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Markus Weber

Publications and source records attributed to Markus Weber.

At least 37 records · Page 2Linked to original sources
PubMed2004

HIV-specific cellular immune response is inversely correlated with disease progression as defined by decline of CD4+ T cells in relation to HIV RNA load.

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is approximately 8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4(+) T cell responses and, to a lesser extent, HIV-specific CD8(+) T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progression.

Adult↗
PubMed2004

HIV-1 does not provoke alteration of cytokine gene expression in lymphoid tissue after acute infection ex vivo.

The cytokine response to invading microorganisms is critical for priming the adaptive immune response. During acute HIV infection, the response is disrupted, but the mechanism is poorly understood. We examined the cytokine response in human lymphoid tissue, acutely infected ex vivo with HIV. Lymphoid tissue was cultured either as blocks or as human lymphocyte aggregate cultures (HLAC) of tonsils and lymph nodes. This approach allowed us to examine the effects of HIV on cytokines using distinct culture techniques. In contrast to HLAC, mock-infected tissue blocks displayed a 50- to 100-fold up-regulation of mRNAs for IL-1beta, -6, and -8 in the first 6 days of culture. Parallel increases were also noted at the protein level in the supernatants. Although IL-1beta, -6, and -8 are known to synergistically enhance HIV replication, peak HIV replication (measured as p24 Ag) was similar in tissue blocks and HLAC. Surprisingly, vigorous HIV replication of CXCR4- and CCR5-tropic HIV strains did not result in characteristic mRNA profiles for IL-1beta, -2, -4, -6, -8, -10, -12, -15, IFN-gamma, TNF-alpha, TGF-beta, and beta-chemokines in tissue blocks or HLAC. The increased expression of IL-1beta, -6, and -8 in tissue blocks may approximate clinical situations with heightened immune activation; neutralization of these cytokines resulted in inhibition of HIV replication, suggesting that these cytokines may contribute to HIV replication in certain clinical settings. These results also indicate that different molecular mechanisms govern HIV replication in tissue blocks and HLAC. Prevention of effective cytokine responses may be an important mechanism that HIV uses during acute infection.

Adolescent↗
PubMed2004

Visualization of transport: NMR microscopy experiments with model objects for porous media with pore sizes down to 50 microm.

Hydrodynamic flow and electric currents through model porous media were investigated. The transport rates through the individual pathways of the pore network are determined by the local width of the pore channels and by the driving mechanism. The model objects represent quasi two-dimensional random site percolation clusters. The calculated design was realized by milling the structure in polystyrene sheets. Velocity maps of stationary flow and current density maps of stationary currents through the cluster were acquired by magnetic resonance imaging methods. The findings were compared to the results of numerical simulations based on the same structure. Since the difference in the transport patterns of the different driving mechanisms are expected to be more pronounced in smaller pore spaces, ultra deep X-ray lithography has been used for the fabrication of downsized model objects with a spatial resolution of better than 50 microm and an aspect ratio as large as 20. First results obtained with these objects are reported.

Computer Simulation↗
PubMed2004

Laparoscopic gastric bypass is superior to laparoscopic gastric banding for treatment of morbid obesity.

OBJECTIVE: To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity. SUMMARY BACKGROUND DATA: Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy. METHODS: Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender. RESULTS: Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities. CONCLUSIONS: Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.

Adult↗
PubMed2004

Successful simultaneous islet-kidney transplantation using a steroid-free immunosuppression: two-year follow-up.

We report on the feasibility of a glucocorticoid-free immunosuppression (sirolimus, low-dose tacrolimus, and daclizumab) in simultaneous islet-kidney transplantation in nine patients with type 1 diabetes. There was one renal primary nonfunction. Renal function (n = 8) as assessed by creatinine and creatinine clearance over time was 103 +/- 6 micromol/L and 64 +/- 6 mL/min/1.73 m(2), respectively. Five out of six patients with >or= 2 islet transplantations became insulin independent. The mean HbA(1c) during the follow-up period for all patients after transplantation is 6.2 +/- 0.9% as compared with 8.7 +/- 1.9% prior to transplant. These results in patients with a median follow-up of 2.3 years suggest that kidney transplantation under a glucocorticoid-free immunosuppression is feasible, and that the rate of insulin independence of 80% can be achieved not only in patients with no or minimal diabetes complications, but also in patients with more advanced late complications and in conjunction with kidney transplantation.

Adult↗
PubMed2004

CpG oligodeoxynucleotides block human immunodeficiency virus type 1 replication in human lymphoid tissue infected ex vivo.

