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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 145 records · Page 8Linked to original sources
PubMed1999

Reduction of viral load and immune complex load on CD4+ lymphocytes as a consequence of highly active antiretroviral treatment (HAART) in HIV-infected hemophilia patients.

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load. MATERIALS AND METHODS: Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays. RESULTS: After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels. CONCLUSION: HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.

Anti-HIV Agents↗
PubMed1999

Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients.

Patients after organ transplantation are at an increased risk of microbial infections and might benefit from active vaccination. Due to therapeutic immunosuppression the efficacy of immunizations is, however, reduced and difficult to predict. Efficacy of vaccination against tick-borne encephalitis (TBE) using an abbreviated immunization schedule was compared in 31 heart transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation: 53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls. TBE vaccination was well tolerated by the transplant recipients; spectrum and frequency of adverse events were similar to controls. In the transplant patients, seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post-vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001) were markedly reduced in comparison to the control group. No clinical or demographic predictors of vaccination success could be established in the transplant patients. Due to the limited efficacy, TBE vaccination cannot be recommended as a routine procedure in heart transplant recipients at risk of TBE virus infection. TBE vaccination may be performed safely in selected cases, but repeated titre controls to confirm vaccination success would be required.

Adult↗
PubMed1999

Effect of long-term ACE inhibition on myocardial tissue in hypertensive stroke-prone rats.

The aim of the study was to investigate the influence of long-term ACE inhibition with ramipril on myocardial hypertrophy and its molecular background in spontaneously hypertensive stroke-prone rats (SHR-SP). Therefore, 1-month-old pre-hypertensive SHR-SP were randomized into three groups and exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive dose, RHI), 10 micrograms/kg/day ramipril (non-anti-hypertensive dose, RLO) or placebo. After 15 months cardiac tissue was collected from ten rats each for immunohistochemistry and Northern blot analysis of structural proteins, proteins of the extracellular matrix and several growth factors. Results showed that RHI, but not RLO, treatment prevented development of myocyte hypertrophy (ANP). Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no evidence of degeneration and loss of structural proteins (alpha -actinin), inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins (collagen, fibronectin, vimentin). Only in RHI-treated animals, mRNA levels for TGF- beta(1)as well as of collagen alpha(1)(I) and fibronectin were downregulated compared to placebo-treated animals. In contrast, VEGF mRNA levels increased significantly in both groups of ramipril-treated animals v. placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses of ramipril which is associated with prevention of hypertension and hypertrophy is accompanied by prevention of the development of necrosis and fibrosis. The role of VEGF, however, seems to be independent of this effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[Tibial growth after isolated femoral shaft fracture in the growth stage].

The aim of the present study is to investigate the growth of the tibia after femoral shaft fractures in children. We were able to follow up 44 patients (32 male and 12 female) after a mean of 8 years (range, 5 to 15 years). The age in the time of injury was 3 till 13 years (mean 7 years). The length of the femur, tibia and leg was measured on X-rays of the entire leg, and the measurements were compared with the contralateral side. A statistically significant number of tibial elongations were observed in fractures that had healed in considerable malalignment (at least 1 cm shortening, dislocation of at least a half of the breadth of the femoral shaft, angular deformity of more than 10 degrees) (p = 0.003) and in fractures that were subjected to manipulation (secondary reduction, change of treatment or traction weight) during the healing process (p = 0.007). Furthermore, all 7 patients who had infection requiring treatment at the tibial plateau extension had more pronounced tibial growth. No significant difference was found between tibial growth and the age of the child at the time of injury, the type of fracture, the location of fracture and the mode of treatment. The following factors were evaluated as being clinically relevant: primary, largely anatomic reduction, avoidance of secondary manipulation and prevention of infection at the tibial plateau extension.

Adolescent↗
PubMed1999

[Kidney and urinary tract diseases in pregnancy].

Management of urologic disorders in pregnant patients often increases the anxiety of all involved. Based on a thorough understanding of the physiologic changes seen in various organ systems the urologist has to assume the responsibility for the well-being of the mother and the fetus. Apart from the urinary tract infection, which occurs as frequent as in non-pregnant patients but has a significantly higher risk of acute bacterial pyelonephritis, it is mainly the pregnancy-associated symptomatic hydronephrosis and the urolithiasis which are complicating approximately 1 of every 1000-1500 pregnancies. Urinary tract infections should be treated in any case by antibiotics according to a antibiogram. High risk patients with history of vesicoureteral reflux or recurrent pyelonephritis should be treated prophylactically. Following parturition these patients should be investigated urologically to exclude structural abnormalities of the genitourinary system. In case of symptomatic hydronephrosis and calculous disease the first approach should be a watchful conservatism with symptomatic relief. If the symptoms persist insertion of a double-J-stent or in case of live-threatening situations (e.g. urosepsis) when urgent decompression and rapid evacuation is mandatory a percutaneous nephrostomy can be brought in place under sonographic monitoring completely thereby avoiding any radiation exposure.

