surgical specialty. This development was promoted by the dramatic increase of prevalence of obesity and the development of laparoscopic surgical techniques. In 1996 the NIH consensus conference stated that bariatric surgery is the most effective therapy to treat obesity and type 2 diabetes, whereas conservative treatment strategies failed in the long-term. Only few studies have compared the different operative strategies. It has been shown that the bypass procedure is better than gastric banding with respect to weight loss and the decrease of comorbidities, but suffers from more short-term morbidity. In recent years, randomized trials have been published comparing laparoscopic with open procedures. These studies show an advantage for the laparoscopic techniques. This paper gives a critical overview on bariatric surgery and summarizes the current literature in this speciality.

Bariatrics↗
PubMed2005

[Islet transplantation in type I diabetes mellitus].

Type 1 diabetes mellitus results from autoimmune destruction of the insulin-secreting cells in the pancreas. The dramatic breakthrough in 2000 with the "Edmonton protocol" for successful solitary islet transplantation has restored optimism for the application of islet transplantation as a treatment for type I diabetes. Due to the recent successes, islet transplantation has evolved from a theoretical concept to its current status as a therapeutic option for patients with type 1 diabetes. Islet transplantation has shown to normalize metabolic control in a way that has been virtually impossible to achieve with exogenous insulin. The less invasive procedure of islet transplantation as compared to whole pancreas transplantation in patients with type 1 diabetes mellitus would be expected to be safer and much less costly. However, this procedure also requires lifetime immunosuppression with drugs. The limited availability of donor organs and the necessity of transplantation of several pancreata in order to achieve insulin independence limit this procedure to a small minority of patients. Unlike the North American centers, the European centers concentrated their efforts on islet after kidney and simultaneous islet kidney transplantation. The two Swiss islet transplantation programs have been pioneers in applying the steroid-free "Edmonton protocol" to simultaneous islet-kidney and islet after kidney transplantation. The long term follow-up showed that islet function decreases over time. In order to maintain insulin independence repeated islet transplants would have to be given to the patients. Therefore, there has been a change in paradigm over time. The major goal of islet transplantation focuses now on achieving a good blood glucose control and avoidance of severe hypoglycaemic episodes rather than only insulin-independence. Thus, due to the limited supply of donor organs, more patients can benefit from islet transplantation. Small insulin doses of exogenous insulin prevent stress on the islet in particular after meals and might help to maintain the transplanted islet mass over time. Due to the severe limitations of immunosuppression solitary islet transplantation is limited to a very small number of patients with type 1 diabetes. The most common indication for islet transplantation in Switzerland is terminal kidney failure in patients with type I diabetes. A simultaneous islet-kidney or pancreas-kidney transplantation should be offered to these patients. The choice between islet or pancreas transplantation is a matter of age and diabetic complications because the perioperative risk is considerably higher in pancreas transplantation.

Diabetes Mellitus, Type 1↗
PubMed2005

Ciprofloxacin-induced acute generalized exanthematous pustulosis mimicking bullous drug eruption confirmed by a positive patch test.

We report the case of an 80-year-old woman presenting with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP) confirmed by a positive patch test. Cutaneous morphology, course and histological findings were consistent with a definite diagnosis according to the AGEP validation score of the EuroSCAR study group. We point to the rarity of quinolone-induced AGEP and discuss immunological mechanisms, the value of in vivo and in vitro tests as well as the main differential diagnosis. Furthermore, we highlight in this particular case the challenging differentiation from bullous drug eruption.

Aged, 80 and over↗
PubMed2005

Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced systemic disease in cats, characterized by granulomas in organs and granulomatous vasculitis. This study describes the morphologic features of granulomatous vasculitis in FIP as well as its development in the course of monocyte-associated feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in situ hybridization, and electron micropscopy. Granulomatous phlebitis at different stages of development was observed. Vasculitic processes ranged from attachment and emigration of FCoV-infected monocytes to vascular/perivascular granulomatous infiltrates with destruction of the vascular basal lamina. Monocytes as well as perivascular macrophages were activated because they were strongly positive for CD18 and expressed cytokines (tumor necrosis factor-alpha and interleukin-1beta) and matrix metalloproteinase-9. In addition, general activation of endothelial cells, represented by major histocompatibility complex II upregulation, was observed in all cases. These results confirm FIP as a monocyte-triggered systemic disease and demonstrate the central role of activated monocytes in FIP vasculitis.

