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Biomedical subjects

M Pfeiffer

Publications and source records attributed to M Pfeiffer.

At least 19 recordsLinked to original sources

[A postoperative infectious complication in a patient with rheumatoid arthritis treated with adalimumab].

Tumor necrosis factor (TNF) blocking agents, such as adalimumab, are well tolerated and provide improvement in the symptoms and signs of rheumatoid arthritis (RA). Due to its immunosuppressive effect, an increased risk of infection has been suggested, but so far no differences between adalimumab and placebo groups have been found in pivotal trials. Patients with RA succumb to postoperative complications because they have a systemic disease and use medication with immunosuppressive effects. We report on a patient with longstanding, active RA who had received adalimumab 40 mg every other week with prolonged infection, wound dehiscence and pseudoarthrosis following reconstructive forefoot surgery due to deformities secondary to RA. The postoperative infection occurred although adalimumab therapy had been stopped 8 days before surgery. The half-life of adalimumab is 10.0-13.6 days following a single intravenous dose. Whether patients under therapy with adalimumab are at an increased risk of developing postoperative complications is unclear, a retrospective analysis of the pivotal studies would be helpful in estimating the risk of perioperative (wound) infections in patients receiving anti-TNF. Moreover, it is not clear when therapy should be stopped prior to surgical intervention. Obviously prospective clinical trials would be more convincing.

Adalimumab↗

Determination of residual T- and B-cell content after immunomagnetic depletion: proposal for flow cytometric analysis and results from 103 separations.

BACKGROUND: T- and B-cell depletion of apheresis products is an attractive alternative to standard stem cell enrichment in haplo-identical transplantation. Thorough T- and B-cell depletion is necessary for prevention of acute GvHD and T-cell depletion-associated lymphoproliferative disorders. However, the large number of non-T and -B cells in the graft requires special protocols for the determination of extremely low frequencies of residual T cells. METHODS: Apheresis products from healthy donors were T- and B-cell depleted by the CliniMACS system using CD3 and CD19 Ab reagents and the LS tubing set. The recovery of cells and degree of depletion were determined. A four-color multigating strategy was used for enumeration of residual T and B cells. RESULTS: One-hundred and three separations were performed, with a mean cell recovery of 38+/-12%, CD34 recovery of 61+/-16% and CD56 recovery of 63+/-33%. T and B cells were depleted by log 4.15+/-0.46 and log 3.64+/-0.63, respectively. Four-color multigating flow cytometry allowed the detection of single T cells. DISCUSSION: Combined T- and B-cell depletion is a feasible method for obtaining stem cell grafts with acceptable stem cell recovery, profound T- and B-cell depletion and a very high amount of NK cells and monocytes. However, analysis of residual T cells is challenging and requires special protocols.

Acute Disease↗

Observation of in-medium modifications of the omega meson.

The photoproduction of omega mesons on nuclei has been investigated using the Crystal Barrel/TAPS experiment at the ELSA tagged photon facility in Bonn. The aim is to study possible in-medium modifications of the omega meson via the reaction gamma + A --> omega + X --> pi(0)gamma + X('). Results obtained for Nb are compared to a reference measurement on a LH2 target. While for recoiling, long-lived mesons (pi(0), eta, and eta;(')), which decay outside of the nucleus, a difference in the line shape for the two data samples is not observed, we find a significant enhancement towards lower masses for omega mesons produced on the Nb target. For momenta less than 500 MeV/c an in-medium omega meson mass of M(medium) = [722(+4)(-4)(stat)+35-5(syst)] MeV/c(2) has been deduced at an estimated average nuclear density of 0.6rho(0).

Journal Article↗

Organic homojunction diodes with a high built-in potential: interpretation of the current-voltage characteristics by a generalized Einstein relation.

We realize p- and n-type doping of the organic semiconductor zinc-phthalocyanine using a novel strong organic donor. This allows us to demonstrate the first stable and reproducible organic p-n homojunctions. The diodes show very high built-in potentials, attractive, e.g., for organic solar cells. However, the diode characteristics cannot be described by the standard Shockley theory of the p-n junction since the ideality factor strongly increases with decreasing temperature. We show that this behavior can be explained by deviations from the Einstein relation for disordered materials.

Journal Article↗

Atmosphere-ocean dynamics in the Western Indian Ocean recorded in corals.

