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Biomedical subjects

M Moritz

Publications and source records attributed to M Moritz.

At least 19 recordsLinked to original sources
PubMed2005

What is the best immunosuppression in living donor liver transplantation?

INTRODUCTION: As we have learned, there are no golden rules of immunosuppression in solid organ transplantation, and every transplant program is using its own regimen to prevent or treat rejection. We have retrospectively analyzed the incidence and severity of acute rejection in a consecutive series of living donor liver transplants. The major objective during the whole study period was to ultimately avoid any steroids from the beginning. METHODS: Twenty one adult patients and five children received 23 right, one left, and two left lateral lobe grafts from genetically or emotionally related living donors, including four ABO-incompatible pairs. The majority of patients had triple initial immunosuppression, based on tacrolimus, mycophenolate mofetil or sirolimus, and basiliximab or daclizumab. Except methylprednisolone administered before reperfusion in 13 patients, only seven had prednisolone after transplantation, and 12/26 had a completely steroid-free regimen. RESULTS: The overall incidence of biopsy-proven acute rejection was 4/21 in adults (19%) and 4/5 in children (80%). Rejections were mild in five and moderate in three cases, respectively, and easily reversed with steroids in all patients. Different combinations of immunosuppressive drugs or ABO incompatibility did not seem to have an influence on the risk of rejection. CONCLUSION: Despite the small number of patients in this series, completely steroid-free triple-drug immunosuppression with tacrolimus, mycophenolate mofetil, and basiliximab is safe and efficient to prevent acute rejection in adult recipients of living donor liver transplants. At least short-term administration of prednisolone should be considered in pediatric patients.

ABO Blood-Group System↗
PubMed2005

Aspirin and clopidogrel taken until 2 days prior to coronary artery bypass graft surgery is associated with increased postoperative drainage loss.

OBJECTIVE: Platelet aggregation inhibitors, such as aspirin and clopidogrel, are associated with increased bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. We investigated the impact of time between the last intake of aspirin and clopidogrel before CABG surgery and drainage loss, transfusion requirements and rate of reoperation. PATIENTS AND METHODS: The records of patients who had coronary artery bypass graft surgery (CABG) were reviewed for intake of aspirin and clopidogrel within 7 days prior to surgery. Drainage loss, transfusion requirements and rate of reoperation for bleeding within 5 days after the operation, were recorded. RESULTS: Out of 261 analysed patients, 225 patients (86.2 %) had no anti-platelet medication and 36 patients (13.8 %) were on aspirin and clopidogrel. Aspirin and clopidogrel, taken all until 2 days prior to operation, were associated with a significantly higher postoperative blood loss (1840 mL [1230 - 3710] vs. 280 mL [185 - 765], p = 0.005 for one day and 850 mL [345 - 1725] vs. 277 mL [165 - 778], p = 0.026, for 2 days prior to surgery). The trend showed that patients in the study group received more platelet concentrates (PC: 5.3 % vs. 13.9 %, p = 0.067). The rate of reoperation for bleeding was not different ( p = 0.25). CONCLUSION: Aspirin and clopidogrel up to 2 days prior to CABG were associated with a significantly higher postoperative drainage loss.

Aged↗
PubMed2004

Simulect induction facilitates Neoral-based steroid-free immunosuppression in primary kidney transplant recipients.

