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Biomedical subjects

U Schmidt

Publications and source records attributed to U Schmidt.

At least 91 records · Page 5Linked to original sources
PubMed2000

Prospective multicenter study of antibiotic prophylaxis in operative treatment of appendicitis.

BACKGROUND/AIMS: A prospective, multicenter observation study was conducted to investigate the effectiveness of antibiotic prophylaxis in the operative treatment of appendicitis. METHODS: Between June 1996 and May 1997, a total of 4,968 patients underwent an operation for appendicitis at 34 East German hospitals. 41.4% (n = 2,424) received perioperative antibiotic prophylaxis whereas in 58.9% of the cases this was not given. The patients who received antibiotic prophylaxis constituted a negative selection, both with regard to risk factors and to the stage of inflammation. RESULTS: In the total test group, the rate for septic disorders of wound healing amounted to 2.5% (n = 120). The use of antibiotic prophylaxis makes it possible to significant lower the incidence of postoperative septic disorders of wound healing (p < 0.001). In both conventional (0.7% with prophylaxis vs. 3.8% without) and in laparoscopic appendectomy (0 vs. 1.0%) the rate for septic disorders of wound healing can be reduced (p < 0.001). The global comparison irrespective of possible antibiotic prophylaxis shows a significant advantage for appendectomies which started with laparoscopy (p = 0.008), but in the subgroups with prophylaxis this advantage is completely neutralized (p = 0.78). CONCLUSION: From this one can deduce that conventional appendectomy with antibiotic prophylaxis comprises no higher risk of wound infection than laparoscopy, since the risk of conversion exists for every operation begun by laparoscopy. These results would lead to the conclusion that antibiotic prophylaxis should be given before every appendectomy, whether by laparoscopy or conventional methods.

Adolescent↗
PubMed2000

Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor receptor messenger RNA.

OBJECT: The goal of this study was to evaluate the activity of certain hairpin ribozymes against deletion-mutant epidermal growth factor receptor (deltaEGFR) messenger (m)RNA in glioblastomas multiforme (GBMs). A distinct 801-bp deletion mutation associated with amplification of the EGFR gene is present in a large subgroup of primary GBMs and confers enhanced tumorigenicity in vivo. As a result of the deletion mutation, the fusion junction of the gene is created directly upstream of a GTA triplet, which is subsequently transcribed into a ribozyme target codon (GUA). METHODS: In attempts to intercept deltaEGFR gene expression at the mRNA level, the authors designed three different hairpin ribozymes derived from the negative strands of satellite RNAs in tobacco ringspot virus, chicory yellow mottle virus (sCYMV1), and arabis mosaic virus against this target and evaluated their efficiency and specificity in a cell-free system. The sCYMV1, identified as the most active anti-deltaEGFR hairpin ribozyme motif, was cloned into the retroviral plasmid N2A+tRNAi(met). High-titer recombinant retrovirus-containing supernatants (> 10(5) colony-forming units/ml) derived from an amphotropic GP+envAM 12 packaging cell line transfected with the N2A+tRNAi(met)-anti-deltaEGFR-sCYMV1 construct were used to introduce the sCYMV1 hairpin ribozyme into U-87MG.deltaEGFR glioblastoma cells, which overexpress exogenous deltaEGFR. Using a virus/target cell ratio of 40:1 in the absence of drug selection, the ribozyme transfer resulted in a greater than 90% reduction of deltaEGFR mRNA levels, a 69% inhibition of deltaEGFR-mediated proliferation advantage, and a greater than 95% decrease of colony formation in soft agar under relative serum starvation conditions in vitro; transfer of a control mutant ribozyme that was rendered incapable of cleaving its target yielded none of these effects. CONCLUSIONS: These findings indicate that the anti-deltaEGFR-sCYMV1 hairpin ribozyme is capable of specifically inhibiting the expression of deltaEGFR and reversing the deltaEGFR-associated malignant phenotype of GBM cells. This strategy may constitute a promising gene therapy approach for a molecularly defined subgroup of GBMs.