Adult↗
PubMed1999

CD4 depletion in HIV-infected haemophilia patients is associated with rapid clearance of immune complex-coated CD4+ lymphocytes.

The predominant immunological finding in HIV+ haemophilia patients is a decrease of CD4+ lymphocytes during progression of the disease. Depletion of CD4+ lymphocytes is paralleled by an increase in the proportion of immune complex-coated CD4+ cells. We examined the hypothesis that the formation of immune complexes on CD4+ lymphocytes is followed by rapid clearance of immune complex-coated CD4+ lymphocytes from the circulation. In this study, the relationship of relative to absolute numbers of immune complex-loaded CD4+ blood lymphocytes and their association with viral load were studied. Two measurements of relative and absolute numbers of gp120-, IgG- and/or IgM-loaded CD4+ lymphocytes were analysed in HIV+ and HIV- haemophilia patients, with a median interval of approx. 3 years. Immune complexes on CD4+ lymphocytes were determined using double-fluorescence flow cytometry and whole blood samples. Viral load was assessed using NASBA and Nuclisens kits. Whereas the proportion of immune complex-coated CD4+ lymphocytes increased with progression of the disease, absolute numbers of immune complex-coated CD4+ lymphocytes in the blood were consistently low. Relative increases of immune complex-coated CD4+ blood lymphocytes were significantly associated with decreases of absolute numbers of circulating CD4+ lymphocytes. The gp120 load on CD4+ blood lymphocytes increased in parallel with the viral load in the blood. These results indicate that immune complex-coated CD4+ lymphocytes are rapidly cleared from the circulation, suggesting that CD4+ reactive autoantibodies and immune complexes are relevant factors in the pathogenesis of AIDS. Relative increases of immune complex-positive cells seem to be a consequence of both an increasing retroviral activity as well as a stronger loading with immune complexes of the reduced number of CD4+ cells remaining during the process of CD4 depletion. The two mechanisms seem to enhance each other and contribute to the progressive CD4 decrease during the course of the disease.

Antigen-Antibody Complex↗
PubMed1999

Oral or intravenous iron as an adjuvant to autologous blood donation in elective surgery: a randomized, controlled study.

BACKGROUND: This study was performed to evaluate the capacity of oral and intravenous (i.v.) iron administration during autologous blood donation (ABD) to improve the efficacy of ABD and to prevent the need for allogeneic blood transfusion in patients without iron deficiency who are undergoing major elective surgery for which a minimum of 3 autologous units have been ordered. STUDY DESIGN AND METHODS: One hundred twenty-three patients were enrolled in an open-labeled, randomized, controlled trial and assigned to three treatment groups: patients in Group 1 received 3 x 100 mg of Fe2+ per day given orally for 5 weeks before operation; patients in Group 2 received 200 mg of Fe3+ given intravenously after each donation combined with initial i.v. iron supplementation in patients with hemoglobin under 15 g per dL; and patients in Group 3 were in the control group that received no iron medication. A modest ABD program involving weekly phlebotomy and threshold hemoglobin values for donation of 11.5 g per dL in women and 12.0 g per dL in men was performed. RESULTS: Ninety patients, 15 women and 15 men in each of the three groups, completed the study. The mean net red cell production during ABD was no higher (p>0.2) in the iron-treated groups (Group 1: 473 +/- 178 mL; Group 2: 436 +/- 170 mL; Group 3 (controls): 397 +/- 174 mL). The mean number of autologous units donated per patient did not differ (p>0.7) among the groups (Group 1: 3.1 +/- 0.6; Group 2: 2.9 +/- 0.7; Group 3: 3.0 +/- 0.7). The proportion of patients who needed allogeneic blood transfusion showed no significant (p>0.4) advantage for iron treatment, (Group 1: 7%; Group 2: 20%; Group 3: 10%). CONCLUSION: In non-iron-deficient patients undergoing modest ABD without erythropoietin therapy, neither oral nor i.v. application of iron during the preoperative period enhances the success of preoperative ABD.

Administration, Oral↗
PubMed1999

Antibodies to private and public HLA class I epitopes in platelet recipients.

