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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed2001

Hypertension as a risk factor for cerebral injury during cardiopulmonary bypass. Protein S100B and transcranial Doppler findings.

We studied 22 patients aged 53-78 years scheduled for cardiac surgery under cardiopulmonary bypass. Blood pressure, cardiac output, transcranial Doppler blood flow velocity, arterial blood gases, body temperature and protein S100B, as a marker for cerebral integrity, were evaluated in normotensive and hypertensive patients. Pre-operative mean (SD) arterial blood pressure was 93 (11) mmHg in the normotensive group compared with 116 (15) mmHg in the hypertensive group. We found an increase in protein S100B levels in both groups. Serum protein S100B concentrations in the hypertensive group were significantly higher than in the normotensive group (p < 0.001). The highest mean (SD) values were 2.04 (0.65) micromol x l(-1) in the normotensive group and 7.02 (4.55) micromol x l(-1) in the hypertensive group. These results suggest that cardiopulmonary bypass is associated with a significantly higher rate of cerebral injury in hypertensive patients than in normotensive patients. This may be due to altered autoregulation and insufficient cerebral perfusion. Modifications of cardiopulmonary bypass management for hypertensive patients might be made to decrease the risk of cerebral injury.

Aged↗
PubMed2001

Cerebral and regional organ perfusion in pigs during xenon anaesthesia.

Little is known about the haemodynamic effects of inhaled xenon on regional organ perfusion. The aim of this study was to investigate the effect of 79% xenon ventilation on organ perfusion in pigs. We investigated 10 pigs, which were randomly allocated to receive either xenon 79% or total intravenous anaesthesia (TIVA)/oxygen anaesthesia. Microspheres were used to determine organ perfusion. The following regions of interest were investigated: cerebral cortex, medulla oblongata, brainstem, cerebellum, liver, kidney, small intestine, colon, muscle, skin and heart. The results demonstrated a significant increase in regional perfusion in the brainstem (+63%), cerebral cortex (+38%), medulla oblongata (+35%) and cerebellum (+34%). All other organs showed no significant change in regional perfusion. We conclude that xenon should be used with caution in clinical situations associated with pathological increases in intracranial pressure, e.g. neurosurgical procedures, head injury, cerebral mass lesions or stroke.

Anesthetics, Combined↗
PubMed2001

Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway.

BACKGROUND & AIMS: Treatment with a chimeric anti-tumor necrosis factor (TNF) antibody (infliximab) has been shown to be highly efficient for patients with steroid-refractory Crohn's disease (CD). However, the mechanism of action remains largely unknown. As monocytopenia is commonly observed after treatment with infliximab, we investigated the role of infliximab-induced monocyte apoptosis. METHODS: Peripheral blood monocytes from healthy volunteers and patients with chronic active CD (CDAI > 250) were isolated by density gradient centrifugation methods. Apoptosis was determined by annexin V staining DNA-laddering, and transmission electron microscopy. Activation of caspases and mitochondrial release of cytochrome C was determined by immunoblotting. Transcriptional activation of members of the Bcl-2 family have been analyzed by ribonuclease protection assay. RESULTS: Treatment with infliximab at therapeutic concentrations resulted in monocyte apoptosis in patients with chronic active CD in a dose-dependent manner. Infliximab-induced monocyte-apoptosis required the activation of members of the caspase-family since activation of caspase-8, -9, and -3 could be determined. Caspase activation was induced by a CD95/CD95L independent signaling pathway with mitochondrial release of cytochrome C. Cytochrome C release seemed to be triggered by transcriptional activation of Bax and Bak. Monocyte apoptosis in vivo as determined by annexin-V binding and caspase-3 activation could be shown in patients with chronic active CD as soon as 4 hours after treatment with infliximab. CONCLUSIONS: Monocyte apoptosis induced by infliximab may be an important mechanism that could explain the powerful anti-inflammatory properties of infliximab in patients with chronic active CD.

Antibodies, Monoclonal↗
PubMed2001

[Liposuction for "body contouring" in gynecology].

OBJECTIVES: The aim of this study was to describe the possible use of the ultrasound-assisted liposuction and liposuction with the tumescent technique for the contouring and remodelling of superficial fat areas of women in the field of gynaecology. PATIENTS AND METHODS: Between 1997 and 1999 85 healthy female patients underwent a liposuction in the department of gynaecology of the university of Essen. The patients were divided into two groups. Thirty patients (group 1) underwent an ultrasound-assisted liposuction whereas the remaining 55 patients (group 2) were operated using only the tumescent technique. RESULTS: From the operated 582 body areas a large volume liposuction with the aspiration of more than 1,000 cc fat was performed in 48.2% of the cases. In the remaining 51.8% of the cases aspiration volumes between 300 and 1,000 cc fat were obtained. No statistically significant differences could be observed when comparing the aspirat volumes between both treatment groups (p > 0.05). Serious complications were not observed. DISCUSSION: Our data could show, that liposuction is an extremely safe method for eliminating surperficial fat depots in the sense of body contouring in gynaecology, but that it should not be used for the reduction of obese body volumes. If ultrasound-assisted liposuction is really superior to liposuction with the tumescent technique remaining uncertain, no time gain could be observed due to this technique.