This study compares outcomes of kidney transplantation with two distinct induction protocols Basiliximab (Simulect) versus Muromonab (OTK 3) in the setting of cyclosporine (Neoral)-based immunosuppression. Postinduction protocols included either total prednisone avoidance or prednisone sparing versus standard prednisone dosing. Two hundred forty five adult patients receiving kidney transplantation between 1995 and 2000 were included in the study. Treatment in group 1 was OKT 3 + Neoral + adjunct + standard prednisone; group 2, Simulect + Neoral + adjunct + steroid sparing; group 3, Simulect + Neoral + adjunct + no prednisone. The demographics between all groups were similar. The mean (+/- SD) trough cyclosporine levels at 1 month were 276 +/- 128 versus 291 +/- 180 versus 398 +/- 365 (P=.020); at 3 months were 261 +/- 120 versus 280 +/- 152 versus 399 +/- 408 (P=.32); at 12 month were 235 +/- 144 versus 245 +/- 154 versus 234 +/- 132 (P=.96). Creatinine clearance at 1 month was 59 +/- 24 versus 58 +/- 18 versus 47 +/- 23 mL/min (P=.004); at 3 months was 66 +/- 28 versus 62 +/- 22 versus 53 +/- 25 mL/min (P=.007); at 12 months was 68 +/- 38 versus 65 +/- 22 versus 64 +/- 29 mL/min (P=.556). Serum creatinine at 1 month was 1.8 +/- 0.9 versus 1.6 +/- 1.2 versus 2.8 +/- 2.21 mg/dL (P=.005); at 3 months was 1.7 +/- 0.6 versus 1.9 +/- 1.0 versus 2.3 +/- 1.3 mg/dL (P=.007); at 12 months was 1.9 +/- 1.3 versus 2.1 +/- 1.0 versus 2.3 +/- 1.7 mg/dL (P=.179). The incidence of acute rejection within 1 year in the respective groups were 28% versus 15% versus 16%. Therefore, we conclude that using Simulect in transplant recipients results in long-term patient and graft survival similar to those achieved with OKT 3. The use of Simulect resulted in significant reduction in clinical rejection incidence within the first year regardless of steroid use. Thus, the use of Simulect allows complete steroid avoidance in Neoral-based immunosuppression regimen.

Antibodies, Monoclonal↗
PubMed2001

Impact of residual renal function in children on hemodialysis.

Residual renal function (RRF) contributes to dialysis adequacy as well as lower mortality and morbidity in dialysis patients. Even very small changes in glomerular filtration rate (GFR) account for considerable improvements in complications of dialysis. The purpose of this cross-sectional study is to determine the possible contribution of RRF to hemodialysis clearance and to compare the biochemical markers of this patient group with anuric patients. Ten patients with RRF on chronic hemodialysis for more than 6 months were enrolled in the study. Duration of dialysis was not different between the two patient populations. Average GFR was 3.4+/-2.6 ml/min in the group with RRF. Cholesterol, albumin, and triglyceride levels were not different between the groups. Residual renal urea clearance enhanced mean Kt/V of patients from 1.29 to 1.52. However erythropoietin and renin levels were higher in the group with RRF (P=0.019, P=0.044, respectively). There was a positive correlation between erythropoietin, renin levels, and average GFR of all patients (r=0.69, P=0.002, r=0.60, P=0.014). We conclude that RRF plays a greater role in pediatric patients on hemodialysis than previously recognized, and knowledge about patients' RRF should assist in improved overall management.

Adolescent↗
PubMed2001

Gamma-tubulin complexes and microtubule nucleation.

Microtubules are dynamic cytoskeletal polymers that assemble from alpha/beta-tubulin and are vital for the establishment of cell polarity, vesicle trafficking and formation of the mitotic/meiotic spindle. gamma-Tubulin, a protein related to alpha/beta-tubulin, is required for initiating the polymerization of microtubules in vivo. gamma-Tubulin has been found in two main protein complexes: the gamma-tubulin ring complex and its subunit, the gamma-tubulin small complex. The latter is analogous to the yeast Tub4 complex. In the past year, important advances have been made in understanding the structure and function of the gamma-tubulin ring complex and how it interacts with microtubules.

Animals↗
PubMed2001

GCP5 and GCP6: two new members of the human gamma-tubulin complex.

The gamma-tubulin complex is a large multiprotein complex that is required for microtubule nucleation at the centrosome. Here we report the purification and characterization of the human gamma-tubulin complex and the identification of its subunits. The human gamma-tubulin complex is a ring of ~25 nm, has a subunit structure similar to that reported for gamma-tubulin complexes from other species, and is able to nucleate microtubule polymerization in vitro. Mass spectrometry analysis of the human gamma-tubulin complex components confirmed the presence of four previously identified components (gamma-tubulin and gamma-tubulin complex proteins [GCPs] 2, 3, and 4) and led to the identification of two new components, GCP5 and GCP6. Sequence analysis revealed that the GCPs share five regions of sequence similarity and define a novel protein superfamily that is conserved in metazoans. GCP5 and GCP6, like other components of the gamma-tubulin complex, localize to the centrosome and associate with microtubules, suggesting that the entire gamma-tubulin complex takes part in both of these interactions. Stoichiometry experiments revealed that there is a single copy of GCP5 and multiple copies of gamma-tubulin, GCP2, GCP3, and GCP4 within the gamma-tubulin complex. Thus, the gamma-tubulin complex is conserved in structure and function, suggesting that the mechanism of microtubule nucleation is conserved.