Base Sequence↗
PubMed2000

[Interleukin pattern, procalcitonin level and cellular immune status after endovascular aneurysm surgery].

Endovascular repair of AAA's using stent grafts is considered to be a minimally invasive procedure. However, in some cases deleterious inflammatory reactions, e.g., flu-like postinterventional symptoms are observed. A few patients even develop a fatal "postimplantation syndrome". It is not clear whether these postoperative complications result from a) the inflammatory and immune response to the inserted graft material, b) alterations of the vascular endothelium during the implantation procedure, c) residual thrombotic material, or d) a combination of all these causes. This clinical trial aimed to prospectively investigate the association between inflammatory mediators like interleukin-1 receptor antagonist (IL-1RA), IL-6, and HLA-DR expression on monocytes and clinical outcome in patients after repair of abdominal aortic aneurysms (AAA). Fifteen patients treated with endovascular stent grafts for abdominal aortic aneurysm (AAA-E) were compared with 15 selected control patients who underwent a conventional surgical procedure (AAA-K) during the same period. Prior to intervention, there were no significant differences in marker levels. One hour postoperatively, IL-6 (421 pg/ml vs. 21 pg/ml) and IL-1RA (10,061 pg/ml versus 407 pg/ml) were significantly increased in the AAA-K-group, whereas in AAA-E patients, these parameters increased more gradually during the first postoperative day and did not reach the same level as in the control group. There was only a slight reduction of HLA-DR expression in both groups compared with baseline and no signs indicating a postimplantation syndrome were found. No excessive inflammatory response or complicated final outcome were observed. It is unclear if this can be explained by the prophylactic use of indometacin.

Adult↗
PubMed1999

Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a.

BACKGROUND: Failing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca(2+) uptake, and a negative frequency response, which have all been related to a deficiency in the SR Ca(2+) ATPase (SERCA2a) pump. METHODS AND RESULTS: To test the hypothesis that an increase in SERCA2a could improve contractile function in cardiomyocytes, we overexpressed SERCA2a in human ventricular myocytes from 10 patients with end-stage heart failure and examined intracellular Ca(2+) handling and contractile function. Overexpression of SERCA2a resulted in an increase in both protein expression and pump activity and induced a faster contraction velocity (26.7+/-6.7% versus 16.6+/-2.7% shortening per second, P<0.005) and enhanced relaxation velocity (32. 0+/-10.1% versus 15.1+/-2.4%, P<0.005). Diastolic Ca(2+) was decreased in failing cardiomyocytes overexpressing SERCA2a (270+/-26 versus 347+/-30 nmol/L, P<0.005), whereas systolic Ca(2+) was increased (601+/-38 versus 508+/-25 nmol/L, P<0.05). In addition, the frequency response was normalized in cardiomyocytes overexpressing SERCA2a. CONCLUSIONS: These results support the premise that gene-based therapies and targeting of specific pathways in human heart failure may offer a new modality for the treatment of this disease.

Calcium↗
PubMed1999

TGF-beta cooperates with TGF-alpha to induce the self-renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism.

Simultaneous addition of both TGF-alpha and TGF-beta induces the sustained, long-term outgrowth of chicken erythrocytic progenitor cells, referred to as T2ECs from both chick bone marrow and 2-day-old chicken embryos. By analysis for differentiation antigens and gene expression, these cells were shown to represent very immature haematopoietic progenitors committed to the erythrocytic lineage. T2ECs differentiate into almost pure populations of fully mature erythrocytes within 6 days, when TGF-alpha and TGF-beta are withdrawn and the cells exposed to anaemic chicken serum plus insulin. Outgrowth of these cells from various sources invariably required both TGF-alpha and TGF-beta, as well as glucocorticoids. Proliferating, established T2ECs still require TGF-alpha, but are independent of exogenous TGF-beta. Using a TGF-beta-neutralizing antibody or expressing a dominant-negative TGF-beta receptor II, we demonstrate that T2ECs generate an autocrine loop involving TGF-beta during their establishment, which is required for sustained proliferation. Using specific inhibitors, we also show that signalling via Mek-1 is specifically required for induction and maintenance of cell proliferation driven by cooperation between the TGF-alpha and -beta receptors. These results establish a novel mechanism by which self-renewal of erythrocytic progenitors is induced and establish avian T2ECs as a new, quasi-optimal model system to study erythrocytic progenitors.

