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Biomedical subjects

M Horst

Publications and source records attributed to M Horst.

At least 19 recordsLinked to original sources
PubMed2001

Analysis of the risk of transmitting bovine spongiform encephalopathy through bone grafts derived from bovine bone.

Bone substitutes of bovine origin are widely used for treatment of bone defects in dental and orthopedic surgery. Due to the occurrence of BSE and the new variant of Creutzfeldt Jakob Disease risks of transmitting diseases through the use of such materials need to be carefully evaluated. Risk analysis can either be based on theoretical assessments or experimental evidence. Here we present a comparative study on two bovine bone substitutes (Bio-Oss and Osteograf/N) which is based on theoretical values. Furthermore, for one of these materials, i.e. Bio-Oss, the prion inactivation capacity of one of the production steps was experimentally evaluated. Theoretical and experimental data indicate that the use of these materials does not carry a risk of transmitting BSE to patients.

Animals↗
PubMed2001

[Postappendectomy abscess--the role of fecoliths].

Intraabdominal abscess formation is the most common septical complication after perforated appendicitis. An appendiceal fecalith favours appendicitis and is a high risk for complications like perforation or abscess formation. In a 6 year period 554 patients have been treated operatively for appendicitis in our institution. In 4 patients, 6 to 12 1/2 years, operated for perforated appendicitis, a fecalith was initially overlooked. This unrecognised fecalith at operation led to an intraabdominal abscess 14 days up to 17 months postoperatively. After laparatomy with extraction of the fecalith, drainage of the abscess and antibiotical therapy all patients attained definitive healing. An appendicolith can escape into the abdominal cavity before or during appendectomy, causing complications. An unrecognised fecalith is a rare cause for intraabdominal abscess formation. Nevertheless in patients with an intraabdominal abscess after appendectomy a thorough radiological search for a fecalith by means of plain abdominal radiograph and abdominal ultrasound is mandatory. Surgical removal of the intraabdominal fecalith is the only way to definitive healing.

Abdominal Abscess↗
PubMed2000

Import of a cytosolic protein into lysosomes by chaperone-mediated autophagy depends on its folding state.

We have analyzed the folding state of cytosolic proteins imported in vitro into lysosomes, using an approach originally developed by Eilers and Schatz, (Eilers, M., and Schatz, G. (1986) Nature 322, 228-232) to investigate protein import into mitochondria. The susceptibility toward proteases of mouse dihydrofolate reductase (DHFR), synthesized in a coupled transcription-translation system with rabbit reticulocytes, decreased in the presence of its substrate analogue, methotrexate. This analogue complexes with high affinity with the in vitro synthesized DHFR and locks it into a protease-resistant folded conformation. DHFR was taken up by freshly isolated rat liver lysosomes and methotrexate reduced this uptake by about 80%. A chimeric DHFR protein, which carries the N-terminal presequence of subunit 9 of ATP synthase preprotein from Neurospora crassa fused to its N terminus, was taken up by lysosomes more efficiently. Again, methotrexate abolished the lysosomal uptake of the fusion protein, which was partially restored by washing of methotrexate from DHFR or by adding together methotrexate and dihydrofolate, the natural substrate of DHFR. Immunoblot analysis with anti-DHFR of liver lysosomes and of other fractions, isolated from rats starved for 88 h and treated with lysosomal inhibitors, suggests that DHFR is degraded by chaperone-mediated autophagy. Competition with ribonuclease A and stimulation by ATP/Mg(2+) and the heat shock cognate protein of 73 kDa show that the lysosomal uptake of the fusion protein also occurs by this pathway. It is concluded that the lysosomal uptake of cytosolic proteins by chaperone-mediated autophagy mainly occurs by passage of the unfolded proteins through the lysosomal membrane. Therefore, this mechanism is different from protein transport into peroxisomes, but similar to the import of proteins into the endoplasmic reticulum and mitochondria.

Animals↗
PubMed2000

Cytosolic Hsp70s are involved in the transport of aminopeptidase 1 from the cytoplasm into the vacuole.

Eukaryotic 70 kDa heat shock proteins (Hsp70s) are localized in various cellular compartments and exhibit functions such as protein translocation across membranes, protein folding and assembly. Here we demonstrate that the constitutively expressed members of the yeast cytoplasmic Ssa subfamily, Ssa1/2p, are involved in the transport of the vacuolar hydrolase aminopeptidase 1 from the cytoplasm into the vacuole. The Ssap family members displayed overlapping functions in the transport of aminopeptidase 1. In SSAI and SSAII deletion mutants the precursor of aminopeptidase 1 accumulated in a dodecameric complex that is packaged in prevacuolar transport vesicles. Ssa1/2p was prominently localized to the vacuolar membrane, consistent with the role we propose for Ssa proteins in the fusion of transport vesicles with the vacuolar membrane.