Oligodeoxynucleotides (ODNs) with immunomodulatory motifs control a number of microbial infections in animal models, presumably by acting through toll-like receptor 9 (TLR9) to induce a number of cytokines (e.g., alpha interferon and tumor necrosis factor alpha). The immunomodulatory motif consists of unmethylated sequences of cytosine and guanosine (CpG motif). ODNs without CpG motifs do not trigger TLR9. We hypothesized that triggering of TLR9 generates a cellular environment unfavorable for human immunodeficiency virus (HIV) replication. We tested this hypothesis in human lymphocyte cultures and found that phosphorothioate-modified ODN CpG2006 (type B ODNs) inhibited HIV replication nearly completely and prevented the loss of CD4(+) T cells. ODNs CpG2216 and CpG10 (type A ODNs) were less effective. CpG2006 blocked HIV replication in purified CD4(+) T cells and T-cell lines; CpG10 was ineffective in this setting, indicating that type A ODNs may inhibit HIV replication in CD4(+) T-cell lines indirectly through a separate cell subset. However, control ODNs without CpG motifs also showed anti-HIV effects, indicating that these effects are nonspecific and not due to TLR9 triggering. The mechanism of action is not clear. CpG2006 and its control ODN blocked syncytium formation in a cell fusion-based assay, but CpG10, CpG2216, and their control ODNs did not. The latter types interfered with the HIV replication cycle during disassembly or reverse transcription. In contrast, CpG2006 and CpG2216 specifically induced cytokines critical to initiation of the innate immune response. In summary, the nonspecific anti-HIV activity of CpG ODNs, their ability to stimulate HIV replication in latently infected cells, potentially resulting in their elimination, and their documented ability to link the innate and adaptive immune responses make them attractive candidates for further study as anti-HIV drugs.

Adjuvants, Immunologic↗
PubMed2003

Obesity in general elective surgery.

BACKGROUND: Obese patients are generally believed to be at a higher risk for surgery than those who are not obese, although convincing data are lacking. METHODS: We prospectively investigated a cohort of 6336 patients undergoing general elective surgery at our institution to assess whether obesity affects the outcome of surgery. Exclusion criteria were emergency, vascular, thoracic, and bariatric operations; transplantation procedures; patients under immunosuppression; and operations done under local anaesthesia. Postoperative morbidity was analysed for non-obese and obese patients (body-mass index <30 kg/m(2) vs >or=30 kg/m(2)). Obesity was further stratified into mild obesity (30.0-34.9 kg/m(2)) and severe obesity (>or=35 kg/m(2)). Risk factors were analysed with univariate and multivariate models. FINDINGS: The cohort consisted of 6336 patients, of whom 808 (13%) were obese, 569 (9%) were mildly obese, and 239 (4%) had severe obesity. The morbidity rates in patients who were obese compared with those who were not were much the same (122 [15.1%] of 808 vs 901 [16.3%] of 5528; p=0.26), with the exception of an increased incidence of wound infections after open surgery in patients who were obese (17 [4%] of 431 vs 92 [3%] of 3555, p=0.03). Incidence of complications did not differ between patients who were mildly obese (91 [16.0%] of 569), severely obese (36 [15.1%] of 239), and non-obese (901 [16.3%] of 5528; p=0.19). In multivariate regression analyses, obesity was not a risk factor for development of postoperative complications. Of note, the additional medical resource use as estimated by a new classification of complications showed no differences between patients who were and were not obese. INTERPRETATION: Obesity alone is not a risk factor for postoperative complications. The regressive attitude towards general surgery in obese patients is no longer justified.

Adult↗
PubMed2003

Ascertaining the values of sigma x, sigma y, and sigma z of a polarization qubit.

In the 1987 spin-retrodiction puzzle of Vaidman, Aharonov, and Albert one is challenged to ascertain the values of sigma(x), sigma(y), and sigma(z) of a spin-1/2 particle by utilizing entanglement. We report the experimental realization of a quantum-optical version in which the outcome of an intermediate polarization projection is inferred by exploiting single-photon two-qubit quantum gates. The experimental success probability is consistently above the 90.2% threshold of the optimal one-qubit strategy, with an average success probability of 95.6%.

Journal Article↗
PubMed2003

Laparoscopic Roux-en-Y gastric bypass, but not rebanding, should be proposed as rescue procedure for patients with failed laparoscopic gastric banding.