Animals↗
PubMed1999

Chaperone-assisted expression of authentic bovine adrenodoxin reductase in Escherichia coli.

Adrenodoxin reductase is an essential component of the mitochondrial monooxygenase systems that are involved in the synthesis of steroid hormones and related compounds. After removing by mutagenesis a secondary ribosome binding site and an mRNA loop formed between the gene and the vector, large amounts of the enzyme could be produced in Escherichia coli by coexpression with the HSP60-chaperone system. The purified protein was homogeneous enough for reproducible crystallization. The crystals diffracted X-rays isotropically beyond 1.7 A resolution permitting a structure analysis.

Animals↗
PubMed1999

Tracheal lesion caused by percutaneous dilatational tracheostomy--a clinico-pathological study.

OBJECTIVE: To analyse the accuracy of cannula placement and the extent of tracheal lesions of the anterior tracheal wall after percutaneous dilatational tracheostomy (PDT). DESIGN: A clinico-pathological study of tracheal specimens following PDT. SETTING: University hospital. MATERIALS: Forty-two tracheal specimens of intensive care patients (24 male, 18 female; age: 23-70 years) who died unrelated to tracheostomy. INTERVENTIONS: Using tracheoscopic guidance, PDTs were performed by Ciaglia's method. Tracheal cannulas with outer diameters of 11-12 mm were used. The duration of cannulation ranged from 1 to 97 days (median: 10.5 days). RESULTS: PDTs were placed between the 1st and 4th tracheal rings in 32 cases, above the first ring in 7 cases and below the 4th in 3 cases. Twenty specimens showed a horizontal intercartilaginous rupture of the anterior tracheal wall, 12 tracheas additionally had fractures of tracheal rings and in 10 specimens defects of tracheal cartilage (range: 15 mm2-120 mm2) were found. The occurrence of tracheal defects was influenced by the height of puncture (p<0.05) and duration of cannulation (p<0.01). CONCLUSION: Misplacement of the tracheal cannula above or below the intended tracheal area occurred in one-fourth of our patients. The typical tracheal lesion following PDT is transverse rupture of the anterior tracheal wall with or without fracture of neighbouring rings. Extended cartilaginous defects are rare, which may explain the low rate of tracheal stenosis following PDT.

Adult↗
PubMed1999

Outcome and management of blunt liver injuries in multiple trauma patients.

BACKGROUND: In Germany, abdominal trauma in multiple- trauma patients can be observed in about 25-35% of all cases. Due to major bleeding complications, the initial treatment of blunt abdominal trauma in multiple-trauma patients has high priority. The aim of this study was to discuss management, treatment and outcome of blunt liver injury in multiple-trauma patients treated in our department. METHODS: The clinical records of 1192 multiple-trauma patients [injury severity score (ISS) 3-18] treated at the Surgical Department of the University Clinic of Essen from January 1975 to February 1998 were reviewed. Seventy-five patients with an ISS above 18 operated on due to a blunt liver injury could be included. The mean age was 29.82+/-1.80 years (60 males and 15 females). The degree of injury in this group was high (ISS 37.12+/-1.06). RESULTS: Twenty-three of the 75 (30.6%) patients died during their hospital stay. Deceased patients were older (27+/-2 years versus 37+/-4 years; P<0.01) and had a higher ISS (ISS=34.5+/-1 versus 43.2+/-2; P<0.01). In nine cases, death was strongly related to liver injury. Operational blood loss was higher in the group of multiply injured patients with liver injury and in those patients who did not survive (P<0.05). An increased mortality could be seen in this selected patient group when compared with our large collective of multiply injured patients. The age of the patients, the ISS and operative blood loss were the significant factors that influenced the operative mortality after blunt hepatic injuries in our study.

Adult↗
PubMed1999

Engagement and outcome in the treatment of bulimia nervosa: first phase of a sequential design comparing motivation enhancement therapy and cognitive behavioural therapy.

