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Biomedical subjects

Markus Weber

Publications and source records attributed to Markus Weber.

At least 19 recordsLinked to original sources
PubMed2006

Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations.

OBJECTIVE: To examine corticomotoneuronal function in amyotrophic lateral sclerosis (ALS) patients carrying superoxide dismutase 1 (SOD1) mutations using peristimulus time histograms (PSTH). METHODS: Six I113T, 3 A4V, one G41D and one G114A patient were studied along with 21 healthy control subjects. Analyses included comparison with previously reported data from 8 D90A homozygous and 12 sporadic ALS (SALS) patients examined by the authors using identical methodology. RESULTS: Cortical threshold was significantly reduced in A4V patients (41.3%) compared to I113T (58%), SALS (57%) and D90A (71%) patients, as well as healthy controls (49.7%). Estimated excitatory postsynaptic potentials (EPSPs) were significantly larger in A4V patients (4.39 mV) compared to healthy controls (2.95 mV), I113T (2.71 mV) and SALS (2.39 mV) patients. Clinical features and PSTH parameters in I113T were similar to SALS, however, PSTH primary peaks (PP) were significantly more dispersed, 9.5 ms compared to 4ms in SALS. PSTHs from single G41D and G114A patients were unremarkable, apart from large EPSP amplitudes in the G114A patient. CONCLUSIONS: ALS patients with A4V and I113T SOD1 mutations have distinctive corticomotoneuronal changes that are different from those in D90A homozygous and SALS patients. SIGNIFICANCE: PSTH studies should be considered for future in vivo studies of SOD1 pathophysiology in ALS.

Adult↗
PubMed2006

Open and laparoscopic living donor nephrectomy in Switzerland: a retrospective assessment of clinical outcomes and the motivation to donate.

BACKGROUND: Laparoscopic living kidney nephrectomy is thought to be associated with reduced morbidity, when compared to open nephrectomy. The purpose of this study was to explore the impact of these techniques on donors' clinical outcomes, satisfaction and motivation to donate. METHODS: Clinical outcomes were retrospectively compared in 152 open (n = 71) or laparoscopic (n = 81) donor procedures. Donor satisfaction and motivation were assessed with a self-administered questionnaire. RESULTS: The complication rate was the same with both procedures and the majority of complications were mild. Laparoscopy was significantly less painful and resulted in an insignificantly faster return to active life. More than 80% of the donors volunteered to donate without pressure. Worries about future health status, pain or scars were not important in the decision to donate. Similarly, only 15% considered the surgical procedure as instrumental for their decision. Few donors currently worried about their health with one kidney and more than 95% of the donors in both groups stated that they would give their kidney again. CONCLUSIONS: Living donor nephrectomy is safe, regardless of the procedure used. Although the laparoscopic nephrectomy offers clear short-term benefits over the open nephrectomy, donors' satisfaction was excellent with both surgical approaches. Moreover, the type of procedure did not seem to influence their decision to donate.

Adult↗
PubMed2006

Twin probes as a novel tool for the detection of single-nucleotide polymorphisms.

Single-nucleotide polymorphisms (SNPs) are the most common form of DNA sequence variation. There is a strong interest from both academy and industry to develop rapid, sensitive and cost effective methods for SNP detection. Here we report a novel structural concept for DNA detection based on fluorescence dequenching upon hybridization. The so-called "twin probe" consists of a central fluorene derivative as fluorophore to which two identical oligonucleotides are covalently attached. This probe architecture is applied in homogeneous hybridization assays with subsequent fluorescence spectroscopic analysis. The bioorganic hybrid structure is well suited for sequence specific DNA detection and even SNPs are identified with high efficiency. Additionally, the photophysical properties of the twin probe were investigated. The covalent attachment of two single stranded oligonucleotides leads to strong quenching of the central fluorescence dye induced by the nucleobases. The twin probe is characterized by supramolecular aggregate formation accompanied by red-shifted emission and broad fluorescence spectra.

Biochemistry↗
PubMed2006

Pamidronate does not adversely affect bone intrinsic material properties in children with osteogenesis imperfecta.