Adenosine Triphosphatases↗
PubMed2000

Cardiac surgery in patients with end-stage renal disease: 10-year experience.

BACKGROUND: End-stage renal disease is known to be an important risk factor complex for cardiac operations performed with cardiopulmonary bypass. METHODS: To investigate the influence of preoperative status on perioperative mortality and morbidity, we retrospectively analyzed data from 65 patients (20 women and 45 men with a mean age of 58.8+/-10.0 years [+/-standard deviation]) with end-stage renal disease who were on dialysis and who underwent a cardiac surgical procedure between 1988 and 1998. RESULTS: Fifty-one percent of the patients had isolated coronary artery bypass grafting, 35% had replacement or reconstruction of one valve or two valves, and 14% underwent combined coronary artery bypass grafting and valve replacement. The perioperative mortality rate was 13.8% with 78% (7 of 9) of deaths occurring in patients having a valve procedure. Six of the 9 patients who died had compromised left ventricular function preoperatively, and all 9 were in New York Heart Association class III or IV. Mean preoperative duration of dialysis was longer (80+/-70 months) in the 9 patients who died compared with that in the surviving 56 patients (45+/-49 months) (p = 0.05). We found dyspnea at rest, duration of dialysis of 60 months or more, combined procedures (coronary artery bypass grafting and valve operation), and New York Heart Association class IV to be associated with a higher relative risk for perioperative death. Neither angina pectoris nor isolated coronary artery bypass grafting was associated with increased relative risk for perioperative death. However, after a cardiac operation, mortality in patients with end-stage renal disease was substantially higher than in those with normal renal function. CONCLUSIONS: These data are comparable with those in the literature and possibly suggest that both indications and referral for surgical intervention have been delayed in patients who have end-stage renal disease combined with coronary artery disease, valve disease, or both. The delay may contribute to the relatively high perioperative mortality.

Adult↗
PubMed2000

Surgical repair of right-atrial aneurysm.

Atrial fibrillation and embolic events are the most common clinical symptoms of congenital right- or left-atrial aneurysms. We report an a case of righ-atrial aneurysm, in a patient with typical history of atrial fibrillation and history of stroke. The aneurysm was resected, but the patient suffered from acute embolic occlusion of the left anterior descending coronary artery on the fourth postoperative day despite of systemic heparinization with 300 IU/kg bw per 24 hours.

Anticoagulants↗
PubMed2000

Critical care medicine education of surgeons: recommendations from the Surgical Section of the Society of Critical Care Medicine.

PERSPECTIVE: The role of surgeons in critical care medicine has a long and esteemed past. The presence of surgeons in intensive care units provides specific insights and perspectives to the care of surgical patients sometimes not fully appreciated by the non-surgical practitioners caring for the same patients. The training and education of surgeons is becoming more complex, fragmented, and lengthy. The knowledge base and skill set required to manage critically ill or injured surgical patients is also becoming more extensive but has the potential of becoming lost in the process of providing the overall educational program for surgical trainees. Simultaneously, nonsurgical specialties are continuing to train individuals with special skills in critical care medicine and the concept of "hospitalists" is becoming more accepted by institutions across the United States. The certification exams in critical care medicine remain under the aegis of the individual medical specialty boards, and there is still not a unified examination process in critical care. Surgeons, in particular, have tremendous pressures these days to spend more clinical time in the operating room, and the task of consistently conducting high quality research is also becoming arduous. This list of reasons could continue but are simply examples for why surgeons need to spend focused attention on how best to train and educate upcoming surgical trainees in regards to the principles of critical care medicine. The critically ill or injured patients need this focused attention and the specialty of surgical critical care medicine needs this attention. The Surgical Section of the Society of Critical Care Medicine has developed this position statement in the hopes that ongoing discussion and refinement of this particular aspect of surgery will continue on several levels.

Critical Care↗
PubMed1999

Domain structure and lipid interaction of recombinant yeast Tim44.

Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane. It functions as a membrane anchor for the ATP-driven protein import motor whose other subunits are the mitochondrial 70-kDa heat-shock protein (mhsp70) and its nucleotide exchange factor, mGrpE. To understand how this motor is anchored to the inner membrane, we have overexpressed Tim44 in Escherichia coli and studied the properties of the pure protein and its interaction with model lipid membranes. Limited proteolysis and analytical ultracentrifugation indicate that Tim44 is an elongated monomer with a stably folded C-terminal domain. The protein binds strongly to liposomes composed of phosphatidylcholine and cardiolipin but only weakly to liposomes containing phosphatidylcholine alone. Studies with phospholipid monolayers suggest that Tim44 binds to phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region.

Cardiolipins↗
PubMed1999

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.

Adrenergic beta-Antagonists↗
PubMed1999

Simultaneous carotid and coronary artery surgery: indications and perioperative outcome.

