Biomedical subjects

Robert Zimmermann

Publications and source records attributed to Robert Zimmermann.

50 records · Page 3Linked to original sources

PubMed2003

Treatment of distal radioulnar joint disorders with a modified Sauvé-Kapandji procedure: long-term outcome with special attention to the DASH Questionnaire.

INTRODUCTION: An intact distal radioulnar joint (DRUJ) is essential for normal functioning of the upper limb. Osteoarthritis of the DRUJ often leads to ulnar wrist pain, limitation of forearm rotation and reduced grip strength, all of which limit activities of daily living. Once the joint is damaged, salvage procedures are recommended. MATERIALS AND METHODS: Between 1986 and 1996 a modified Sauvé-Kapandji procedure was performed in 117 patients with painfully limited forearm rotation and osteoarthritis of the distal radioulnar joint (DRUJ). Of the 117 patients, 73 women and 32 men, whose ages at operation ranged from 22 to 74 years (average 58 years), were retrospectively reviewed clinically and radiologically 8 years (range 5-12 years) after the operation. The DASH questionnaire was used with 53 patients, 43 patients were accepted for the study, and 10 were excluded. RESULTS: Forearm rotation improved in all patients, ulnar wrist pain was reduced in 97% of the patients, and 9% had mild pain at the proximal ulnar stump. Grip strength improved from a preoperative mean of 38% to a postoperative mean of 55% compared with the contralateral side. The mean DASH score was 28 points (range 0-53 points). In all cases the arthrodesis fused within 8 weeks. The radiographs showed approximation between the proximal ulna stump and the radius compared with the preoperative situation in 74% of the patients. CONCLUSION: Our clinical and radiological findings suggest that the Sauvé-Kapandji procedure is indicated in symptomatic, non-reconstructable disorders of the DRUJ. The DASH questionnaire provides a general view of the functional outcome after the Sauvé-Kapandji procedure. The DASH questionnaire is very helpful in evaluating the effect of the Sauvé-Kapandji procedure on the entire upper limb.

Adult↗

PubMed2003

Injectable calcium phosphate bone cement Norian SRS for the treatment of intra-articular compression fractures of the distal radius in osteoporotic women.

BACKGROUND: Distal radius fracture often presents a metaphyseal void which is more extended in elderly, osteoporotic patients. Bone graft and bone substitutes are reported to be beneficial in maintaining metaphyseal reduction. METHODS: We performed a prospective study on 52 menopausal, osteoporotic women with unstable intra-articular distal radius fractures to compare the outcome of percutaneous pinning and immobilisation in a cast for 6 weeks with that using injectable calcium phosphate bone cement (Norian Skeletal Repair System, SRS) to supplement pin and screw fixation and immobilisation in a cast for 3 weeks. All patients were reviewed 2 years (range 21-29 months) after surgery. RESULTS: Patients treated with SRS had better functional outcome, restoration of movement and grip strength ( p<0.001). In this group there was 1 mm loss of radial length, 3 degrees loss of radial inclination and 7 degrees loss of palmar tilt. In the control group radial length decreased 3 mm, radial inclination decreased 11 degrees and palmar tilt 12 degrees. Loss of reduction was significantly higher in the control group ( p<0.001). CONCLUSION: We conclude that the use of Norian SRS to supplement pin and screw fixation is effective in maintaining the reduction of unstable intra-articular distal radius fractures in osteoporotic patients and provides a better clinical outcome than percutaneous pinning.

Aged↗

PubMed2003

In vitro quality control of red blood cell concentrates outdated in clinical practice.