Cyclical intravenous pamidronate therapy increases bone mass in children with osteogenesis imperfecta (OI), but the effect on the intrinsic material properties of bone is unknown at present. Thus, a possible influence of pamidronate treatment on bone quality at the material level might negate the beneficial effects of the gain in bone mass and lead to bone fragility in the long term. In the present study, we used transiliac bone biopsy samples and assessed the intrinsic material properties of the bone tissue at the micron-level by combined backscattered electron imaging and nanoindentation. Paired iliac bone samples from 14 patients (age 3 to 17 years) with severe OI before and after 2.5 +/- 0.5 years (mean +/- SD) of pamidronate treatment as well as age-matched controls were examined. Bone histomorphometry was performed in all samples and confirmed an increase of bone mass in treated patients. Backscattered electron imaging was used to measure the weighted mean calcium content (Ca(Mean)), the most frequent calcium content (Ca(Peak)), the variation in mineralization (Ca(Width)) and the amount of lowly mineralized areas (Ca(Low)) that correspond to sites of primary mineralization. Nanoindentation was performed in a subgroup of 6 patients and 6 controls to determine hardness and elastic modulus. Compared to controls, untreated OI patients had a significantly higher degree of bone matrix mineralization (Ca(Peak) +7%, P < 0.001) and a strong reduction of Ca(Low) (-38%, P < 0.001) despite enhanced bone formation, as well as increased hardness (+21%, P < 0.01) and elastic modulus (+13%, P < 0.01). However, none of these parameters was significantly altered by the subsequent pamidronate treatment. This shows that OI bone is stiffer and more mineralized and that, despite the enhanced bone formation rate in these patients, areas of primary mineralization are hardly visible. We also conclude that pamidronate treatment in children with OI does not have an adverse effect on the intrinsic material properties of bone and, as a consequence, that a long-term administration of the drug might not increase brittleness and fragility of the bone matrix. The antifracture effectiveness of pamidronate treatment in OI, as shown in previous clinical studies, has to be explained by the increase of mainly cortical bone volume.

Adolescent↗
PubMed2006

Observation of entanglement of a single photon with a trapped atom.

We report the observation of entanglement between a single trapped atom and a single photon at a wavelength suitable for low-loss communication over large distances, thereby achieving a crucial step towards long range quantum networks. To verify the entanglement, we introduce a single atom state analysis. This technique is used for full state tomography of the atom-photon qubit pair. The detection efficiency and the entanglement fidelity are high enough to allow in a next step the generation of entangled atoms at large distances, ready for a final loophole-free Bell experiment.

Journal Article↗
PubMed2006

Time trends in the epidemiology of renal transplant patients with type 1 diabetes mellitus over the last four decades.

BACKGROUND: Diabetes mellitus (DM) type 1 is an important contributor to end-stage renal disease (ESRD) among younger transplant recipients. However, little is known about the changes in epidemiological characteristics of this population. Especially, time to reach ESRD may have changed in type 1 diabetic patients referred for transplantation, resulting in higher age at time of grafting. Such time trends may allow anticipating future developments regarding the demand for organ replacement in this patient group. METHODS: We retrospectively analysed 173 patients with type 1 DM undergoing renal transplantation at our institution, stratified into four groups according to year of reaching ESRD (A = 1973-1983, B = 1984-1990, C = 1991-1995 and D = 1996-2002). For each group we determined age at diagnosis of DM, age at time of reaching ESRD and age at time of transplantation. From these data, the interval from diagnosis of DM to ESRD and from ESRD to transplantation was calculated. The results were analysed in relation to gender, year of and age at onset of diabetes. RESULTS: Patients reaching ESRD in more recent years (group D) tended to be both younger at diagnosis of DM and older when reaching ESRD, resulting in higher mean age at transplantation (35.0, 37.5, 39.6 and 41.0 years in groups A, B, C and D, respectively). Accordingly, median duration to ESRD has significantly been prolonged over the last five decades in patients with type 1 DM undergoing renal transplantation (group A: 21.0, B: 20.7, C: 22.3 and D: 28.5 years; P < 0.0001), this finding being more pronounced in female patients. CONCLUSIONS: The results of our analysis are compatible with a change in epidemiology in patients undergoing kidney transplantation. Older age at time of reaching ESRD may impact significantly on the demand for renal grafts, as patients are already clearly older nowadays when being transplanted. From our data it cannot be concluded whether this development is due to a change in the progression of diabetic nephropathy or may simply reflect a change in the selection of type 1 diabetic patients referred for transplantation.