Amino Acid Sequence↗
PubMed2000

Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.

Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.

Adolescent↗
PubMed2000

Structure of the gamma-tubulin ring complex: a template for microtubule nucleation.

The gamma-tubulin ring complex (gammaTuRC) is a protein complex of relative molecular mass approximately 2.2 x 10(6) that nucleates microtubules at the centrosome. Here we use electron-microscopic tomography and metal shadowing to examine the structure of isolated Drosophila gammaTuRCs and the ends of microtubules nucleated by gammaTuRCs and by centrosomes. We show that the gammaTuRC is a lockwasher-like structure made up of repeating subunits, topped asymmetrically with a cap. A similar capped ring is also visible at one end of microtubules grown from isolated gammaTuRCs and from centrosomes. Antibodies against gamma-tubulin label microtubule ends, but not walls, in centrosomes. These data are consistent with a template-mediated mechanism for microtubule nucleation by the gammaTuRC.

Animals↗
PubMed2000

Erythropoietin response to post-liver transplantation anemia.

Anemia frequently accompanies end-stage liver disease. Erythropoietin has recently been shown to be of benefit in a number of diseases complicated by anemia. We studied erythropoietin levels before and after orthotopic liver transplantation (OLT) and correlated these with the degree of anemia. Twenty-seven patients with end-stage cirrhosis who underwent OLT had preoperative and weekly postoperative serum erythropoietin levels determined by a highly sensitive radioimmunoassay. The relation of erythropoietin level to the values for hematocrit, serum creatinine, and cyclosporine and other biochemical test results was evaluated. Before transplantation, 23 patients were anemic; erythropoietin levels were appropriately elevated (72.7 +/- 37 mU/mL; normal, 10 to 15 mU/mL) for the degree of anemia (hematocrit, 33.1% +/- 1%) in 16 patients (70%). A blunted erythropoietin response to anemia was found in 7 of the anemic patients with cirrhosis (30%). After OLT, the hematocrit decreased to 29.5% +/- 0.6% at 4 weeks, with a reciprocal increase in serum erythropoietin levels to 36 +/- 5 mU/mL. Erythropoietin response appeared appropriate to the degree of anemia in 82% of the liver transplant recipients and blunted in 18%. We conclude that the ability to secrete erythropoietin in response to anemia is defective in many patients with end-stage liver disease, and a normal response may be restored after OLT. The results suggest that exogenous erythropoietin administration may be beneficial in anemic patients with cirrhosis and liver transplant recipients who have inappropriately low serum erythropoietin levels.

Adult↗
PubMed2000

Pregnancy in lung transplant recipients.

Eight female lung transplant recipients, all of whom became pregnant after transplant, were reported to the National Transplantation Pregnancy Registry from US transplant centers. Outcomes of the 8 pregnancies were 4 live births, 3 therapeutic abortions, and 1 spontaneous abortion. Three of the 4 newborns were premature, with low birth weight (< 2500 grams). Rejection during pregnancy occurred in 3 pregnancies (38%). All 8 transplant recipients reported at least 1 complication during pregnancy, including shortness of breath, rejection, and infection. Two of the 4 deliveries were by cesarean section. At follow-up, all children were developing well with no residual problems. Female lung transplant recipients may face higher risks during pregnancy than other solid organ transplant recipients.

Adult↗
PubMed1998

Recruitment of the gamma-tubulin ring complex to Drosophila salt-stripped centrosome scaffolds.