Adipose Tissue↗
PubMed2001

[Endometrial carcinoma in patients with diabetes mellitus].

OBJECTIVE: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - MATERIAL AND METHODS: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a chi(2)-test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - RESULTS: The mean follow-up period was 49 months. The mean age was 65 years. 21.8 % of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - CONCLUSION: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Aged↗
PubMed2001

[The treatment of a primary acquired melanosis of the conjunctiva with atypia by low dose of Mitomycin C 0.02 % - case report with follow up of 2 years].

BACKGROUND: About 70 % of the melanomas of the conjunctiva develop from an primary acquired melanosis (PAM) with atypia. This is the reason why excision, radiation, cryotherapy or a combination of them are proposed for therapy. But, if the acquired melanosis is very large, serious complications will be found with that treatment. PATIENT AND METHOD: A 65-year-old woman has shown a large melanosis of the conjunctiva of her left eye. Biopsies, taken from different sites of the conjunctiva, have confirmed the diagnosis of an acquired melanosis of the conjunctiva with atypia. This has been the reason for our Mitomycin C 0.02 % therapy for one week. It has been repeated once again after half a year. RESULTS: Atypia of the cells was shown in the upper cell layer of the conjunctiva after the first therapy. But after the second therapy no atypia of the cells was present within two years after the last treatment, examining several biopses. CONCLUSION: Looking for an effective treatment without complications, a new therapy with Mitomycin C has been introduced in the last years. As it is not yet clearly known how to use Mitomycin to have maximal effectiveness with minimal complications, the reports about doses and frequency are differing a lot in the literature and are more often considerably lying over the introduced effective dose of our case. If Mitomycin is used in that low dosage and in that special application as shown, it could be a very efficient therapy with less complications.

Administration, Topical↗
PubMed2001

Muristerone A-induced nerve growth factor release from genetically engineered human dermal fibroblasts for peripheral nerve tissue engineering.

In this study, human dermal fibroblasts (hDFBs) were genetically modified to release human nerve growth factor (NGF) using an ecdysone-inducible system. NGF cDNA was inserted into the pIND vector and then hDFBs were cotransfected with pIND-NGF and pVgRXR. Muristerone A, an analog of ecdysone, was used as the inducing agent. NGF release from transfected hDFBs was assessed in vitro and in vivo. Transfected hDFBs in the presence of Muristerone A possessed a maximal in vitro release of 8.5 +/- 0.4 pg of NGF/mL per 10(3) cells, demonstrating significantly higher NGF levels compared to control hDFBs. The in vitro release rate curve for transfected hDFBs in the presence of Muristerone A exhibited a maximum of 5.1 +/- 0.2 ng NGF/10(6) cells/day. A PC-12 bioassay demonstrated that the in vitro NGF released is bioactive. When transfected hDFBs in the presence of Muristerone A were placed in vivo in nude rats, NGF levels reach 2074 +/- 257 pg/mL and 1620 +/- 132 pg/mL at 24 and 48 h, respectively. These levels were significantly higher than negative control and wound fluid levels. Results support further in vivo investigation of this molecular "on" switch for peripheral nerve regeneration.

Animals↗
PubMed2001

Diffusion of xenon and nitrous oxide into the bowel.

BACKGROUND: Nitrous oxide diffuses easily from blood into air filled spaces. Xenon is also a relatively insoluble gas, like nitrous oxide. Therefore, the authors measured xenon diffusion into obstructed bowel segments during xenon anesthesia and compared this with nitrous oxide and nitrogen diffusion. METHODS: Twenty-one pentobarbital-anesthetized pigs were randomly assigned to three groups to receive either xenon-oxygen, nitrous oxide-oxygen, or nitrogen-oxygen (75%-25%), respectively. In each animal four bowel segments of 15-cm length were isolated. A pressure-measuring catheter was inserted into the lumen, and 30 ml of room air was injected into the segments. Anesthesia with the selected gas mixture was performed for 4 h. Pressure in the segments was measured continuously. The volume of gaseous bowel content was measured on completion of the study. RESULTS: The median volume of bowel gas in animals breathing nitrous oxide was 88.0 ml as compared with 39.0 ml with xenon anesthesia and 21.5 ml in the nitrogen-oxygen group. After 4 h of anesthesia, the intraluminal pressures in the nitrous oxide group were found to be significantly greater than in the control group and in the xenon group. CONCLUSIONS: The amount of diffused gas was significantly lower during xenon anesthesia than with nitrous oxide anesthesia but greater than with controls. Blood solubility can therefore be regarded as an important factor influencing gas diffusion into air filled cavities.