We present a set of Porites coral oxygen isotope records from the tropical and subtropical Western Indian Ocean covering the past 120-336 years. All records were thoroughly validated for proxy response to regional climate factors and their relation to large-scale climate modes. The records show markedly different imprints of regional climate factors. At the same time, all coral records show clear teleconnections between the Western Indian Ocean and the El Nino-Southern Oscillation (ENSO). The multi-proxy site analysis enables the detection of the covariance structure between individual records and climate modes such as ENSO. This method unravels shifts in ENSO teleconnectivity of the Western and Central Indian Ocean on multi-decadal time-scales (after 1976). The Seychelles record shows a stationary correlation with ENSO, Chagos corals show evidence for non-stationary delta18O/ENSO relationships and the Southwestern Indian Ocean corals show a strong relationship with ENSO when the forcing is strong (1880-1920, 1970 to present). Our results indicate that the coral delta18O, in combination with other proxies, can be used to monitor temporal and spatial variations in the sea-surface temperature and the fresh water balance within the Indian Ocean on interannual to interdecadal time-scales.

Animals↗

Thoracic herniation after lumbar spine fusion.

We report on a 65-year-old male patient with rapid onset of incomplete paraparesis, based on a massive thoracic herniation following adjacent instability of the thoracolumbar spine after lumbar fusions with transpedicular instrumentation.

Aged↗

Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation.

Relapse is a major problem after allogeneic transplantation in children with acute B-lineage lymphoblastic leukemias (ALL) and lymphomas and additional therapeutic strategies are needed to increase graft versus leukemia effects without inducing graft versus host disease (GvHD). Several studies have shown the efficacy of a humanized CD20 antibody (rituximab) for treatment of CD20+ malignancies together with conventional chemotherapy but less is known about its post transplant usefulness. We studied the ability of rituximab to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with effector cells and complement from patients who were transplanted with T-cell-depleted grafts from unrelated or mismatched related donors. Highest lytic activity (ADCC) was observed against leukemia-derived MHH4 cells and Burkitt's lymphoma-derived Raji cells in the first months after transplantation, corresponding to the high percentage of regenerating CD56+ CD16+ cells. Moreover, primary cryopreserved ALL-blasts from a pediatric patient were also efficiently lysed. Increased lysis was obtained after stimulation with interleukin-2. Combination of ADCC and CDC had additive effects. These findings encourage clinical trials on the use of rituximab for improving minimal residual disease control and relapse prevention after allogeneic high-risk transplantation in the small group of pediatric patients with CD20+ leukemias/lymphomas.

Animals↗

Photoproduction of eta-mesic 3He.

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma3He-->etaX has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV. A resonancelike structure just above the eta production threshold with an isotropic angular distribution suggests the existence of a resonant quasibound state. This is supported by studies of a competing decay channel of such a quasibound eta-mesic nucleus into pi(0)pX. A binding energy of (-4.4+/-4.2) MeV and a width of (25.6+/-6.1) MeV is deduced for the quasibound eta-mesic state in 3He.

Journal Article↗

The reaction gammap-->pi0gamma'p and the magnetic dipole moment of the Delta+ 1232 resonance.

The reaction gammap-->pi(0)gamma'p has been measured with the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI for energies between sqrt[s]=1221-1331 MeV. The cross section's differential in angle and energy have been determined for the photon gamma' in three bins of the excitation energy. This reaction channel provides access to the magnetic dipole moment of the Delta(+)(1232) resonance and, for the first time, a value of mu(Delta(+))=[2.7(+1.0)(-1.3)(stat)+/-1.5(syst)+/-3(theor)]mu(N) has been extracted.

Journal Article↗

In-medium modifications of the pipi interaction in photon-induced reactions.

Differential cross sections of the reactions (gamma,pi(0)pi(0)) and (gamma,pi(0)pi(+/-)) have been measured for several nuclei (1H,12C, and (nat)Pb) at an incident-photon energy of E(gamma)=400-460 MeV at the tagged-photon facility at MAMI-B using the TAPS spectrometer. A significant nuclear-mass dependence of the pipi invariant-mass distribution is found in the pi(0)pi(0) channel. This dependence is not observed in the pi(0)pi(+/-) channel and is consistent with an in-medium modification of the pipi interaction in the I=J=0 channel. The data are compared to pi-induced measurements and to calculations within a chiral-unitary approach.

Journal Article↗

Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children.

We present a clinical scale method for immunomagnetic separation of CD56+ donor natural killer cells for adoptive immunotherapy of pediatric leukemias after allogeneic transplantation. This time-saving and partially automated procedure employed CD56+ selection followed by CD3+ depletion, resulting in a median purity of 98.6% NK cells and a four-log depletion of T cells. The enriched NK cells demonstrated high cytotoxic activity against K562 target cells and fresh leukemic blasts with low HLA class I expression, which could be further enhanced by IL-2 stimulation. Lysis of NK-insensitive leukemic cells with high HLA class I expression could also be demonstrated via ADCC. Due to the high degree of T cell depletion, alloreactive proliferation in mixed lymphocyte cultures and response to T cell-specific mitogen stimulation was profoundly decreased. Our results suggest that, even in the case of mismatched donors, infusions of donor NK cells with extremely low T cell content may be a promising treatment option for leukemic minimal residual disease after allogeneic transplantation without risk of inducing severe GVHD.