BACKGROUND: Transfusions or pregnancies can cause immunization against private HLA determinants and public epitopes shared by more than one private HLA antigen. HLA antibodies are correlated with febrile transfusion reactions, lower platelet response following platelet transfusion, and an increased rate of renal transplant rejection. Until now, antibody specificities in alloantisera from platelet recipients have been poorly characterized. STUDY DESIGN AND METHODS: Consecutive serum screens from platelet recipients were analyzed for antibodies against private HLA class I antigens and public HLA epitopes using a serum analysis program based on the 2 x 2 table analysis of correlations. Serum screens of highly immunized patients and of patients with new alloimmunization events were reviewed separately. RESULTS: Of the serum screens from 566 platelet recipients, 1577 indicated alloimmunization (panel-reactive antibodies >5%). The program assigned a specificity in 1024 of these screens (64.9%) and at least once in 522 of 566 patients (92.2%). In 267 patients, antibodies detecting public epitopes in the combined A- or B-locus cross-reacting groups were found; other public markers were detected in 39 patients. Patterns of reactivity were remarkably less stable than in patient groups previously studied. In many patients, antibodies with apparent private epitope specificity preceded the identification of antibodies against a shared marker of the same cross-reactive group. However, the disappearance of antibodies (whether or not this was followed by a new antibody against a private or public marker belonging to another cross-reacting group) was also observed. CONCLUSION: The computerized analysis of microlymphocytotoxicity tests enhances the rate of antibody specification in sera from platelet recipients with lymphocytotoxic antibodies. The identified antibodies should be taken into account in the selection of platelet donors. The data confirm and extend previous observations on HLA class I antibodies and elucidate new alloimmunization events.

Antibodies↗
PubMed1999

The influence of automated plateletpheresis on systemic levels of hematopoietic growth factors.

BACKGROUND: Megakaryocytopoiesis and platelet production are regulated by several hematopoietic growth factors. The present study focuses on the effects of automated plateletpheresis on systemic levels of different hematopoietic growth factors. STUDY DESIGN AND METHODS: Platelet count, mean platelet volume, and serum levels of thrombopoietin, erythropoietin, interleukin-1beta, interleukin-6, and stem cell factor in 21 healthy donors were measured before platelet collection, after the first half of the apheresis procedure, at the end of apheresis, and on Days 1, 2, and 7 thereafter. RESULTS: Thrombopoietin levels (initial level: 49.5 +/- 25.5 pg/mL) showed a significant increase between measurements taken at the end of apheresis and Day 1 (56.9 +/- 26.7 pg/mL; p = 0.01). There was a highly significant decrease in stem cell factor levels during apheresis (p<0.0005), reaching preapheresis values (1679 +/- 210 pg/mL) on Day 1. A highly significant increase in erythropoietin levels (initial level: 7.5 +/- 4.0 U/L) was seen after apheresis (p<0.0005 on Days 1 and 2). The level remained significantly elevated until Day 7 (p = 0.004). Interleukin-1beta and interleukin-6 levels (before donation: 1.4 +/- 1.8 pg/mL and 1.1 +/- 0.7 pg/mL, respectively) did not change during the observation period. Thrombopoietin levels correlated consistently and inversely with stem cell factor levels after apheresis (Day 1, r = -0.46, p = 0.035; Day 2, r = -0.50, p = 0.02; Day 7, r = -0.50, p = 0.02). CONCLUSION: The data show a coordinated response of the hematopoietic system to platelet loss. It is suggested that the decrease in serum stem cell factor levels during apheresis reflects the consumption of stem cell factor by early hematopoietic progenitors that expand to initiate early megakaryocytopoiesis. The temporary increase in thrombopoietin is the result of platelet loss and serves as a stimulus for subsequent thrombopoiesis. The pronounced elevation of erythropoietin after apheresis suggests a role for this primarily erythropoietic cytokine in thrombopoiesis, too.

Adolescent↗
PubMed1999

Comparison of the performance of four microtube column agglutination systems in the detection of red cell alloantibodies.