The properties of red blood cell (RBC) concentrates stored in different additive solutions have been previously examined under laboratory conditions at the end of shelf-life. However, whether these data are representative for RBC units used in clinical practice has not been shown. Therefore, we examined 164 RBC units from six manufacturers outdated after clinical usage in a hospital-based transfusion service for cellular content, hemolysis, adenosin triphosphate, 2,3-DPG, pH, oxygen saturation and levels of beta-thromboglobulin and proinflammatory cytokines interleukin (IL) 1beta (IL-1), IL-6, IL-8 and tumor necrosis factor alpha (TNFalpha). Results were correlated with the number of interruptions of recommended storage conditions and with different manufacturers. TNFalpha and IL-8 levels in the supernatant of RBC concentrates showed a weak correlation with the number of interruptions of recommended storage conditions (TNFalpha: r = 0.25, P < 0.01; IL-8: r = 0.20, P < 0.01) for the whole series. We detected no significant correlation between hemolysis and interruptions of recommended storage conditions or any of the remaining studied parameters. However, we found significant differences between RBC concentrates supplied by different manufacturers with respect to cellular content and most of the studied parameters. RBC concentrates containing SAG-M from one single manufacturer had higher in vitro hemolysis at the end of shelf-life compared to all other manufacturers (P < 0.05). We conclude from our data that interruptions of optimal conditions for storage of red cell components during cross-match testing and transport in our setting play a minor role for in vitro properties of RBC units at the end of shelf-life. The influence of processes of production, storage and/or transport until entry of RBC units into our blood component depot seems to be much more important for final product quality at the end of shelf-life than subsequent events.

Blood Preservation↗

PubMed2003

Sinus floor augmentation with beta-tricalciumphosphate (beta-TCP): does platelet-rich plasma promote its osseous integration and degradation?

When dental implants are to be inserted, sinus floor augmentation is an effective treatment procedure to improve bone height in the posterior maxilla. In addition to autogenous bone material, allogenic materials, e.g. beta-tricalciumphosphate (beta-TCP), have been used successfully. The purpose of this study was to investigate whether the combination of beta-TCP with platelet-rich plasma (PRP) enhances bony regeneration and resorption of the tricalciumphosphate material. In a randomized prospective trial, 45 sinus floor elevations were performed in 39 patients. In 22 sites, PRP was added to the beta-TCP granules, while in 23 sites beta-TCP without PRP was used. Six months later, bone specimens were harvested from the augmented region during the implant insertion procedure. The formation of new bone was about 8-10% higher when PRP was applied. A faster degradation of the ceramic bone substitute was not observed. In conclusion, when PRP was added to beta-TCP, bone regeneration was supported to a small extent. However, the resorption of beta-TCP was not accelerated and foreign-body giant cells and soft tissue surrounding the beta-TCP granules were present.

Absorbable Implants↗

PubMed2003

Structure of the L1 protuberance in the ribosome.

The L1 protuberance of the 50S ribosomal subunit is implicated in the release/disposal of deacylated tRNA from the E site. The apparent mobility of this ribosomal region has thus far prevented an accurate determination of its three-dimensional structure within either the 50S subunit or the 70S ribosome. Here we report the crystal structure at 2.65 A resolution of ribosomal protein L1 from Sulfolobus acidocaldarius in complex with a specific 55-nucleotide fragment of 23S rRNA from Thermus thermophilus. This structure fills a major gap in current models of the 50S ribosomal subunit. The conformations of L1 and of the rRNA fragment differ dramatically from those within the crystallographic model of the T. thermophilus 70S ribosome. Incorporation of the L1-rRNA complex into the structural models of the T. thermophilus 70S ribosome and the Deinococcus radiodurans 50S subunit gives a reliable representation of most of the L1 protuberance within the ribosome.

Amino Acid Sequence↗

PubMed2003

Cord blood processing with an automated and functionally closed system.

BACKGROUND: Umbilical cord blood processing with standard centrifugation techniques is performed in open systems and results in varying cell and volume recoveries. STUDY DESIGN AND METHODS: Forty umbilical cord blood donations were randomly assigned to processing either with a microprocessor-controlled cell separator equipped with closed disposables or with a manual separation procedure in blood bags. The collection efficiency of nucleated cells, MNCs, RBCs, and CD34+ cells and the processing time were analyzed. RESULTS: Using the cell processor, mean collection efficiencies were 78.6 +/- 24.9 percent for nucleated cells, 77.4 +/- 27.8 percent for MNCs, 55.5 +/- 14.6 percent for RBCs, and 83.6 +/- 32.5 percent for CD34+ cells, while they were 73.1 +/- 13.2 percent for nucleated cells, 78.1 +/- 14.9 percent for MNCs, 26.0 +/- 12.2 percent for RBCs, and 77.0 +/- 17.6 percent for CD34+ cells when using the standard centrifugation technique. The processing time was about 20 minutes for automated processing and 60 to 80 minutes for the standard centrifugation technique. CONCLUSION: Using the new cell processor, the collection efficiencies for nucleated cells, MNCs, and CD34+ cells are similar to those obtained by established centrifugation techniques while the RBC reduction is less effective. The main advantages of the new systems are the closed system, the more standardized processing procedure, and a significantly shorter processing time.