Extracting isolated Drosophila centrosomes with 2 M KI generates salt-resistant scaffolds that lack the centrosomal proteins CP190, CP60, centrosomin, and gamma-tubulin. To clarify the role of these proteins in microtubule nucleation by centrosomes and to identify additional centrosome components required for nucleation, we have developed an in vitro complementation assay for centrosome function. Centrosome aster formation is reconstituted when these inactive, salt-stripped centrosome scaffolds are supplemented with a soluble fraction of a Drosophila embryo extract. The CP60 and CP190 can be removed from this extract without effect, whereas removing the gamma-tubulin destroys the complementing activity. Consistent with these results, we find no evidence that these three proteins form a complex together. Instead, gamma-tubulin is found in two distinct protein complexes of 240,000 and approximately 3,000,000 D. The larger complex, which is analogous to the Xenopus gamma-tubulin ring complex (gammaTuRC) (Zheng, Y., M.L. Wong, B. Alberts, and T. Mitchison. 1995. Nature. 378:578-583), is necessary but not sufficient for complementation. An additional factor found in the extract is required. These results provide the first evidence that the gammaTuRC is required for microtubule nucleation at the centrosome.

Animals↗
PubMed1998

Casted titanium for dental applications: an XPS and SEM study.

Casted titanium for dental crowns has been investigated by means of X-ray Photoelectron Spectroscopy (XPS), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The samples were prepared according to the Ohara process. XRD analysis revealed that the investment consisted essentially of SiO2, Mg2P2O7, SiO2 x H2O and Mg2SiO4. SEM experiments combined with EDX analysis revealed the following atomic concentrations Si (62.6%), Mg (19.7%), P (17.1%), and Ca (0.6%). After casting, the titanium samples exhibit a rough and irregular surface, and XRD analysis indicated that titanium contains essentially the alpha phase and traces of the beta phase. After demoulding titanium samples, the investment side which was in contact with titanium was black colored, proving the reaction between titanium and the investment. XPS analysis performed on this side of the investment indicated that the Si 2p peak presents a shoulder on the low binding energy side and thus suggest that SiO2 has been transformed into metallic Si.

Chemical Phenomena↗
PubMed1998

[What is thought of the various surface treatments of biomaterials used in dental and maxillofacial implantology?].

The surface treatments for biomaterials have the following goals: to increase the biocompatibility and the tissue acceptation, to prevent infection to reduce the abrupt interfaces; to favour the biological integration and the long term in service behaviour. Advantages and inconveniences of these methods are analysed for the main biomaterials categories: metals, synthetic polymers, ceramics, materials of biological origin. In addition to appropriate physico-chemical and mechanical properties, the existence of biologically functional interfaces with the living cells is more and more wished. In the next 20 years, it appears likely that the design of prostheses or implants in actual clinical use will have to be totally or partly reconsidered.

Aluminum Oxide↗
PubMed1997

Surface characterization of C/Ti-6Al-4V coating treated with ion beam.

Surface of titanium alloy (Ti-6AI-4V) has been modified by ion beam mixing of thin C film. X-ray photoelectron spectroscopy analysis showed that after mixing, the surface film consists essentially of a Ti compound containing (Ti, O and C), TiO2, Ti and C contamination. The composition of the surface modified film determined by Rutherford backscattering spectrometry is approximately Ti0.5O0.3C0.2 and its thickness is about 200 nm. After three months immersion in a simulated body fluid, the growth of calcium phosphate species containing both HPO4- and H2PO4- (probably CaHPO4 and Ca(HPO4)2) have been observed. Titanium is found to be essentially composed of the Ti compound after immersion suggesting that both metallic Ti and TiO2 have dissolved.

Alloys↗
PubMed1995

Long-term results after primary restoration of the orbital floor.

It has been possible to follow-up 74 (54%) of the 137 patients who were treated for orbital floor fractures in our clinic between 1988 and 1992. The minimum observation time was 12 months. The results of the orbital reconstruction were analysed on the basis of the postoperative findings and the advantages of access via a central lower lid incision and the use of allogenic dura mater, were evaluated on the basis of the functional results. The biocompatibility, stability and ready availability of allogenic dura mater all support its use in orbital floor restoration. Nevertheless, the potential problems of CJD transmission are discussed.

Adolescent↗