BACKGROUND: The purpose of this study was to compare the performance of four currently available microtube column agglutination systems in the detection of red cell alloantibodies to that of the standard tube low-ionic-strength solution (LISS) indirect antiglobulin test (IAT) (tube LISS-IAT). STUDY DESIGN AND METHODS: In a comparative study, 172 sera, previously demonstrated to contain red cell alloantibodies, were tested in parallel by the tube LISS-IAT and three microtube column agglutination techniques (DiaMed-ID, Ortho BioVue, and Sanofi-Pasteur Scangel) and one affinity-adherence test system (Gamma ReACT). Tests were performed simultaneously by a single person on freshly thawed sera that had been frozen at -20 degrees C. RESULTS: The rate of detection of clinically significant alloantibodies (n = 154) in microtube column systems was very similar. One hundred forty-one sera (91.6%) reacted in the DiaMed-ID, 139 (90.3%) in the ReACT, 139 (90.3%) in the BioVue, and 142 (92.2%) in the Scangel. Only 117 (76.0%) of these sera reacted in the tube LISS-IAT. The detection rates for 18 antibodies of minor clinical significance (anti-M, -N, -P1, -Le(a), and -Le(b)) varied among the test systems: DiaMed-ID, 5 (28%); ReACT, 7 (39%); BioVue, 14 (78%); Scangel, 10 (56%); and tube LISS-IAT, 6 (33%). Antibody reactivity as determined by titer and score was very similar in all microtube column systems and higher in these systems than in the tube LISS-IAT. CONCLUSION: The sensitivity of all four microtube column systems in the detection of clinically significant red cell alloantibodies was similar and was markedly superior to that of the tube LISS-IAT. An individual cost-benefit analysis should be performed in every institution to decide whether a microtube column system should be applied. If so, the antibody screen in the microtube column agglutination system should ideally be performed in advance of the crossmatch to provide time to screen for compatible units.

Erythrocytes↗
PubMed1999

An analysis of errors in blood component transfusion records with regard to quality improvement of data acquisition and to the performance of lookback and traceback procedures.

BACKGROUND: Quality assurance of blood transfusion covers institutions, personnel, and procedures involved in preparing, issuing, and using blood components. The accuracy of data related to blood component transfusions is a tool for quality control in the transfusion service. STUDY DESIGN AND METHODS: A study of the accuracy of data records of the transfusion service at the University Hospital of Erlangen, Germany, between June 1994 and May 1996 was carried out. All returned blood component transfusion report forms were examined for discrepancies between primary data records and clinical transfusion reports. RESULTS: Blood components (n = 49,224) from allogeneic and autologous donations, packed red cells, fresh-frozen plasma, and platelet components that had been issued for transfusion were included in this evaluation. For 27.3 percent of all components issued, no transfusion report was returned to the blood bank. For the remaining 35,786 units, errors were found in 3.8 percent of the records. For 1.24 percent of all components, discrepant information related to the recipient's identity or the component's status was found; this affected the feasibility of lookback or traceback searches. CONCLUSION: A remarkably high frequency of discrepancies exists between computerized blood bank records and the information recorded on returned blood transfusion forms. The processes of data acquisition and entry must be included in quality assurance efforts in transfusion medicine.

Blood Banks↗
PubMed1999

Fetal ultrasound biometry: 1. Head reference values.

OBJECTIVE: To create reliable reference ranges and calculate Z scores for fetal head ultrasound biometry using a large sample size which is evenly distributed from 12 to 42 weeks of pregnancy. DESIGN: A prospective, cross-sectional study. SETTING: Obstetric clinics (outpatient and delivery units) at the University Hospital of Zurich. SAMPLE: The study data were obtained from 6557 pregnant women. METHODS: Only the first ultrasound examination between 12 and 42 weeks of each fetus with exactly established gestational age was used for analysis. No exclusions were made on the grounds of small-for-date birthweight, prematurity or other events several weeks after the examination. Separate regression models were fitted to estimate the mean and standard deviation at each gestational age for each parameter. RESULTS: A total of 6217 fetal head biparietal diameters and 5510 occipito-frontal diameters were measured. Both head circumference and cephalic index were derived in 5462 cases where both biparietal diameter and occipito-frontal diameter could be measured on the same fetus. The centile charts, tables and regression formulae for biparietal and occipito-frontal diameters, head circumference and cephalic index are presented. An application to calculate Z scores was developed using Excel (Microsoft Corporation, USA) and macros are presented in detail in the Figure 8 footnote. The comparison of our charts with those of the two most recent studies revealed almost no differences in biparietal diameter centiles. In one publication, occipito-frontal diameter charts, and in another, head circumference charts were different from the current study. CONCLUSIONS: We have presented centile charts, tables and regression formulae for fetal head ultrasound biometry derived from a large and minimally selected sample size in a carefully designed cross-sectional study. Complete tables and regression formulae to calculate reference ranges and Z scores are presented for use in computer-aided evaluation of fetal ultrasound biometry.

Adult↗
PubMed1999

Fetal ultrasound biometry: 2. Abdomen and femur length reference values.

