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Biomedical subjects

S Wilhelm

Publications and source records attributed to S Wilhelm.

At least 91 records · Page 5Linked to original sources

Comparison of continuous spinal with combined spinal-epidural anesthesia using plain bupivacaine 0.5% in trauma patients.

We investigated the efficacy and complications of microcatheter spinal anesthesia (CSA) in comparison to a combined spinal-epidural technique (CSE) using plain bupivacaine 0.5%. Sixty trauma patients randomly received either CSA using a 22-gauge Sprotte needle and a 28-gauge microcatheter or CSE after insertion of a 22-gauge epidural catheter through an 18-gauge Tuohy needle followed by dural puncture with a 25-gauge pencil-point needle inserted through the backeye of the Tuohy needle. An initial subarachnoid bolus of 2 mL of plain bupivacaine 0.5% was injected. If analgesia did not reach T12 within 20 min, supplemental bupivacaine was injected either intrathecally or epidurally up to a maximum of 5 mL in the CSA group or 16 mL in the CSE group. Mean arterial blood pressure, heart rate, and analgesic levels were recorded. On postoperative Day 4, patients were interviewed for postanesthetic complaints. Technical problems were more frequent in the CSE group than in the CSA group (47% vs 13%). Performance of anesthesia was faster (8 +/- 3 vs 15 +/- 8 min) and the total dose of bupivacaine lower (3.2 +/- 1.0 vs 9.7 +/- 5 mL) in patients who received CSA. The incidence of hypotension did not differ significantly. However, more patients in the CSE group were treated for bradycardia (4 vs 0). The number of patients suffering from postdural puncture headache was comparable in both groups, but there were more patients with lower back pain in the CSE group (8 vs 2). In conclusion, our data suggest that microcatheter CSA is not associated with an increased rate of complication in patients with lower limb fractures.

Adult↗

Autobiographical memory in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) (N = 36) and healthy controls (N = 24) participated in an autobiographical memory experiment in which they were asked to retrieve specific personal memories in response to cue words having either positive (e.g. happy) or negative (e.g. anxiety) valence. Compared to control participants, OCD patients had difficulty retrieving specific memories and showed longer retrieval latencies. However, these overgenerality effects were not a function of OCD per se, but were related to a co-morbid diagnosis of major depression. The difficulty in retrieving specific autobiographical memories exhibited by OCD patients might reflect excessive cognitive capacity consumption due to pre-occupation with intrusive thoughts typical of major depression.

Adult↗

Requirements for proteolysis during apoptosis.

The key effector proteins of apoptosis are a family of cysteine proteases termed caspases. Following activation of caspases, biochemical events occur that lead to DNA degradation and the characteristic morphological changes associated with apoptosis. Here we show that cytoplasmic extracts activated in vitro by proteinase K were able to cleave the caspase substrate DEVD-7-amino-4-methylcoumarin, while neither proteinase K nor nonactivated extracts were able to do so alone. Caspase-like activity was inhibited by the specific caspase inhibitor DEVD-aldehyde and by the protease inhibitor iodoacetamide, but not by N-ethylmaleimide. When added to isolated nuclei, the activated extracts caused internucleosomal DNA degradation and morphological changes typical of apoptosis. As DNA cleavage and morphological changes could be inhibited by N-ethylmaleimide but not by iodoacetamide, we conclude that during apoptosis, caspase activation causes activation of another cytoplasmic enzyme that can be inhibited by N-ethylmaleimide. Activity of this enzyme is necessary for activation of endonucleases, DNA cleavage, and changes in nuclear morphology.

Animals↗

Complete amino acid sequence of the A chain of mistletoe lectin I.

The complete amino acid sequence of the A chain of mistletoe lectin I was determined via Edman degradation sequencing of the N-terminus and tryptic and endoproteinase Asp-N overlapping fragments, amino acid analysis and MALDI-MS. The data obtained show a great homology with the chains of ribosome-inactivating proteins such as ricin and abrin with 111 (abrin-a) and 103 (ricin-D) amino acid residues conserved, respectively. The knowledge of the primary structure of MLA will have a fundamental impact on elucidating the biological function of medically applied mistletoe lectins on a molecular basis.