BACKGROUND: A significant number of patients with coronary artery disease is diagnosed with additional carotid artery disease. This subset of patients has been identified as a high-risk group for cardiac and cerebral complications following surgical intervention. METHODS: In a retrospective analysis we investigated the perioperative outcome of combined single-stage carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in 63 patients operated between January 1989 and August 1998. In all of these patients, CEA was performed prior to CABG and before initiation of cardiopulmonary bypass. RESULTS: Perioperative mortality rate was 7.9% (5/63) for simultaneous CEA and CABG and was due to cardiac complications in all patients. Postoperative unilateral neurological symptoms were diagnosed in 1 patient (1.7%) and were completely reversible. No neurologic events suggestive for permanent cerebral damage were observed during the 30 d postoperative period. CONCLUSIONS: In our study combined single-stage CEA and CABG was associated with low cerebral morbidity and patient outcome was mainly determined by cardiac complications. In this subset of patients, simultaneous CEA and CABG appears to be a safe method.

Carotid Stenosis↗
PubMed1999

Import into and degradation of cytosolic proteins by isolated yeast vacuoles.

In eukaryotic cells, both lysosomal and nonlysosomal pathways are involved in degradation of cytosolic proteins. The physiological condition of the cell often determines the degradation pathway of a specific protein. In this article, we show that cytosolic proteins can be taken up and degraded by isolated Saccharomyces cerevisiae vacuoles. After starvation of the cells, protein uptake increases. Uptake and degradation are temperature dependent and show biphasic kinetics. Vacuolar protein import is dependent on cytosolic heat shock proteins of the hsp70 family and on protease-sensitive component(s) on the outer surface of vacuoles. Degradation of the imported cytosolic proteins depends on a functional vacuolar ATPase. We show that the cytosolic isoform of yeast glyceraldehyde-3-phosphate dehydrogenase is degraded via this pathway. This import and degradation pathway is reminiscent of the protein transport pathway from the cytosol to lysosomes of mammalian cells.

Biological Transport↗
PubMed1998

Mitochondrial Hsp70 cannot replace BiP in driving protein translocation into the yeast endoplasmic reticulum.

To determine whether mitochondrial hsp70 (mHsp70) could substitute for the endoplasmic retuculum (ER) Hsp70 (BiP) during protein translocation, we assembled ER-derived reconstituted proteoliposomes supplemented with either protein. We found that only BiP restored translocation in kar2 mutant vesicles and stimulated translocation approximately 3-fold in wild type proteoliposomes. mHsp70 associated poorly with both a BiP binding (DnaJ) domain of Sec63p and an ER precursor, and its ATPase activity was poorly enhanced upon incubation with the DnaJ domain. In contrast, BiP bound to the Sec63p-DnaJ domain in an ATP-dependent manner and its ATPase activity was stimulated significantly by this polypeptide. We conclude that mHsp70 is unable to support protein translocation into the ER because it fails to associate productively with Sec63p and a precursor.

Endoplasmic Reticulum↗
PubMed1998

Significance of exercise-induced ST-segment elevation and T-wave pseudonormalization for improvement of function in healed Q-wave myocardial infarction.

Exercise-induced ST-segment elevation and pseudonormalization of negative T waves (ST-T segment changes) in infarct leads indicate myocardial viability after Q-wave myocardial infarcts in some patients and may therefore identify patients who will benefit from revascularization. Global left ventricular ejection fraction and wall motion abnormalities of the left ventricle were analyzed in 34 patients with healed myocardial infarction (11 patients with ST-segment elevation, 3 patients with pseudonormalization of the negative T wave (group 1), and in 20 patients without ST-T segment changes during an exercise electrocardiogram (group 2)) before and 4 months after successful revascularization. Wall motion abnormality in the central infarct region at baseline was similar in both groups (-3.1 +/- 0.6 SD vs 3.0 +/- 0.8 SD; NS). At repeat angiography, wall motion abnormality improved significantly from -3.1 +/- 0.6 SD to -2.1 +/- 0.6 SD (p <0.01) in group 1 and was unchanged in group 2 (-3.0 +/- 0.8 SD vs -2.9 +/- 0.7 SD; NS). Similarly, ejection fraction at control angiography had increased from 54 +/- 14% to 66 +/- 12% (p <0.01) in group 1, but decreased from 56 +/- 9% to 55 +/- 9% in group 2 (NS). Exercise-induced ST-T segment changes yielded a sensitivity of 80% and a specificity of 89% to predict significant improvement of the left ventricular ejection fraction. Exercise-induced changes of the ST-T segment identify patients with a high probability of improvement of myocardial function after revascularization in patients with healed myocardial infarcts.