CD56 Antigen↗

Systemic and local antibiotic prophylaxis in the prevention of prosthetic vascular graft infection: an experimental study.

AIM: to determine if local, in addition to systemic antibiotic prophylaxis (compared to that provided by systemic prophylaxis alone) provides additional benefit in terms of reducing graft infection. METHODS: gelatin-sealed Dacron grafts were interposed in the infrarenal aorta of 36 mongrels and inoculated with 1 ml of a S. aureus suspension. Group 1 (control group) received no prophylaxis and were inoculated with 1 ml containing 10(9)cfu/ml. Group 2 (n=6) received systemic prophylaxis (1 g cephamandole) and were inoculated with 10(5) cfu/ml (n=3) or 10(7) cfu/ml (n=3). Group 3 received systemic prophylaxis (1 g cephamandole) and were inoculated with 109 cfu/ml. Group 4 received systemic prophylaxis (2 g cephamandole) and were inoculated with 10(9)cfu/ml. In group 5 and 6 grafts were soaked in a rifampicin solution before use and inoculated with 10(9) cfu/ml. Group 5 received no systemic prophylaxis and group 6 received systemic prophylaxis (1 g cephamandole). Grafts were harvested at 2 weeks, and peritonitis, perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken of the graft, the perigraft tissues and the peritoneal fluid. Graft segments were incubated in broth medium. RESULTS: inoculation with 10(9) cfu/ml ensured graft infection. Systemic or local prophylaxis alone failed to prevent graft infection. Only systemic and local antibiotic prophylaxis provided significant better results than no prophylaxis at all (p<0.01) and local prophylaxis alone (p<0.05). However, total "graft sterility" was not achieved as bacteriologic analysis of the graft segments showed low bacterial counts (<10 bacteria/graft) in 5 of 6 grafts. CONCLUSION: local and systemic prophylaxis provided more protection as demonstrated by the significant decrease in the incidence of "overt" graft infection. Total "graft sterility" cannot be expected in the case of an overwhelming bacterial challenge.

Animals↗

[Spiroergometry in patients with severe chronic obstructive pulmonary disease confined to bed].

BACKGROUND: Exercise training is recommended for patients with severe chronic obstructive pulmonary disease (COPD) to improve the endurance capacity. While many patients confined to bed are not able to run exercise training, we investigated the influence of a bedside passive-ergometry on ventilation in patients with severe COPD. METHODS: In nine patients with severe COPD confined to bed (FEV1.0 0,94 +/- 0,18 l, IVC 2,3 +/- 0,8 l, Raw 0,91 +/- 0,13 kPa/l/s) we measured oxygen uptake O2, breathing frequency BF and minute ventilation E during rest, passive movement (30 revolutions per minute), additional active movement and maximal exercise. As a control group six healthy men were investigated during rest and passive movement. RESULTS: During maximal exercise in COPD patients O2 peak reached 618 +/- 177 ml/min, BF 26 +/- 7,2/min and E max 24,1 +/- 5 l/min. In rest O2 was 311 +/- 56 ml/min (53 % O2 peak), BF 17,6 +/- 3,1/min and E 13,3 +/- 2,7 ml/min (55 % E max), while during passive movement O2 was increased to 369 +/- 88 (62 % O2 peak), BF to 19 +/- 5,3 and E to 16,4 +/- 4,1 (68 % E max). In contrast O2 in control subjects dropped from 377,5 +/- 38 in rest to 336 +/- 27 ml/min during passive action, BF from 14 +/- 2,1 to 12 +/- 2,4/min and E from 11,1 +/- 1,3 to 9,1 +/- 1 ml/min. CONCLUSIONS: In patients with severe COPD oxygen uptake, breathing frequency and minute ventilation increased not only during active, but even during passive movement of a bedside ergometer. With this method an exercise training is possible even in COPD patients confined to bed.

Aged↗

Peripheral osteoid osteoma. Is there still a place for traditional surgery?

We treated 106 patients with a peripheral osteoid osteoma by conventional surgical methods; 81 had curettage and 25 en-bloc resection. The rate of local recurrence after curettage was 12% and after en-bloc resection 4.5%. Postoperative fractures were observed in 3% after curettage and in 4.5% after en-bloc resection. We compared our findings with those reported in the literature after minimally invasive treatment and concluded that curettage can be regarded as the treatment of choice in patients in whom minimally invasive methods do not offer any advantage, for example, for subperiosteal tumours which are readily accessible, or when the diagnosis is unclear and further histological analysis is required.