Amino Acid Sequence↗

Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs.

PURPOSE: This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model. METHODS: Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g.dl-1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 mu needle probe. RESULTS: In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 +/- 8%, P < 0.01) at the end of transfusion than in Group 1 (37 +/- 13%) and 2 (32 +/- 5%). In Group 3, mean tissue oxygen tension increased from 16 +/- 5 mmHg after haemodilution to 56 +/- 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 +/- 9, P < 0.01) and Group 2 (29 +/- 11, P < 0.01). While in Group 3 an augmentation of 0.7 g.dl-1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g.dl-1 and 2.1 g.dl-1 were needed in Groups 1 and 2 to reach this level (P < 0.01). CONCLUSION: The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.

Animals↗

Directed forgetting in obsessive-compulsive disorder.

We tested whether patients with obsessive-compulsive disorder (OCD) are characterized by dysfunction in the ability to forget disturbing material. Employing a directed forgetting procedure, we presented OCD patients and healthy control subjects with a series of negative, positive, and neutral words, and instructed them either to remember or to forget each item after it was presented. Subjects received free recall and recognition tests for all words, regardless of instructions. Orthogonal planned contrasts indicated that OCD patients exhibited deficits in the ability to forget negative material relative to positive and neutral material, whereas control subjects did not. Additional analyses suggested that OCD patients elaboratively encoded negative words, regardless of instructions, thereby enhancing their memorability.

Adult↗

[Does propofol have advantages over isoflurane for sufentanil supplemented anesthesia in children for strabismus surgery?].

OBJECTIVE: The present study investigates the effectivity and the incidence of side effects of sufentanil-supplemented propofol versus isoflurane anaesthesia in children undergoing elective strabismus surgery. METHODS: 130 children (aged 3-11; ASA I-II) were randomly allocated to one of four groups. In group 1 and 2, anaesthesia was induced with 2 mg/kg propofol and maintained with 15-20 mg/kg x h propofol and 30% O2 in air (group 1) or 10-15 mg/kg x h propofol in N2O (group 2). After induction with either 2 mg/kg propofol (group 3) or 5 mg/kg thiopentone (group 4), anaesthesia was maintained with 0.8-1.5 Vol% isoflurane and N2O in 30% O2 in these groups. All children were orally premedicated with midazolam and atropine and received a single dose of intravenous sufentanil (0.5 micrograms/kg) and atracurium (0.5 mg/kg) prior to intubation. Heart rate, mean arterial blood pressure and pulse oximetry were registered 5 min prior and after intubation as well as 10 min before and 5 min after extubation. The incidence of pain and involuntary movements during injection, oculocardiac reflex (OCR), laryngospasm and postoperative shivering were as well registered as the duration of the operation and the time of extubation. Episodes of nausea and vomiting were documented during 24 hours postoperatively. RESULTS: TIVA with Propofol resulted in a decreased heart rate (p = 0.002) and a higher frequency of OCR (p = 0.01) than thiopentone/isoflurane anaesthesia with a higher sensitivity of children younger than 6 years (p = 0.007) in all groups. There were no differences in extubation time between groups. The overall incidence of nausea (p = 0.002) and vomiting (p = 0.007) was lower in group 1 and 2 when compared to group 3 and 4. CONCLUSION: Propofol as an induction agent of balanced anaesthesia fails to show advantages over thiopentone. During total intravenous anaesthesia propofol increases the risk of bradycardia especially in younger children. However, a significantly lower incidence of postoperative nausea and vomiting after TIVA with propofol and sufentanil, irrespective of N2O administration, may be an advantage over isoflurane anaesthesia in paediatric patients after strabismus surgery.

Anesthesia, General↗

Propofol reduces emesis after sufentanil supplemented anaesthesia in paediatric squint surgery.