Adolescent↗
PubMed2006

[Benefits and risks of bariatric surgery].

The rapid increase of morbid obesity has become an important task in the Western world in recent years. Since conservative treatments have failed to prove sufficient efficacy, surgery has turned out to be the most powerful option in treating morbid obesity. In this paper, the different surgical techniques with their advantages and drawbacks are presented. In general, there are restrictive, malabsorptive and combinations of both procedures available. The adjustable gastric banding (Figure 1) represents a purely restrictive operation. It is useful for patients with a relatively low body mass index (BMI) and a good understanding and control of their eating habits. By contrast, the duodenal switch (Figure 2) stands for a mainly malabsorptive procedure that might be indicated in patients with a very high BMI. The Roux-en-Y gastric bypass (Figure 3) is the most widely used bariatric procedure worldwide. It combines restriction and malabsorption. Today, almost two thirds of all bariatric procedures are performed laparoscopically, which has further enhanced the use of surgery in the treatment of morbid obesity. In conclusion, the treatment of morbid obesity represents a significant challenge in the Western world, and bariatric surgery plays a paramount role in the fight against overweight.

Bariatric Surgery↗
PubMed2006

Physical and psychosocial outcome in morbidly obese patients with and without bariatric surgery: a 4 1/2-year follow-up.

BACKGROUND: Morbidly obese patients show high somatic and psychiatric co-morbidity. Bariatric surgery is accepted as the obesity treatment with the greatest long-term success. There is growing evidence that follow-up studies should address somatic as well as psychosocial conditions of patients undergoing bariatric surgery and non-operatively treated patients. This study investigates the physical and psychosocial outcomes of patients with and without bariatric surgery. METHODS: A sample of 131 morbidly obese patients applying for bariatric surgery underwent somatic and psychological assessment (T0). A first follow-up study (T1) was conducted 2 years after T0 in 119 patients. The present second follow-up (T2) was carried out 4 1/2 years after T0 and 3.2 years after potential bariatric surgery. Psychological/psychosocial measures were collected in the 93 patients, 63 of whom were treated surgically, via the Psychosocial Stress and Symptom Questionnaire (PSSQ) and a telephone interview covering BMI, employability, medication, doctor consultations, eating behavior, and physical/psychological well-being. RESULTS: Patients with and without bariatric surgery showed a BMI reduction, which was significantly greater in those who underwent surgery (P<.001). The average percentage of excess weight loss (%EWL) between T0 and T2 was 11.5% in patients with no bariatric surgery, 36.0% in patients with laparoscopic gastric banding, and 52.8% in patients with laparoscopic gastric bypass (%EWL between T0 and T2 in patients of all groups significant, P<.001). Patients with and without surgical treatment showed significant improvement with regard to depressive symptoms and binge-eating behavior. Three-quarters of the surgically-treated and two-thirds of the non-treated patients rated their physical, psychological, and psychosocial well-being as "good" at T2. CONCLUSION: After 3 to 4 years, all of the patients have adapted well to their weight and body appearance, regardless of whether they have undergone surgery. Weight loss is, however, greater for operated patients, which strongly decreases the risk of developing obesity-related co-morbidities.

Adult↗
PubMed2006

Perforated ulcer at the gastrojejunostomy: laparoscopic repair after Roux-en-Y gastric bypass.

A 44-year-old woman was admitted from the emergency department with severe acute upper abdominal pain. The patient had undergone a laparoscopic Roux-en-Y gastric bypass (RYGBP) operation 16 months previously. CT scan showed intraabdominal free air. At emergency laparoscopic reoperation, a perforated ulcer at the gastrojejunostomy was found. This late complication of RYGBP can be a rapidly progressing life-threatening situation, and requires prompt treatment. Closure and omental patch were successful laparoscopically.

Adult↗
PubMed2006

New device for the introduction of a circular stapler in laparoscopic gastric bypass surgery.