Antigens, CD34↗

PubMed2003

Comparison of two apheresis systems for the collection of CD14+ cells intended to be used in dendritic cell culture.

BACKGROUND: Monocytes collected by leukapheresis are increasingly used for dendritic cell (DC) culture in cell factories suitable for DC vaccination in cancer. STUDY DESIGN AND METHODS: Using modified MNC programs on two apheresis systems (Cobe Spectra and Fresenius AS.TEC204), leukapheresis components collected from 84 patients with metastatic malignant melanoma and from 31 healthy male donors were investigated. MNCs, monocytes, RBCs, and platelets (PLTs) in donors and components were analyzed by cell counters, WBC differential counts, and flow cytometry. RESULTS: In 5-L collections, Astec showed better results regarding monocyte collection rates (11.0 vs. 7.4 x 10(6)/min, p = 0.04) and efficiencies (collection efficiency, 51.9 vs. 31.9%; p < 0.001). Both devices resulted in monocyte yields at an average of 1 x 10(9) (donors) and 2.5 x 10(9) (patients), whereas Astec components contained high residual RBCs. Compared to components with low residual PLTs, high PLT concentration resulted in higher monocyte loss (48 vs. 20%, p < 0.0001) before DC culture. CONCLUSION: The Astec is more efficient in 5-L MNC collections compared to the Spectra. Components with high residual PLTs result in high MNC loss by purification procedures. Thus, optimizing MNC programs is essential to obtain components with high MNC yields and low residual cells as prerequisite for high DC yields.

Adult↗

PubMed2003

Letting lipids go: hormone-sensitive lipase.

PURPOSE OF REVIEW: Despite their pathophysiological importance, the molecular mechanisms and enzymatic components of lipid mobilization from intracellular storage compartments are insufficiently understood. The aim of this review is to evaluate the role of hormone-sensitive lipase in this process. RECENT FINDINGS: Hormone-sensitive lipase exhibits a broad specificity for lipid substrates such as triglycerides, diglycerides, cholesteryl esters, and retinyl esters and the enzyme is in a wide variety of tissues. The high enzyme activity in adipose tissue was considered rate-limiting in the degradation of stored triglycerides. This view of a single enzyme controlling the catabolism of stored fat was challenged by recent findings that in hormone-sensitive lipase deficient mice adipose tissue triglycerides were still hydrolyzed and that these animals were leaner than normal mice. These results indicated that in adipose tissue hormone-sensitive lipase cooperates with other yet unidentified lipases to control the mobilization of fatty acids from cellular depots and that this process is coordinately regulated with lipid synthesis. Induced mutant mouse lines that overexpress or lack hormone-sensitive lipase also provided evidence that hormone-sensitive lipase-mediated cholesteryl ester hydrolysis is involved in steroid-hormone production in adrenals and affects testis function. Finally, hormone-sensitive lipase deficiency in mice results in a lipoprotein profile characterized by low triglyceride and VLDL levels and increased HDL cholesterol concentrations. SUMMARY: The 'anti-atherosclerotic' plasma lipoprotein profile and the fact that hormone-sensitive lipase deficient animals become lean identifies the inhibition of hormone-sensitive lipase as a potential target for the treatment of lipid disorders and obesity.

Adipose Tissue↗

PubMed2003

Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice.

Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine whether a hepatic TG content lower than normal, as observed in HSL-knockout mice, leads to increased hepatic insulin sensitivity. Therefore, hyperinsulinemic clamp experiments in combination with D-(3)H-glucose were used. Furthermore, hepatic insulin receptor and phosphorylated protein kinase B (PKB-P)/akt were analyzed by Western blotting. No significant differences where observed in insulin-mediated whole-body glucose uptake between HSL-knockout and control mice. Interestingly, hepatic insulin sensitivity of HSL-knockout mice was increased, because insulin caused a greater reduction in endogenous glucose production ( approximately 71% compared with approximately 31% in control mice; P < 0.05), despite decreased plasma adiponectin levels. PKB/akt phosphorylation and phosphatidylinositol-3-kinase activity was significantly higher in livers of HSL-knockout mice after insulin stimulation. In HSL-knockout mice, reduced hepatic TG stores result in an increased suppressive effect of insulin on hepatic glucose production, in line with an increased hepatic PKB-P/akt and phosphatidylinositol-3 kinase activity. Thus, hepatic insulin sensitivity is indeed increased after reducing hepatic TG stores below normal.

Adiponectin↗

PubMed2002

Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity.

Endothelial cell-derived lipase (EDL) is a new member of the lipase gene family with high sequence homology with lipoprotein lipase (LPL). EDL is a phospholipase with very little triacylglycerol lipase activity. To investigate the effects of EDL on binding and uptake of high-density lipoprotein (HDL), as well as on the selective uptake of HDL-derived cholesterol esters (CEs), HepG2 cells were infected with adenovirus coding for EDL. For comparison, cells were also infected with LPL and with lacZ as a control. Both HDL binding and particle uptake were increased 1.5-fold and selective HDL-CE uptake was increased 1.8-fold in EDL-infected HepG2 cells compared with controls. The effect of LPL was less pronounced, resulting in 1.1-fold increase in particle uptake and 1.3-fold increase in selective uptake. Inhibition of the enzymic activity with tetrahydrolipstatin (THL) significantly enhanced the effect of EDL, as reflected by a 5.2-fold increase in binding, a 2.6-fold increase in particle uptake and a 1.1-fold increase in CE selective uptake compared with incubations without THL. To elucidate the mechanism responsible for the effects of THL, we analysed the abundance of heparin-releasable EDL protein from infected HepG2 cells upon incubations with THL, HDL and free (non-esterified) fatty acids (FFAs). In the presence of THL, vastly more EDL protein remained bound to the cell surface. Additionally, HDL and FFAs reduced the amount of cell-surface-bound EDL, suggesting that fatty acids that are liberated from phospholipids in HDL release EDL from the cell surface. This was substantiated further by the finding that, in contrast with EDL, the amount of cell-surface-bound enzymically inactive mutant EDL (MUT-EDL) was not reduced in the presence of HDL and foetal calf serum. The increased amount of cell-surface-bound MUT-EDL in the presence of THL suggested that the enzymic inactivity of MUT-EDL, as well as an augmenting effect of THL that is independent of its ability to inactivate the enzyme, are responsible for the increased amount of cell-surface-bound EDL in the presence of THL. Furthermore, in cells expressing MUT-EDL, binding and holoparticle uptake were markedly higher compared with cells expressing the active EDL, and could be increased further in the presence of THL. Despite 1.7-fold higher binding and 1.8-fold higher holoparticle uptake, the selective CE uptake by MUT-EDL-expressing cells was comparable with EDL-expressing cells and was even decreased 1.3-fold with THL. Experiments in CLA-1 (CD-36 and LIMPII analogous 1, the human homologue of scavenger receptor class B type I)-deficient HEK-293 cells demonstrated that EDL alone has the ability to stimulate HDL-CE selective uptake independently of CLA-1. Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1.

Adenoviridae↗

PubMed2002

Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle.

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.

Adipose Tissue↗

PubMed2002

Preparation of FFP as a by-product of plateletpheresis.