BACKGROUND: Squint surgery is associated with a high incidence of postoperative emesis. The purpose of this prospective study was to examine the influence of propofol and isoflurane anaesthesia on the incidence of postoperative nausea and vomiting in children. METHODS: Ninety children aged 3-10 years were randomly allocated to one of 3 groups. In all groups, children received 2 mg/kg propofol, 0.5 microgram/kg sufentanil and 0.5 mg/kg atracurium for induction of anaesthesia. In group 1, anaesthesia was maintained with 15-20 mg/kg.h propofol and children were ventilated with 30% O2 in air. In group 2, anaesthesia was maintained with 10-15 mg/kg.h propofol and 30% O2 in N2O. In group 3, anaesthesia was maintained with 1.0-1.5 Vol% isoflurane and 30% O2 in N2O. The time of extubation, awakening and postoperative surveillance, the incidence and numbers of episodes of postoperative nausea and vomiting were registered as well as requirements of antiemetics. Statistics were made using ANOVA and Chi-square test or Kruskal-Wallis test with P < 0.05 considered as significant. RESULTS: The overall incidence of nausea (P = 0.0001) and vomiting (P = 0.002) was higher in group 3 (70%;73%) than in group 1 (13%;23%) and 2 (20%;28%). Episodes of nausea (P = 0.0001) and vomiting (P = 0.0013) were more frequent in group 3 (74%;69%) than in group 1 (13%;15%) and 2 (13%;16%). Antiemetic requirements were higher and the time of postoperative sleep and surveillance was longer in group 3 than in group 1 and 2 (P = 0.04). CONCLUSION: Propofol-sufentanil anaesthesia results in less emesis and treatment during the early postoperative phase irrespective of N2O administration compared with propofol-induced isoflurane anaesthesia and may be recommended in children undergoing squint surgery.

Anesthesia, Intravenous↗

The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is characterized by a progressive erosion of the articular cartilage. Studies suggest that cytokines and metalloproteases play an important role in this process. Previously, we found that corticosteroids given prophylactically reduce the severity of cartilage lesions. In this study, we examined and compared the in vivo efficacy of a corticosteroid, triamcinolone hexacetonide (TH), administered either prophylactically or therapeutically, on OA lesions and on cartilage metalloproteases, interleukin-1 beta (IL-1 beta), and oncogene synthesis in experimental OA. EXPERIMENTAL DESIGN: This study examines the effect of intraarticular injections of TH on the progression of lesions in the experimental dog model of OA. The animals had the anterior cruciate ligament of the right knee sectioned and were killed 12 weeks after surgery. A total of 30 dogs were used in four groups: group 1 (n = 8) had no treatment; group 2 (n = 8; TH-3) received TH at time of surgery and at 4 and 8 weeks later; group 3 (n = 7; TH-2) received TH at 4 and 8 weeks after surgery; and group 4 (n = 7; TH-1) received TH at 8 weeks after surgery. Knee cartilage was submitted to macroscopic and microscopic examinations, as well as immunohistochemical studies for stromelysin, IL-1 beta, and oncoproteins, c-Fos and c-Myc. RESULTS: Injections with TH significantly reduced the size of osteophytes in dogs from groups TH-3 (p < 0.0001) and TH-2 (p < 0.0002). The histologic severity of cartilage lesions was significantly reduced on condyles in all TH groups and on plateaus of dogs from groups TH-3 and TH-2. Immunohistochemistry revealed that TH significantly reduced the percentage of immunoreactive chondrocytes for stromelysin, and the effect was proportional to the number of injections received. For c-fos and c-myc, the reduction was particularly significant in the TH-3 and TH-2 groups. For IL-1 beta, the reduction was significant only in the TH-3 group. CONCLUSIONS: This study provides novel data showing the protective effect of corticosteroid injections on OA cartilage lesions not only under prophylactic but also under therapeutic conditions. The effect of TH may be mediated through a direct reduction in the expression and synthesis of proteolytic enzymes, such as stromelysin. Alternatively, the steroid could act by inhibiting the stimulation of protease synthesis by cytokines/oncogenes (IL-1 beta, c-Fos, and c-Myc).

Adrenal Cortex Hormones↗

[Measuring the concentration of various plasma and placenta extract proteolytic and vascular factors in pregnant patients with HELLP syndrome, pre-/eclampsia and highly pathologic Doppler flow values].