Animals↗
PubMed2004

[Ethical decision-making at the end of life--knowledge and attitudes of medical students].

BACKGROUND AND OBJECTIVE: Physicians are often confronted with ethical and legal questions at the end of life. In this study we asked medical students at the universities of Mainz and Berlin (Charité) about the "Guidelines on Physicians' Aid to the Dying" issued by the German Medical Association: their moral attitude and legal knowledge regarding the limitation of medical procedures at the end of life and their judgement about the quality of medical education on these topics. METHODS: 569 medical students in their 1. and 4. clinical semester as well as the final year of their studies in Mainz and students in their 5. year of studies in Berlin received a questionnaire containing 14 items relating to ethical and legal questions at the end of life. RESULTS: 308 (54.1%) completed the questionnaire. 7.8% knew the contents of the "Guidelines on Physicians' Aid to the Dying". Between 10% (use of catecholamines) and 62% (parenteral feeding) viewed withholding or withdrawing life-sustaining measures from dying patients as illegal. 39-72% held the view that measures of nutrition and hydration were part of the indispensable basic medical care for every patient. 12-26% were unsure with respect to their moral views about withholding and withdrawal of therapy. 82% felt insufficiently prepared for dealing with ethical questions at the end of life. CONCLUSION: Only a minority of medical students was informed about ethical principles and legal regulations regarding end-of-life decisions. Teaching of ethical and legal knowledge and integration of these issues into clinical problem solving should be mandatory.

Advance Directives↗
PubMed2004

Shoe rim and shoe buckle pseudotumor of the ankle in elite and professional figure skaters and snowboarders: MR imaging findings.

OBJECTIVE: To review MR imaging of figure skaters and snowboarders presenting with painful soft-tissue swelling of the lateral supramalleolar region with a clinical provisional diagnosis of soft-tissue tumor. DESIGN AND PATIENTS: MR imaging was prospectively reviewed by two sub-specialized musculoskeletal radiologists. The findings were correlated with a second clinical review and examination of the shoe wear. The patients were four female athletes undergoing heavy training regimes, ranging in age between 16 and 25 years. Two patients were elite figure skaters, and two were professional snowboarders. Three patients had unilateral masses with pain, and one patient presented with bilateral clinical findings. RESULTS: MR imaging showed subcutaneous, focal soft-tissue masses of the supramalleolar region in five ankles at the same level above the ankle joint. MR imaging prompted a second clinical review and correlation with the shoe wear. The MR imaging findings correlated to the level of the shoe rim or shoe buckle in all patients, confirming the suspected MR imaging diagnosis of an impingement syndrome. All four sportswomen were training excessively, ignoring safety advice regarding training duration, timing of breaks, and shoe wear rotation. CONCLUSION: Ice skaters and snowboarders may present with persistent and disabling pain. On MR imaging, this corresponds to a focal soft-tissue abnormality, which may be due to subcutaneous fat impingement between the fibula and the shoe rim or shoe buckle.

Adolescent↗
PubMed2004

Laser scanning tomography of the optic nerve vs CSF opening pressure in idiopathic intracranial hypertension.

The authors investigated 17 patients with idiopathic intracranial hypertension (IIH), correlating laser scanning tomography of the optic nerve with CSF opening pressure. The decrease in papilla volume and papilla height showed a linear correlation with the opening pressure of the CSF (r = 0.59, p < 0.001; r = 0.63, p < 0.001). If the CSF opening pressure is higher than 20 cm water, an increase of 5 cm water CSF pressure corresponds to a papilla volume increase of 0.95 mm3 as well as a papilla height increase of 0.34 mm.

Adult↗
PubMed2004

Circadian patterns of neurotransmitter related gene expression in motor regions of the rat brain.

Mammalian motor activity displays circadian patterns in normal behaviour and in many movement disorders, like levodopa responsive dystonia and Parkinson's disease. Here, we hypothesized that a circadian pattern of dopamine synthesis would trigger rhythms in the expression of genes in regions receiving dopaminergic innervation. Indeed tyrosine hydroxylase and cholecystokinin mRNA were upregulated in the substantia nigra and ventral tegmental area in the course of the day. However, in the caudate putamen, the mRNA levels, for dopamine D2 and adenosine 2A receptor, dynorphin, and substance P were lower during the day than during the night, whereas the expression of dopamine D1 receptor, enkephalin, and somatostatin was stable. In the frontal cortex, a clear midday peak of enkephalin expression was detected, while cholecystokinin and vasoactive intestinal peptide expression did not vary. Clear circadian gene expression patterns can therefore be demonstrated in brain regions involved in motor regulation, but they do not follow a simple dopaminergic drive and more complex regulatory patterns have to be assumed.