Adult↗
PubMed1998

Significance of rest technetium-99m sestamibi imaging for the prediction of improvement of left ventricular dysfunction after Q wave myocardial infarction: importance of infarct location adjusted thresholds.

OBJECTIVE: The value of rest technetium-99m (Tc-99m) sestamibi scintigraphy under oral nitrate medication to predict myocardial viability was examined in patients with chronic infarcts. BACKGROUND: The value of rest Tc-99m sestamibi to predict viability in infarct regions has not been fully established because significant underestimation of viability, especially in the inferior myocardial wall, has been reported. METHODS: Forty patients with Q wave myocardial infarction underwent Tc-99m sestamibi single-photon emission computed tomography under nitrate medication before revascularization of the infarct-related artery. Wall motion was quantified from paired angiograms before and 4 months after revascularization. Tracer uptake was quantified in the central infarct region identified on the angiogram. RESULTS: The average Tc-99m sestamibi uptake in the central infarct region of patients with anterior infarcts and improvement of left ventricular function was significantly higher (68+/-12%, mean+/-SD) than in patients without improvement of function (40+/-14%, p < 0.02). The average Tc-99m sestamibi uptake in the central infarct region of patients with improvement of function and inferior infarcts was significantly lower (43+/-7%) than in patients with anterior infarcts (68+/-12%, p < 0.003), but was significantly higher than in patients with inferior infarction and no improvement of function (31+/-7%, p < 0.02). Using an infarct location adjusted optimal threshold (50% for anterior infarcts, 35% for inferior infarcts), Tc-99m sestamibi had a positive predictive value of 90% and a negative predictive value of 91% for improvement of left ventricular function. CONCLUSION: Quantitative rest Tc-99m sestamibi scintigraphy after oral nitrates reliably predicts improvement of left ventricular function after revascularization if infarct location adjusted thresholds are used.

Aged↗
PubMed1998

Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated. METHODS: Eighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET), respectively. RESULTS: Intraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (P<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMR Glc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (r= -0.46, P<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc. CONCLUSIONS: HITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage.

Adult↗
PubMed1998

Economic evaluation of desirudin vs heparin in deep vein thrombosis prevention after hip replacement surgery.

Deep vein thrombosis is a serious complication of orthopaedic surgery and can lead to pulmonary embolism and long term post-thrombotic syndrome. A simulation model based on both epidemiological data and data from clinical trials was used to compare the long term cost effectiveness of standard prophylaxis with subcutaneous unfractionated heparin with that of desirudin (recombinant hirudin), in patients undergoing elective hip replacement. The analysis, which was performed before the price of desirudin was set, showed that prophylactic treatment with desirudin saved 4.5 life-years per 100 patients treated, compared with unfractionated heparin. Desirudin prophylaxis was dominant up to a total drug cost of 4400 Swedish kronor (SEK) per treatment. The results were robust against changes in the parameters used in several sensitivity analyses. This study showed that prophylactic therapy with desirudin compared with unfractionated heparin was more cost effective and potentially cost saving under a wide range of assumptions concerning the future price of desirudin in preventing deep vein thrombosis following elective hip surgery.

Anticoagulants↗
PubMed1997

QT dispersion is determined by the extent of viable myocardium in patients with chronic Q-wave myocardial infarction.

BACKGROUND: QT dispersion is lower in patients with successful thrombolysis after acute myocardial infarction, suggesting that QT dispersion may be determined by the extent of viable and scarred myocardium. METHODS AND RESULTS: To test this hypothesis, QT dispersion was measured in a 12-lead resting ECG in 44 patients with chronic Q-wave myocardial infarction. To assess the extent of viable and scarred myocardium, all patients underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). In addition, all patients had revascularization of the infarct-related artery and repeated angiography 4 months later. QT dispersion was lower (53+/-20 versus 94+/-24 ms, P<.0001) in patients with evidence of a substantial amount of viable myocardium in the infarct region as demonstrated by PET (average FDG uptake > or = 50% of normalized, maximum FDG uptake) than in patients with only minimal residual viability. Average FDG uptake of the infarct region and FDG defect size were significantly related to QT dispersion (r=.64, P<.0001; r=.67, P<.0001), whereas ejection fraction was not (r<.1, P=NS). QT dispersion of < or = 70 ms had a sensitivity of 85% and a specificity of 82% to predict viable myocardium in the infarct region. QT dispersion was also lower in patients with improvement of left ventricular function 4 months after revascularization (54+/-21 versus 88+/-30 ms, P=.0003). QT dispersion of < or = 70 ms had a sensitivity of 83% and a specificity of 71% to predict improvement of left ventricular function. CONCLUSIONS: QT dispersion is determined by the amount of viable myocardium in the infarct region and may serve as a novel, rapidly available marker of substantial viability in the infarct region of patients with chronic Q-wave myocardial infarction.

Angioplasty, Balloon, Coronary↗