OBJECTIVE: Impaired trophoblast invasion plays a major role in the development of preeclampsia. Therefore various factors that are involved in invasion were investigated in gestational disease. METHODS: In pregnant women with HELLP-syndrome (n = 18), pre-/eclampsia (n = 21) and highly pathological Doppler flow measurements (hpD) (n = 13), plasma and placental tissue extract concentrations of uPA, uPA-receptor, tPA, PAI-1, MMP-8, MMP-9, TIMP-1, thrombomodulin, and angiogenin were measured using ELISA. RESULTS: In all three collectives, PAI-1 plasma concentrations were significantly higher (p < 0,05) than in normal pregnancies, in patients with HELLP-syndrome, tPA and TIMP-1 plasma levels were also elevated. MMP-9 concentrations in placental tissue extracts were lower in pre-/eclampsia than in normal pregnancies. CONCLUSIONS: Impaired placental implantation and remodelling in gestational disease is reflected by changes in plasma and placental tissue extract concentrations of various factors that are involved in these processes.

Adult↗

Inactivation of receptor-bound pro-urokinase-type plasminogen activator (pro-uPA) by thrombin and thrombin/thrombomodulin complex.

Urokinase-type plasminogen activator (uPA) binds with high affinity to a specific cell surface glycosyl phosphatidyl-inositol (GPI)-anchored receptor, the urokinase receptor (uPAR). Pro-uPA, the enzymatically inactive single-chain form of uPA after having been activated by certain proteases, converts plasminogen into plasmin. This activation of pro-uPA to enzymatically active uPA can be prevented by the action of thrombin on pro-uPA. This inactivation process is accelerated in the presence of thrombomodulin (TM). The present study investigated whether pro-uPA bound to uPAR is still susceptible to inactivation by thrombin in the presence or absence of TM. A truncated soluble form of the uPAR lacking the GPI-anchor was cloned and expressed in CHO-cells (rec-uPAR277). Rec-uPAR277 efficiently inhibited the thrombin-mediated inactivation of pro-uPA up to 90% in a concentration dependent manner. The protective effect of rec-uPAR277 was far less pronounced when thrombin was complexed with TM. Enzyme kinetic experiments with varying concentrations of pro-uPA showed that in the presence of TM the catalytic efficiency (kcat/Km) of thrombin-mediated inactivation raised from 0.010 microM-1 s-1 to 0.50 microM-1 s-1 corresponding to a fifty-fold increase. In the presence of rec-uPAR277, however, the catalytic efficiency dropped by 4.1-fold (0.5 microM-1 s-1 to 0.122 microM-1 s-1). The inactivation kinetics of pro-uPA by thrombin (no TM added) in the presence of an excess of rec-uPAR277 could not be determined since virtually no inactivation occurred. Our data suggest that pro-uPA once bound to uPAR, is significantly protected from inactivation by thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Personality characteristics and serum IgE level in patients with atopic dermatitis.

On the basis of clinical observations it was predicted that patients with atopic dermatitis (AD) differ from patients with chronic obstructive bronchitis (OB) in three personality variables; excitability (EX), inadequate stress coping (CO), and paranoidity (PA). Sixty-one patients with AD and 15 with OB were assessed using standard scales. Systematic comparisons between groups strongly confirmed these hypotheses. It was further assumed that AD patients with clinically relevant serum IgE levels (IgE > 100 IU/ml) score significantly higher on EX and CO than those with normal serum IgE levels (IgE < 100 IU/ml). In contrast, no significant differences between these subgroups were expected regarding paranoidity (which may be a consequence of the AD patients' cosmetic problems). These assumptions again were supported by the findings of the present study. The results underline the potential importance of assessing personality variables and serum IgE levels in the diagnosis of AD patients.

Adaptation, Psychological↗

Semiquantitative determination of IL-1 alpha, TNF-alpha, PDGF-A, PDGF-B, and PDGF-receptor in term human placenta using polymerase chain reaction (PCR).

Eight placenta samples derived from normal term human placenta were examined for the expression levels of Il-1 alpha+, TNF-alpha+, PDGF-A+, PDGF-B+, and PDGF-receptor+ using a semiquantitative PCR protocol. The expressional level of beta-actin was proven to be constant, therefore beta-actin could serve to equilibrate sample size in our procedure. Differences were found in the mRNA levels of IL-1 alpha and TNF-alpha. The expression of PDGF-A, BDGF-B and PDGF-R seemed to be relatively constant in our group of samples. Further investigation and improved quantitative PCR protocols are needed to correlate clinical outcome of pregnancy with cytokine expression at the placental level. +Il-1 alpha (interleukin-1 alpha) +TNF-alpha (tumor necrosis factor-alpha) +PDGF-A (platelet derived growth factor A) +PDGF-B (platelet derived growth factor B) +PDGF-Rezeptor (platelet derived growth factor-rezeptor).