Animals↗
PubMed2004

[Diagnosis and therapy of acute complaints after "whiplash injury" in Germany. Results of a representative survey at surgical and trauma departments in Germany].

Whiplash injury of the cervical spine is a relevant medical and socioeconomic problem, which is still the subject of controversy. We performed a survey to evaluate the current status of diagnostics, classification, treatment, and doctors' subjective opinions at surgical and trauma departments in Germany. A total of 1568 hospitals were addressed to answer a standardized questionnaire on their proceedings and opinions concerning whiplash injury. We received 540 (34.44%) completed questionnaires. There was overall agreement concerning the need for physical examination. The radiological assessment included an a.p. and a lateral plain X-ray of the cervical spine in 82.6%. The indication for functional X-rays in flexion/extension was inconsistent. On average they were performed in 39.1% of all patients. In most cases (68.9%) whiplash injury was not classified; 13.2% of doctors used the classification according to the Quebec Task Force and 13.9% according to Erdmann. A cervical collar was prescribed in 85%. While 30% of patients received only a cervical collar, 55.6% underwent additional physiotherapy. Only 8.3% were treated by physiotherapy without immobilization. The doctors' subjective opinions indicated psychological factors to be important for long-lasting problems, but not for the acute period of complaints. There is no homogeneous concept for diagnostics, classification, and treatment of patients who suffered a whiplash injury in Germany. This situation reflects the current problems in management of this condition. Scientific evidence for functional treatment to avoid adverse influence of immobilization by cervical collars has not yet been transferred to our daily routine in Germany.

Germany↗
PubMed2004

[Giant cell tumor of bone with rapid malignant course].

The case of a 28-year-old male patient with a locally aggressive lesion of the distal tibia is presented. Following the diagnosis of giant cell tumor of bone (GCT) on biopsy and curettage, a rapid malignant course was observed with recurrence 2.5 months later. Multiple metastases appeared 6 months after initial presentation. Following initial chemotherapy according to the COSS protocol and later with carboplatin and VP-16, therapy was changed to Adriamycin and later gemcitabine due to progressive disease. Good palliation was achieved, and the patient felt well with less shortness of breath on exertion and was ambulatory with walking aids. The malignant nature of the tumor was not detected in the initial pathologic examinations. Review of the pathologic material provided histologic clues permitting the diagnosis of a primary malignant GCT with a fibrohistiocytic/fibrosarcomatous component. Malignancy in a giant cell tumor is a much debated diagnostic dilemma when a frank sarcomatous component is lacking. Cytologic atypias and flame-like tufts of infiltration of soft tissue are important clues. Surgical treatment should be commensurate. Monotherapy with Adriamycin or gemcitabine can be considered in order to inhibit the disease progression.

Adult↗
PubMed2004

[Cardiopulmonary exercise capacity increases after interventional ASD-closure].