OBJECTIVE: To create reliable reference ranges and calculate Z scores for fetal abdomen and femur ultrasound biometry using a large sample size which is evenly distributed from 12 to 42 weeks of pregnancy. DESIGN: A prospective, cross-sectional study. SETTING: Obstetric clinics (outpatient and delivery units) at the University Hospital of Zurich. SAMPLE: The study data were obtained from 6557 pregnant women. METHODS: Only the first ultrasound examination between 12 and 42 weeks of each fetus with certainly established gestational age was used for analysis. No exclusions were made on the grounds of small-for-date birthweight, prematurity or other events several weeks after the examination. Separate regression models were fitted to estimate the mean and standard deviation at each gestational age for each parameter. RESULTS: A total of 5807 mean abdominal diameters and abdominal circumferences were derived from fetal transverse and anterio-posterior fetal abdominal diameter measurements. Fetal femur length was measured in 5860 instances. The charts, tables and regression formulae of the biometrical measurements are presented. A comparison of our charts with others showed no significant difference. Only Merz's centiles for abdominal biometry were lower and for femur length higher than ours. An application to calculate Z scores was developed using Excel (Microsoft Corporation, USA); the macros are presented in detail in the Figure 6 footnote. CONCLUSIONS: We have presented centile charts, tables and formulae for fetal abdominal diameter and circumference and femur length derived from a large and minimally selected sample size in a carefully designed cross-sectional study. Complete tables and regression formulae to calculate reference ranges and Z scores are presented to use in computer-aided evaluation of fetal ultrasound biometry.

Abdomen↗
PubMed1999

A Scj1p homolog and folding catalysts present in dog pancreas microsomes.

Dog pancreas microsomes represent the key components of the established model system for the analysis of protein transport into the mammalian endoplasmic reticulum. More recently, these microsomes were also employed in cell-free systems which address questions related to protein folding and protein degradation in the mammalian endoplasmic reticulum. In order to get at a complete picture of these undoubtedly related processes in the in vitro system we need to know all the proteins we are dealing with, and their respective stoichiometries. Here we give a progress report on our attempts to identify and to quantify the soluble molecular chaperones and folding catalysts which are present in the lumen of dog pancreas microsomes. Eventually, we will need to know how the in vitro system compares with the situation in intact pancreatic cells as well as in other cells.

Amino Acid Sequence↗
PubMed1999

Cytokine generation in whole blood, leukocyte-depleted and temporarily warmed red blood cell concentrates.

BACKGROUND AND OBJECTIVES: It has been suggested that inflammatory cytokines such as Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 might be responsible for a large number of non-antibody-mediated adverse reactions to the transfusion of blood components, especially of platelet concentrates (PCs). The aim of this study was to compare the levels of proinflammatory cytokines in different blood components containing red cells such as buffy-coat-free packed red cells (RBCs), filtered RBCs and whole blood (WB) during storage under several conditions. MATERIALS AND METHODS: WB (CPD-A1, n = 16) was stored for 35 days at 2-6 degrees C; samples were taken on days 0, 21 and 35. Buffy-coat-poor RBCs in additive solution PAGGS-M (n = 16) were divided into halves, one half was leukocyte (WBC)-depleted by filtration on day 0, both halves were stored for 49 days at 2-6 degrees C (samples: days 0, 21, 49). Furthermore, buffy-coat-poor, unfiltered SAG-M RBCs (n = 16) were halved immediately after production and stored at 2-6 degrees C until day 42 (samples: days 0, 21, 42). One half remained at room temperature for 24 h on day 3. Cytokine levels were determined with commercial enzyme-linked immunosorbent assays. RESULTS: Levels of IL-1beta and TNF-alpha rose during storage of WB and RBCs. IL-6 could be detected markedly above the detection threshold in WB only. At the end of storage, we detected IL-8 in 1 of 16 units of WB tested, in 10 of 16 standard PAGGS-M RBCs and in 15 of 16 temporarily warmed SAG-M RBCs. Prestorage filtration of RBCs prevented the accumulation of IL-1beta and TNF-alpha. Temporarily warming of RBCs for 24 h did not cause any substantial increase in cytokine levels other than IL-8. RBCs stored in different additive solutions (PAGGS-M versus SAG-M) showed similar cytokine concentrations during storage. The cytokine content of WB was very similar to that of buffy-coat-poor RBCs. CONCLUSION: Cytokine levels measured in WB and buffy-coat-poor RBCs result in levels which are unlikely to cause febrile reactions even in the case of massive transfusion. We conclude that, according to present knowledge, there is no reason for prestorage filtration of buffy-coat-poor RBCs or WB to avoid febrile transfusion reactions due to cytokine accumulation during storage.

Blood Preservation↗