OBJECTIVE: To define whether laparoscopic rebanding or Roux-en-Y gastric bypass represents the best approach for failed laparoscopic gastric banding in patients with morbid obesity. SUMMARY BACKGROUND DATA: Countless laparoscopic gastric bandings have been implanted during the recent years worldwide. Despite excellent short-term results, long-term failures and complications have been reported in more than 20% of patients. Which rescue procedures should be used remains controversial. Therefore, we analyzed our experience with the use of laparoscopic rebanding versus laparoscopic Roux-en-Y gastric bypass after failed gastric banding. METHODS: Using a prospectively collected database, we analyzed the feasibility, safety, and effectiveness of laparoscopic rebanding versus laparoscopic conversion to Roux-en-Y gastric bypass after failed laparoscopic gastric banding. RESULTS A total of 62 consecutive patients were treated in our institution between May 1995 and December 2002 for failed primary laparoscopic gastric banding, including 30 laparoscopic rebandings and 32 laparoscopic conversions to Roux-en-Y gastric bypass. Rebandings were preferably done during the initial period of the study and Roux-en-Y gastric bypass in the last period. Both groups were comparable before the initial banding procedures. At the time of redo surgery, patients receiving a gastric bypass had more esophageal dysmotility (47% vs. 7%, P = 0.002) and higher body mass index (BMI) than those elected for rebanding procedures (BMI 42.0 vs. 38.4 kg/m2, P = 0.015). Feasibility and safety: Each procedure was performed laparoscopically. Mean operating time was 215 minutes for gastric bypass and 173 minutes for rebanding (P = 0.03). Early complications occurred in one case in the rebanding group and in 2 cases in the bypass group; all underwent a laparoscopic reexploration without the need for open surgery. There was no mortality in this series. Effectiveness: BMI in the gastric bypass group decreased from 42.0 to 31.8 kg/m2 (P = 0.02) within 1 year of surgery, while it remained unchanged in the rebanding group. CONCLUSIONS: Laparoscopic conversion to a gastric bypass as well as laparoscopic rebanding are feasible and safe. Conversion to gastric bypass offers a significant advantage in terms of further weight loss after surgery. Therefore, this procedure should be considered as the rescue therapy of choice after a failed laparoscopic gastric banding.

Adult↗
PubMed2002

Rayleigh-Bénard percolation transition of thermal convection in porous media: computational fluid dynamics, NMR velocity mapping, NMR temperature mapping.

Stationary thermal convection and heat conduction were studied in random-site percolation clusters in a Rayleigh-Bénard configuration experimentally by NMR microscopy techniques and numerically with the aid of a finite volume method. The porosity of the percolation clusters, and the temperature difference applied to the convection cell were varied. Two-dimensional percolation networks were generated with the aid of a random-number algorithm. The resulting clusters were used as templates for the fabrication of model objects. The convective velocity distribution of silicon oil or ethylene glycol filled into the pore space was mapped and evaluated in the form of histograms. The flow patterns visualized in the simulated and the measured velocity maps show good coincidence. In the histograms, two velocity regimes can be distinguished and attributed to local convection rolls responsible for the low-velocity part, and cluster-spanning flow loops characterized by a high-velocity cut-off, respectively. The maximum velocity as a function of the porosity and the overall temperature difference is shown to be indicative for the hydro-thermodynamic Rayleigh-Bénard instability and the geometrical percolation threshold. The coincidence of the Rayleigh-Bénard instability (modified for porous media) and the percolation transition (modified for closed loops) gives rise to a new critical phenomenon termed the Rayleigh-Bénard percolation transition. It occurs at a certain combination of the porosity and the overall temperature difference in the cell. Temperature maps were recorded with the aid of a relaxation-based NMR technique. The consequence of different thermal conductivities in the matrix and in the fluid is that horizontal-temperature gradients arise even in the absence of flow. This leads to a superposition of uncritical convective flow driven by the horizontal-temperature gradients whenever closed-loop pathways are possible and the critical Rayleigh-Bénard convection based on vertical-temperature gradients.

Journal Article↗
PubMed2002

Maps of electric current density and hydrodynamic flow in porous media: NMR experiments and numerical simulations.