Despite the major advances in the development of treatments for bulimia nervosa, drop-outs and a lack of engagement in treatment, continue to be problems. Recent studies suggest that the transtheoretical model of change may be applicable to bulimia nervosa. The aim of this study was to examine the roles of readiness to change and therapeutic alliance in determining engagement and outcome in the first phase of treatment. One hundred and twenty five consecutive female patients meeting DSM-IV criteria for bulimia nervosa took part in a randomised controlled treatment trial. The first phase of the sequential treatment compared four sessions of either cognitive behavioural therapy (CBT) or motivational enhancement therapy (MET) in engaging patients in treatment and reducing symptoms. Patients in the action stage showed greater improvement in symptoms of binge eating than did patients in the contemplation stage. Higher pretreatment scores on action were also related to the development of a better therapeutic alliance (as perceived by patients) after four weeks. However, pretreatment stage of change did not predict who dropped out of treatment. There were no differences between MET and CBT in terms of reducing bulimic symptoms or in terms of developing a therapeutic alliance or increasing readiness to change. The results suggest that the transtheoretical model of change may have some validity in the treatment of bulimia nervosa although current measures of readiness to change may require modification. Overall, readiness to change is more strongly related to improvement and the development of a therapeutic alliance than the specific type of treatment.

Adult↗
PubMed1999

Manual-assisted cognitive-behaviour therapy (MACT): a randomized controlled trial of a brief intervention with bibliotherapy in the treatment of recurrent deliberate self-harm.

BACKGROUND: The treatment of deliberate self-harm (parasuicide) remains limited in efficacy. Despite a range of psychosocial, educational and pharmacological interventions only one approach, dialectical behaviour therapy, a form of cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but this is lengthy and intensive and difficult to extrapolate to busy clinical practice. We investigated the effectiveness of a new manual-based treatment varying from bibliotherapy (six self-help booklets) alone to six sessions of cognitive therapy linked to the booklets, which contained elements of dialectical behaviour therapy. METHODS: Thirty-four patients, aged between 16 and 50, seen after an episode of deliberate self-harm, with personality disturbance within the flamboyant cluster and a previous parasuicide episode within the past 12 months, were randomly assigned to treatment with manual-assisted cognitive-behaviour therapy (MACT N = 18) or treatment as usual (TAU N = 16). Assessment of clinical symptoms and social function were made at baseline and repeated by an independent assessor masked to treatment allocation at 6 months. The number and rate of all parasuicide attempts, time to next episode and costs of care were also determined. RESULTS: Thirty-two patients (18 MACT; 14 TAU) were seen at follow-up and 10 patients in each group (56% MACT and 71% TAU) had a suicidal act during the 6 months. The rate of suicidal acts per month was lower with MACT (median 0.17/month MACT; 0.37/month TAU; P = 0.11) and self-rated depressive symptoms also improved (P = 0.03). The treatment involved a mean of 2.7 sessions and the observed average cost of care was 46% less with MACT (P = 0.22). CONCLUSIONS: Although limited by the small sample, the results of this pilot study suggest that this new form of cognitive-behaviour therapy is promising in its efficacy and feasible in clinical practice.

Adolescent↗
PubMed1999

Synthesis and cytostatic activities of didemnin derivatives.

The highly cytostatic didemnins contain a 23-membered cyclopeptolide with a side chain attached to the backbone through the amine group of threonine. Thirty-six derivatives varying the side chain were prepared, but only compounds with D-MeLeu attached to threonine show remarkable biological activities. To protect the macrocycle from degradation by lipases the two ester bonds were replaced successively by amide bonds. Although these variations have a major effect on the conformation and rigidity of the ring, the compound which contains exclusively amide bonds is highly active, equivalent to acetyl-didemnin A.

Antineoplastic Agents↗
PubMed1999

CpG-DNA upregulates the major acute-phase proteins SAA and SAP.