Adolescent↗

Direct observation of different surface structures on high-resolution images of native halorhodopsin.

Halorhodopsin (HR) was investigated with atomic force microscopic techniques (AFM) in aqueous solution. Two-dimensional (2D) crystals of HR were obtained by purifying an HR membrane fraction with the same buoyant density as the purple membrane (HR-PM) from the overexpressing strain Halobacterium salinarum D2. The membrane patches of HR were immobilized on mica. Images with a resolution up to 14 A were recorded. Crystals showed an orthogonal structure and the orientation of the molecules showed p42(1)2 symmetry; thus, alternate tetramers are inverted in the membrane. The crystal surface was found to display different structures depending on the imaging force used, indicating that some parts of the HR molecule are more rigid but others more compressible. From samples with single tetramers missing in the crystalline patches dimensions of the unit cell could be determined. Helix-connecting loops in single molecules of halorhodopsin were assigned. The images indicate that the large extracellular BC loop covers the whole molecule and is very flexible.

Aluminum Silicates↗

C-terminal splice variants of the mouse mu-opioid receptor differ in morphine-induced internalization and receptor resensitization.

The main analgesic effects of the opioid alkaloid morphine are mediated by the mu-opioid receptor. In contrast to endogenous opioid peptides, morphine activates the mu-opioid receptor without causing its rapid endocytosis. Recently, three novel C-terminal splice variants (MOR1C, MOR1D, and MOR1E) of the mouse mu-opioid receptor (MOR1) have been identified. In the present study, we show that these receptors differ substantially in their agonist-selective membrane trafficking. MOR1 and MOR1C stably expressed in human embryonic kidney 293 cells exhibited phosphorylation, internalization, and down-regulation in the presence of the opioid peptide [d-Ala(2),Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO) but not in response to morphine. In contrast, MOR1D and MOR1E exhibited robust phosphorylation, internalization, and down-regulation in response to both DAMGO and morphine. DAMGO elicited a similar desensitization (during an 8-h exposure) and resensitization (during a 50-min drug-free interval) of all four mu-receptor splice variants. After morphine treatment, however, MOR1 and MOR1C showed a faster desensitization and no resensitization as compared with MOR1D and MOR1E. These results strongly reinforce the hypothesis that receptor phosphorylation and internalization are required for opioid receptor reactivation thus counteracting agonist-induced desensitization. Our findings also suggest a mechanism by which cell- and tissue-specific C-terminal splicing of the mu-opioid receptor may significantly modulate the development of tolerance to the various effects of morphine.

Alternative Splicing↗

Dynamics of the proton transfer reaction on the cytoplasmic surface of bacteriorhodopsin.

The cytoplasmic surface of bacteriorhodopsin is characterized by a group of carboxylates that function as a proton attractive domain [Checover, S., Nachliel, E., Dencher, N. A., and Gutman, M. (1997) Biochemistry 36, 13919-13928]. To identify these carboxylates, we selectively mutated them into cysteine residues and monitored the effects of the dynamics of proton transfer between the bulk and the surface of the protein. The measurements were carried out without attachment of a pH-sensor to the cysteine residue, thus avoiding any structural perturbation and change in the surface charge caused by the attachment of a reporter group, and the protein was in its BR state. The purple membranes were suspended in an unbuffered solution of pyranine (8-hydroxypyrene-1,3,6-trisulfonate) and exposed to a train of 1000 laser pulses (2.1 mJ/pulse, lambda = 355 nm, at 10 Hz). The excitation of the dye ejected the hydroxyl's proton, and a few nanoseconds later, a pair of free protons and ground-state pyranine anion was formed. The experimental observation was the dynamics of the relaxation of the system to the prepulse state. The observed signals were reconstructed by a numeric method that replicates the chemical reactions proceeding in the perturbed space. The detailed reconstruction of the measured signal assigned the various proton-binding sites with rate constants for proton binding and proton exchange and the pK values. Comparison of the results obtained by the various mutants indicates that the dominant proton-binding cluster of the wild-type protein consists of D104, E161, and E234. The replacement of D104 or E161 with cysteine lowered the proton binding capacity of the cluster to approximately 60% of that of the native protein. The replacement of E234 with cysteine disrupted the structure of the cluster, causing the two remaining carboxylates to function as isolated residues that do not interact with each other. The possibility of proton transfer between monomers is discussed.

Anions↗