The electric current density in percolation clusters was mapped with the aid of a NMR microscopy technique monitoring the spatial distribution of spin precession phase shifts caused by the currents. A test structure and a quasi-two-dimensional random-site percolation model object filled with an electrolyte solution were examined and compared with numerical simulations based on potential theory. The current density maps permit the evaluation of histograms and of volume-averaged current densities as a function of the probe volume radius as relationships characterizing transport in the clusters. The current density maps are juxtaposed to velocity maps acquired in flow NMR experiments in the same objects. It is demonstrated that electric current and hydrodynamic flow lead to transport patterns deviating in a characteristic way due to the different dependencies of the transport resistances on the pore channel width.

Journal Article↗
PubMed2002

Kidney transplantation from donors without a heartbeat.

BACKGROUND: The dramatic shortage of kidney donors has triggered interest in other sources of organs, such as donors without a heartbeat. Accumulating evidence suggests that the short-term survival of cadaveric kidneys from such donors is similar to that of cadaveric kidneys from donors with a heartbeat. However, no data from large, matched studies with long-term follow-up are available. We conducted a matched, single-center study of kidney transplants obtained from donors without a heartbeat and those from donors with a heartbeat, with a 15-year follow-up period. METHODS: Between 1985 and 2000, 122 kidney transplantations involving donors without a heartbeat were performed at the University of Zurich, in Switzerland. Outcomes of these procedures were compared with those of 122 transplantations of kidneys from donors with a heartbeat. The recipients were matched according to age, sex, number of transplantations, and calendar period of transplantation. RESULTS: The characteristics of the recipients did not differ significantly between the two groups. We observed a significantly higher incidence of delayed graft function among the patients who received kidneys from donors without a heartbeat (48.4 percent) than among the patients who received kidneys from donors with a heartbeat (23.8 percent) (P<0.001). However, the long-term rate of graft survival was similar in the two groups (P=0.98): at 10 years, the rate of graft survival was 78.7 percent for kidneys from donors without a heartbeat and 76.7 percent for kidneys from donors with a heartbeat. CONCLUSIONS: Although the incidence of delayed graft function is significantly higher with kidneys from donors without a heartbeat than with kidneys from donors with a heartbeat, there is no difference in long-term outcome between the two types of graft.

Adult↗
PubMed2002

Apoptosis in hypoxic human pancreatic islets correlates with HIF-1alpha expression.

To become insulin independent, patients with type 1 diabetes mellitus require transplantation of at least two donor pancreata because of massive beta-cell loss in the early post-transplantation period. Many studies describing the introduction of new immunosuppressive protocols have shown that this loss is due to not only immunological events but also nonimmunological factors. To test to what extent hypoxia may contribute to early graft loss, we analyzed the occurrence of apoptotic events and the expression of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-dependent alpha subunit and a constitutive beta subunit. Histological analysis of human and rat islets revealed nuclear pyknosis as early as 6 h after hypoxic exposure (1% O2). Moreover, immunoreactivity to activated caspase-3 was observed in the core region of isolated human islets. Of note, both of these markers of apoptosis topographically overlap with HIF-1alpha immunoreactivity. HIF-1alpha mRNA was detected in islets from human and rat as well as in several murine beta-cell lines. When exposed to hypoxia, mouse insulinoma cells (MIN6) had an increased HIF-1alpha protein level, whereas its mRNA level did not alter. In conclusion, our data provide convincing evidence that reduced oxygenation is an important cause of beta-cell loss and suggest that HIF-1alpha protein level is an indicator for hypoxic regions undergoing apoptotic cell death. These observations suggest that gene expression under the control of HIF-1 represents a potential therapeutic tool for improving engraftment of transplanted islets.

Active Transport, Cell Nucleus↗
PubMed2002

Magnetic stimulation of the central and peripheral nervous systems.

Since 1985, when the technique of transcranial magnetic stimulation (TMS) was first developed, a wide range of applications in healthy and diseased subjects has been described. Comprehension of the physiological basis of motor control and cortical function has been improved. Modifications of the basic technique of measuring central motor conduction time (CMCT) have included measurement of the cortical silent period, paired stimulation in a conditioning test paradigm, repetitive transcranial magnetic stimulation (rTMS), and peristimulus time histograms (PSTH). These methods allow dissection of central motor excitatory versus inhibitory interplay on the cortical motor neuron and its presynaptic connections at the spinal cord, and have proven to be powerful investigational techniques. TMS can be used to assess upper and lower motor neuron dysfunction, monitor the effects of many pharmacological agents, predict stroke outcome, document the plasticity of the motor system, and assess its maturation and the effects of aging, as well as perform intraoperative monitoring. The recent use of rTMS in the treatment of depression and movement disorders is novel, and opens the way for other potential therapeutic applications.

Central Nervous System↗