The acute-phase response is an immediate reaction of the host against invading microorganisms. We show here that oligodeoxynucleotides (ODNs) containing a CpG motif rapidly induce the major murine acute-phase proteins in vivo, i.e. serum amyloid A (SAA) and serum amyloid P (SAP). Serum levels of these proteins are elevated within 12 h and peak at 24 h after the injection of CpG-ODN or endotoxin. Liver cells produce the proteins with the same kinetics. Injection of interleukin 6 (IL-6), IL-1beta and tumour necrosis factor alpha (TNF-alpha) induces SAA and SAP in vivo, but the CpG-ODN-mediated induction does not depend on the presence of the TNF receptor p55, as the acute-phase response in TNF receptor p55-deficient mice does not differ from that of wild-type mice. Aside from CpG-ODN, bacterial genomic DNA also induces the acute-phase response in LPS-resistant C3H/Hej mice. The induction of the major acute-phase proteins SAA and SAP is blocked by the simultaneous injection of CpG-ODN together with D-galactosamine (D-GalN). As D-GalN sensitizes the host for the toxic effects of TNF-alpha, a possible mechanism could be the prevention of synthesis of the major acute-phase proteins SAA and SAP.

Acute-Phase Reaction↗
PubMed1999

Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine.

In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.

Aged↗
PubMed1999

The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers.

A randomised, controlled, double-blind trial was performed on 102 male and female volunteers to determine whether reaction time, alertness and concentration might be impaired by treatment with a native valerian root extract (VRE). The effect was first examined the morning after a single evening dose of VRE (600 mg LI 156) vs. flunitrazepam (FNZ) (1 mg) and placebo (PL) (trial section A), and then after two weeks of evening administration of VRE (600 mg LI 156) vs. PL (trial section B). 99 volunteers were analysed in section A and 91 in section B. The primary criterion was the median of reaction time (MRT) measured with the Vienna Determination Test. Secondary criteria were cognitrones (alertness test), tracking test (two-handed co-ordination), sleep quality (VIS-A, Vis-M), further VDT parameters, and safety criteria. The single administration of LI 156 did not impair the reaction abilities, concentration and co-ordination. After 14 days of treatment, the equivalence of VRE and PL was proven by confirmative analysis concerning the improvement of MRT (p = 0.4481). Evaluation of the secondary criteria were consistent with the results of the primary criterion. It is concluded that neither single nor repeated evening administrations of 600 mg of VRE have a relevant negative impact on reaction time, alertness and concentration the morning after intake.

Adult↗
PubMed1999

Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin.

OBJECTIVE: To assess the effect of a combined antithrombin III and C1-esterase inhibitor treatment on intravascular organ fibrin deposition and cardiorespiratory changes following intravenous Escherichia coli endotoxin (lipopolysaccharide [LPS] 80 microg/kg i.v.) exposure. DESIGN: Prospective, randomized trial. SETTING: Research laboratory of a university medical center. SUBJECTS: Anesthetized, instrumented and mechanically ventilated rabbits ([Chbb:CH); n = 40). INTERVENTIONS: Endotoxin was given to 30 animals. Ten animals received no inhibitor (endotoxin control group). The other animals were either treated by high-dose (300 units/kg; n = 10) or low-dose (100 units/kg; n = 10) combined antithrombin III and C1-esterase inhibitor administration. Ten rabbits (time control group) were given placebo (sodium chloride 0.9%). Cardiorespiratory variables were assessed at baseline, 120 mins, and 240 mins after endotoxin or placebo administration. Four hours after endotoxin injection, liver, lung, and kidney tissue samples were examined for intravascular fibrin deposition by light microscopy. MEASUREMENTS AND MAIN RESULTS: Inhibitor treatment significantly decreased clot formation in lungs and livers without, however, demonstrating a clear dose-dependent effect. Combined antithrombin III/C1-esterase treatment attenuated the decrease of mean arterial pressure and cardiac output observed following endotoxin injection. Blood pressure improvement was significantly dependent on dosage administered. CONCLUSION: Combination of antithrombin III and C1-esterase inhibitor treatment during early endotoxin shock decreased organ fibrin deposition and improved cardiovascular stability.

Animals↗