BACKGROUND: In laparoscopic Roux-en-Y gastric bypass (LRYGBP) surgery, the anastomosis between the gastric pouch and the jejunum can be performed using a circular stapler, as described in the original publication by Wittgrove in 1994. The introduction of the circular stapler through the thick abdominal wall in morbidly obese patients can be challenging. To overcome the difficulties of this task, a new device was developed and its use is presented. METHOD: The new device has the shape of a trocar tip which can be mounted on the circular stapler, giving it the properties of a trocar. Therefore, easier introduction into the abdominal cavity is feasible. The use of the device was assessed analyzing the data of a prospective database, comparing patient groups operated without the device (n=301) and patients operated with the device (n=100). RESULTS: The groups were comparable in age, sex, BMI and number of previous abdominal operations. The wound infection rate at the site of stapler introduction decreased from 6.6% to 1% (P=0.035). The overall operating time, hospital stay and complication rate were unchanged. CONCLUSION: The new device proved to be useful in daily practice and enabled an easier stapler introduction with fewer wound infections.

Adult↗
PubMed2005

Transplantation of infant en bloc kidneys into paediatric recipients.

En bloc renal transplantation (EBT) from infant donors is an option for children with end-stage renal failure. Owing to potential complications, EBT is not performed in all paediatric nephrology centres. We evaluated the perioperative and long-term course of five children undergoing EBT. Primary diagnosis was atypical (diarrhoea-negative) haemolytic uraemic syndrome (n=2), interstitial nephropathy (two siblings) and branchio-oto-renal syndrome (n=1). Recipient and donor ages ranged between 5.9 and 11.1 years and 0.3 and 2.5 years, respectively. Follow-up time after EBT was 2.1-13.2 years. Perioperative complications included (1) a renal artery thrombosis, with immediate intraoperative reconstruction and primary non-functioning of the graft, with recovery after 10 days, and (2) a vesico-ureteric obstruction, successfully managed with temporary insertion of a JJ-catheter. All grafts had good long-term function. Absolute glomerular filtration rate (GFR; millilitres/minute) increased in all patients, whereas relative GFR (millilitres/minute per 1.73 m(2) body surface area) remained stable during the follow-up period in all but one. Kidney size increased significantly, with maximal growth during the first year after EBT; magnetic resonance imaging (MRI) showed normal structure and vasculature. EBT is a safe and effective option for young children with end-stage renal failure. Absolute GFR and graft size increase and adapt to the children's growing body mass.

Age Factors↗
PubMed2005

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.

Adrenal Cortex Hormones↗
PubMed2005

Abdominal compartment syndrome after liver transplantation.

The abdominal compartment syndrome is a well-known complication after abdominal trauma and is increasingly recognized as a potential risk factor for renal failure and mortality after adult orthotopic liver transplantation (OLT). We present a case report of a young patient who presented with acute liver failure complicated by an acute pancreatitis. The patient developed an acute abdominal compartment syndrome after OLT. Transurethral measurement of intraabdominal pressure indicated an abdominal compartment syndrome associated with impaired abdominal vascular perfusion, including liver perfusion. Renal insufficiency was immediately reversed after decompressive bedside laparotomy. The abdominal compartment syndrome is a potential source of posttransplant renal insufficiency and liver necrosis in OLT. It remains, however, a rarely described complication after liver transplantation, despite the presence of significant factors that contribute to elevated intraabdominal pressure.

Adult↗
PubMed2005

Neurophysiological measures in amyotrophic lateral sclerosis: markers of progression in clinical trials.

In this review we evaluate clinical neurophysiological methods, originally described for use in diagnosis that can be applied to measurement of change during the progress of amyotrophic lateral sclerosis (ALS). Such measurements are potentially important in clinical trials, and also in clinical practice. We have assessed methods for lower and upper motor neuron function, including conventional EMG, nerve conduction and F-wave studies, the derived Neurophysiological Index, motor unit counting methods (MUNE), and transcranial magnetic motor cortex stimulation. We have also addressed the validity of measurements of electromechanical coupling. Methods for measuring muscle strength are beyond the scope of this review. We conclude that MUNE, M-wave amplitude and the Neurophysiological Index are sufficiently reliable, sensitive, and relevant to the clinical problem of ALS, to be used in clinical trials in the disease. Transcranial magnetic stimulation is of limited value, but a combination of the measurements made as part of this technique may also be useful. We conclude that clinical neurophysiological techniques should now be used in measuring change in clinical trials in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Laparoscopic pouch resizing and redo of gastro-jejunal anastomosis for pouch dilatation following gastric bypass.