Actins↗

Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study.

Metalloproteases appear to play an important role in the pathophysiology of osteoarthritis (OA) and their expression is believed to be regulated by cytokines such as interleukin-1 (IL-1). Nuclear oncogene products are suggested as mediators through which IL-1 induces metalloprotease gene expression. Little data are available on the in vivo involvement of these agents in the pathophysiology of OA. This study examined by immunohistochemistry, using specific antibodies, the distribution of stromelysin, IL-1 alpha, IL-1 beta, and oncogene products (c-FOS, c-JUN, and c-MYC) in synovium and cartilage from normal and experimental canine models of OA. In the OA synovium, stromelysin and IL-1 were localized in the cytoplasm of superficial synovial lining cells, infiltrating mononuclear cells, and endothelial and smooth muscle cells of the blood vessels, whereas oncoproteins were detected predominantly in the synovial lining cells. Normal synovial membranes demonstrated low levels of specific staining in synovial lining cells with occasional staining of blood vessel cells for IL-1 alpha, IL-1 beta, and stromelysin. In OA cartilage, chondrocytes at the superficial and middle layers as well as in fibrillated areas were found to be involved in the synthesis of stromelysin, IL-1, and oncoproteins. Diffuse staining of stromelysin and IL-1 beta in OA cartilage matrix was also identified. In normal cartilage, only a few chondrocytes at the superficial layer showed a low level of antigens. These results demonstrate the in vivo concomitant cellular and/or matrical presence of stromelysin, IL-1, and oncogene proteins in tissues from experimentally induced OA with the most intense staining at the sites of cartilage erosion and synovial proliferation. These findings suggest that they may be involved in the pathophysiology of OA, and that the regulatory mechanisms involved in the expression of these proteins may be associated.

Animals↗

Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2.

Simian virus 40 (SV40)-transformed human lung fibroblasts secrete both 72-kDa type IV collagenase and a closely related 92-kDa type IV collagenase that was not detected in the parental cell line. The 92-kDa type IV procollagenase purified from these cells exists in a noncovalent complex with the tissue inhibitor of metalloproteases, TIMP. Here we report that the 72-kDa type IV procollagenase purified from HRAS-transformed human bronchial epithelial cells, SV40-transformed lung fibroblasts, and normal skin fibroblasts exists in a stable but noncovalent stoichiometric complex with a 24-kDa inhibitor referred to here as "TIMP-2." TIMP-2 is closely related to TIMP, as demonstrated by comparison of the partial amino acid sequence of this protein to that of TIMP, although it does not cross-react with TIMP-specific antibody. The TIMP-2 inhibitor interacts with the 72-kDa type IV collagenase in preference to the 92-kDa type IV collagenase that forms a complex exclusively with TIMP. The 72-kDa type IV collagenase-TIMP-2 complex can be activated with organomercurials to yield a catalytically competent enzyme. Activation occurs concomitantly with autoproteolytic cleavage of the amino terminus of the protein and does not require dissociation of the complex. Both activity and activation of the complex can be completely inhibited by further addition of stoichiometric quantities of purified TIMP-2 or recombinant TIMP.

Amino Acid Sequence↗

[Portable infusion pump for ambulatory cytostatic therapy in inoperable liver metastases].

Liver metastases were demonstrated in a 48-year-old man 12 years after resection of a carcinoma of the sigmoid colon (pT2, G2, N0, Mx). A computer-driven external infusion pump was implanted and regional liver perfusion instituted with 5-fluoro-uracil. After seven chemotherapy cycles, 4-7 weeks apart, the liver metastases were no longer demonstrable by ultrasound and computed tomography. During the entire course of chemotherapy the patient was able to continue his profession as a teacher without any restriction.

Adenocarcinoma↗