BACKGROUND: To reduce the production costs of single-donor platelets (SDPs), a study was conducted to investigate whether plasma collected as a by-product of plateletpheresis satisfies the quality requirements for FFP without impairing the quality of the SDP component. STUDY DESIGN AND METHODS: Ninety-two donors with platelet (PLT) counts <270 x 10(9) per L underwent plateletpheresis using an automated cell separator (Spectra Apheresis System with the Leukoreduction System [LRS], Gambro BCT, Lakewood, CO). The machine was programmed to collect 3 x 10(11) PLTs in 250 mL of plasma with an additional unit of 350 mL of plasma or 3 x 10(11) PLTs in 250 mL of plasma without additional plasma in 10 procedures. FV and FVIII and residual RBCs, WBCs, and PLTs in the plasma were measured for quality control. RESULTS: FV was 0.87 +/- 0.18 IU per mL, and FVIII was 1.32 +/- 0.48 IU per mL in the plasma components (n = 41). The recovery was 94.1 +/- 5.5 percent for FV and 102.2 +/- 9.5 percent for FVIII when compared with the donors' predonation values. Residual cells were 0.002 +/- 0.009 x 10(9) RBCs per L (n = 30), 12 +/- 6 x 10(9) PLTs per L (n = 30), and 0.32 +/- 0.37 x 10(6) WBCs per L (n = 92). CONCLUSIONS: Using the automated cell separator and special software, it is possible to collect plasma as a by-product of plateletpheresis that meets the properties requested for FFP without impairing the quality of the SDP components. The content of clotting factors is within the requested range for FFP. Residual cell counts are within all European and U.S. specifications for FFP, and the WBC content even satisfies the criteria for WBC-reduced blood components. The collection of FFP as a by-product does not cause any additional costs and thus helps to reduce the costs in preparing blood components.

Adult↗

PubMed2002

Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism.

PURPOSE OF REVIEW: The aim of this review is to summarize and discuss recent advances in the understanding of the physiological role of lipoprotein lipase in lipid and energy metabolism. RECENT FINDINGS: Studies on the transcriptional and the posttranscriptional level of lipoprotein lipase expression have provided new insights into the complex mechanisms that are involved in the regulation of the enzyme. Additionally a large body of evidence from both human studies and animal models suggests that the level of lipoprotein lipase expression in a given tissue is the rate limiting process for the uptake of triglyceride derived fatty acids. Imbalances in the partitioning of fatty acids among peripheral tissues have major metabolic consequences. For example, in mice both decreased lipoprotein lipase activities in adipose tissue and increased activity in muscle are associated with resistance to obesity; lack of lipoprotein lipase activity in macrophages is correlated with a decreased susceptibility to develop atherosclerotic lesions and overexpression of the enzyme in muscle is associated with increased blood glucose levels and insulin resistance. SUMMARY: Considering the central role of lipoprotein lipase in energy metabolism it is a reasonable goal to discover and develop new drugs that affect the tissue specific expression pattern of the enzyme.

Animals↗

PubMed2001

Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis.

Hormone-sensitive lipase (HSL) is expressed predominantly in white and brown adipose tissue where it is believed to play a crucial role in the lipolysis of stored triglycerides (TG), thereby providing the body with energy substrate in the form of free fatty acids (FFA). From in vitro assays, HSL is known to hydrolyze TG, diglycerides (DG), cholesteryl esters, and retinyl esters. In the current study we have generated HSL knock-out mice and demonstrate three lines of evidence that HSL is instrumental in the catabolism of DG in vivo. First, HSL deficiency in mice causes the accumulation of DG in white adipose tissue, brown adipose tissue, skeletal muscle, cardiac muscle, and testis. Second, when tissue extracts were used in an in vitro lipase assay, a reduced FFA release and the accumulation of DG was observed in HSL knock-out mice which did not occur when tissue extracts from control mice were used. Third, in vitro lipolysis experiments with HSL-deficient fat pads demonstrated that the isoproterenol-stimulated release of FFA was decreased and DG accumulated intracellularly resulting in the essential absence of the isoproterenol-stimulated glycerol formation typically observed in control fat pads. Additionally, the absence of HSL in white adipose tissue caused a shift of the fatty acid composition of the TG moiety toward increased long chain fatty acids implying a substrate specificity of the enzyme in vivo. From these in vivo results we conclude that HSL is the rate-limiting enzyme for the cellular catabolism of DG in adipose tissue and muscle.

Adipose Tissue↗