BACKGROUND: With a dramatically increasing number of bariatric operations performed world-wide in the recent years, more late complications have been noticed. Proximal gastric pouch dilatation is a known late complication after laparoscopic or open restrictive surgery for morbid obesity. In the present paper, we report our experience with laparoscopic re-operation of enlarged gastric pouches after laparoscopic gastric bypass, with emphasis on technique and outcome. METHODS: Data were retrieved from a prospective database of 334 patients who underwent a laparoscopic gastric bypass operation at the University Hospital of Zurich from July 2000 to December 2004. Five laparoscopic revisions for pouch dilatation after primary bypass were performed. RESULTS: 3 female and 2 male patients with median age 40 years (range 32-55) underwent a laparoscopic pouch resizing. At the time of the re-operation, the median BMI was 32.0 kg/m(2) (range 28.4-48.4). All procedures were performed laparoscopically with no conversion to open surgery. The median operating-time was 110 minutes (95-120). The median hospital stay was 6 days (range 5-14). The median BMI in the follow-up of 12 months (9-14) was 28.0 kg/m(2) (25.5-45.8). Diabetes mellitus improved in 4 cases during follow-up. CONCLUSION: Laparoscopic pouch resizing with redo of the gastro-jejunal anastomosis was feasible, safe and effective in this small series. It led to further weight loss and improved symptoms of poor pouch emptying.

Adult↗
PubMed2005

Central necrosis in isolated hypoxic human pancreatic islets: evidence for postisolation ischemia.

A variety of explanations have been provided to elucidate the requirement of the large islet mass that is essential for a successful treatment of patients with type I diabetes by intrahepatic transplantation. The purpose of this study was to investigate islet cell survival under the effect of prolonged hypoxia and/or nutrient withdrawal, which mimics posttransplantation environment of transplanted islets in the liver. We studied the influence of 24 h of hypoxia (1% O2) in intact isolated human and rat islets as well as the effect of combined oxygen/nutrient deprivation in a mouse insulinoma cell line (MIN6). In intact human islets, 24 h of hypoxia led to central necrosis combined with apoptotic features such as nuclear pyknosis and DNA fragmentation. In the course of hypoxic treatment, ultrastructural analysis demonstrated a gradual transition from an apoptotic to a necrotic morphology particularly pronounced in central areas of large islets. In MIN6 cells, on the other hand, hypoxia led to a twofold (p < 0.01) increase in caspase-3 activity, an indicator of apoptosis, but not to necrosis, as determined by release of lactate dehydrogenase (LDH). Only in combination with nutrient/serum deprivation was a marked increase in LDH release observed (sixfold vs. control, p < 0.01). We therefore conclude that, similar to MIN6 cells, central necrosis in isolated hypoxic islets is the result of the combined effects of hypoxia and nutrient/serum deprivation, most likely due to limited diffusion. Provided that transplanted islets undergo a similar fate as shown in our in vitro study, future emphasis will require the development of strategies that protect the islet graft from early cell death and accelerate the revascularization process.

Adenosine Triphosphate↗
PubMed2004

Psychosocial impact of living-related kidney transplantation on donors and partners.

Living-related kidney transplantation (LRKT) is an option for children with end-stage renal failure. In addition to medical concerns, there is uncertainty about the psychological impact of living-related donation on parent donors and families. A survey was conducted on the decision making process and medical and psychosocial consequences of LRKT. Between 1992 and 1999, 20 parents donated a kidney for their child. A questionnaire including 24 items was sent to parent donors and their partners. Nineteen parents and partners responded; the median time after LRKT was 3 years. Donors and partners reported an independent decision making process with no significant influence of partners, relatives, or hospital staff. Partners were more concerned about medical problems than donors themselves (P <0.02). Donors and partners cited no medical problems except sustained pain. Both reported an improved personal relationship towards the transplanted child. Donors and partners also cited an improved personal relationship. The vast majority (18/19) of couples still supported the decision for organ donation. In conclusion, there was a high degree of satisfaction with the decision making process in LRKT. The great majority of donors and partners did not report negative medical or psychological consequences. The relationship between donor, partner, and recipient child improved after LRKT.

Adolescent↗