BACKGROUND: In patients with atrial septal defects of the secundum-type (ASD), exercise tolerance is reduced. Generally, ASD closure is recommended in symptomatic patients and in patients with a relevant left-to-right shunt (Qp/Qs > 1.5). Only few data are available concerning objective parameters of cardiopulmonary exercise capacity. The aim of this study was to evaluate exercise capacity as achieved by ergospirometry in adult patients with an ASD at baseline and in the long-term following transcatheter closure. METHODS AND RESULTS: Thirty consecutive patients (8 male; mean age 43.4 years; defect size 23.5 mm; pulmonary-to-systemic flow ratio (Qp/Qs) 1.94) performed exercise testing on a supine bicycle ergometer. At baseline, oxygen consumption at maximal exercise (VO(2) peak) was 14.3 ml/min kg, oxygen consumption at the anaerobic threshold (VO(2)-AT) was 11.2 ml/min/kg and maximal achieved workload was 86 Watt. At one and six months after ASD-closure, there was no relevant increase of the VO(2) peak, the VO(2)-AT or the maximal workload. After 12 months, there was a significant increase of the VO(2) peak (15.1 ml/min/kg, p = 0.049), the VO(2)-AT (13 ml/min/kg, p < 0.001) and the maximal workload (99 Watt, p < 0.01). An increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT) could be seen in 24 out of 30 patients and was independent of shunt volume (Q(p)/Q(s) < or = 2, 1.95 ml/ min/kg; Q(p)/Q(s) > 2, 2.13 ml/min/ kg; ns), defect size (defect < or = 24 mm, 2.0 ml/min/kg; defect > 24 mm, 1.5 ml/min/kg; ns), age (age < or = 44 years, 1.97 ml/min/kg; age >44 years, 1.66 ml/min/kg; ns), gender (female 1.56 ml/min/ kg; male 1.91 ml/min/kg; ns) and of the existence of a residual shunt. Highly symptomatic patients had a tendency to have greater benefit from ASD-closure as compared to mildly symptomatic patients (NYHA 0/I 1.85 ml/min/kg; NYHA II 1.5 ml/min/ kg; NYHA III 2.7 ml/min/kg; ns). There was no correlation between shunt volume, shunt size, pulmonal arterial pressure and increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT). CONCLUSION: There is no relevant improvement in exercise capacity early (1-6 months) after interventional ASD-closure, but late after ASD-closure (12 months) exercise capacity improves significantly. This improvement can be found in almost all patients independent of gender, age, symptoms, shunt volume and defect size.

Adolescent↗
PubMed2004

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction. Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial.

BACKGROUND: Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. METHODS: We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti- Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. RESULTS: There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG kappa = 0.611 (95% CI = 0.498-0.724, p < 0.001) and for IgA kappa = 0.431 (95% CI: 0.322-0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti- C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). CONCLUSION: Depending on the test system used, there are large differences in the prevalence of anti- C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

Anti-Bacterial Agents↗
PubMed2004

Alveolar echinococcosis of the liver in an adult with human immunodeficiency virus type-1 infection.

We describe a patient with human immunodeficiency virus type-1 (HIV) infection and alveolar echinococcosis (AE) with a focus on two messages. Despite being severely immunocompromised over years the patient exhibited a long-term asymptomatic course of AE. This is in clear contrast to reports describing accelerated courses of AE in immunocompromised patients. The patient had therapeutic mebendazole drug levels with only 1/10 of the normal drug dose. He was co-treated with protease inhibitors for his HIV infection. These drugs are known as strong inhibitors of cytochrome P450 3A4 (CYP3A4)-dependent metabolism. We speculate that benzimidazoles and protease inhibitors interfere at the CYP3A4-level. The first report of co-infection of HIV and accelerated AE was in a young girl with an extremely low CD4 cell count and an abrogated lymphoproliferative responsiveness to parasite antigen stimulation. Since the CD4 cell count in our patient remained in the range of 27-150 cells/microl, we speculate that there was a critical threshold of immunosupression for constraining AE. Initial treatment with albendazole for AE added to the current highly active antiretroviral treatment (HAART), and suppressive toxoplasmosis therapy became complicated by pancytopenia. After full recovery of the bone marrow, mebendazole was introduced with a new HAART and the previously prescribed toxoplasmosis maintenance therapy. Surprisingly, efficient mebendazole levels were achieved with an uncommonly low dose. These observations suggest that the benzimidazoles, albendazole and mebendazole, may interact with protease inhibitors, which are known for their strong inhibition of the CYP3A4.

AIDS-Related Opportunistic Infections↗
PubMed2004

Finite element and experimental analyses of polymer-based dental bridges reinforced by ceramic bars.

Dental bridges made of polymer materials reveal only low loading capacity. This paper analyzes possible improvements of the loading capacity of polymer-based dental bridges reinforced by incorporated ceramic bars. Finite element (FE) analyses were performed to study the stress distribution caused by the mastication process in the bridge material. In the experimental part of the study, the fracture load of dental bridges with and without ceramic bar reinforcement was evaluated. Critical stresses occur in the connector area between abutment and pontic of bridges without bar reinforcement. A suitably shaped ceramic bar incorporated into the polymer-based bridge can significantly reduce these critical stresses. The fracture load of the bridge was increased from 515 to 1603N by the bar reinforcement. We conclude from our study that a ceramic bar can significantly improve the loading capacity of a polymer-based dental bridge. The FE and the experimental analyses revealed that the detailed design of the ceramic bar is of decisive importance for the effectiveness of the suggested ceramic reinforcement.

Bite Force↗