Anesthesia, Inhalation↗
PubMed2001

Dermal fibroblasts genetically engineered to release nerve growth factor.

Current surgical strategies for repair of critical nerves involves the transfer of normal donor nerve from an uninjured body location. One possible alternative to autogenous tissue replacement is the development of engineered constructs to replace those elements necessary for axonal proliferation. Delivery of growth factors is one strategy to enhance synthetic nerve constructs. Thus, this study focused on the delivery of nerve growth factor (NGF) by genetic engineering to begin approaching the microenvironment dictated, in part, by Schwann's cells. Rat dermal fibroblasts (DFBs) were modified genetically to release rat NGF. The reporter gene LacZ was used to assess the optimum nonviral transfection method commercially available before NGF transfection. FuGENE6 provided the optimum transfection efficiency (24% maximum, 20.1 +/- 1.9% 5-day average) as measured by beta-galactosidase catalytic activity. NGF release from transfected DFBs was assessed over a 3-day period. Compared with control (no transfection) DFBs and DFBs transfected with vector alone, DFBs transfected with an expression vector encoding rat beta-NGF demonstrated significantly (p < 0.05) higher levels of NGF, with a 3-day maximum of 111 pg NGF per milliliter. When normalized to cell number, NGF-transfected DFBs released 1.2 pg NGF per milliliter/10(3) cells. The NGF-transfected DFBs demonstrated a maximal NGF release rate at day 1 (1.2 ng NGF/10(6) cells per day), followed by a markedly lower, sustained release rate at days 2 and 3 (0.44 ng NGF/10(6) cells per day and 0.48 ng NGF/10(6) cells per day respectively). The release rate curves for control and vector-transfected DFBs also exhibited a maximal NGF release rate at day 1, but were followed by a decreasing release rate, potentially representing in vitro degradation of NGF present in fetal bovine serum. Although not first with the development of growth factor delivery through fibroblasts, these findings suggest that rat DFBs can be modified genetically to act like Schwann's cells to deliver NGF.

Animals↗
PubMed2001

Deadspace free ventilatory measurements in newborns during mechanical ventilation.

OBJECTIVE: To improve the accuracy of ventilatory measurements in ventilated newborns by means of a numerical correction when a deadspace free differential measuring method using two pneumotachographs (PNTs) is applied and to investigate the clinical usefulness of this correction procedure. DESIGN: In vitro study and prospective animal study. SETTING: Research laboratory of the Clinic of Neonatology and the Animal Research Laboratory, Charité Hospital Berlin. SUBJECTS: Ten newborn piglets, weighing 610-1340 g (median, 930 g), age <12 hrs. INTERVENTIONS: The accuracy of both the deadspace free method and the endotracheal flow measurements (conventional method) was investigated using mechanical lung models. A correction procedure for the deadspace free method was developed considering signal delay time and tube compliance between both PNTs. This method was applied to the piglets measured during partial liquid ventilation (PLV). Measurements were done before and after lung lavage and during 30 and 120 mins of PLV (30 mL/kg body weight perfluorocarbon). MEASUREMENTS AND MAIN RESULTS: In vitro measurements showed volume differences between both methods of 8%, 12%, 16%, and 17%, respectively, depending on the distance between the PNTs of 10, 60, 120, and 180 cm. After applying the correction algorithm, the differences decreased to 3%, 0%, -2%, and -8%, respectively. The piglets were measured with 120-cm tube length between the PNTs. The correction algorithm reduced the measured tidal volume before lavage by 7%, after lavage by 14%, 30-min PLV by 12%, and 120-min PLV by 10%, corresponding to the changes in respiratory compliance of 1.2, 0.6, 1.0, and 1.1 mL/cm H2O. CONCLUSIONS: The deadspace free method can be advantageously used for continuous measurements in newborns despite much higher technical expense. The correcting procedure improved the accuracy of the volume measurement remarkably, especially for lower respiratory compliance.

Algorithms↗
PubMed2001

Prognostic index for cutaneous melanoma: an analysis after follow-up of 2715 patients.

In 2715 of 4524 patients with cutaneous melanoma treated surgically between 1968 and 1992 prognostic parameters were analysed for their value in predicting the occurrence of first progression. All of the 2715 patients developed only one invasive cutaneous melanoma during the follow-up period. Data concerning tumour thickness and mitotic index (maximum number of mitoses per square millimetre) of the cutaneous melanomas were determined. Between the characteristics age, tumour thickness, mitotic index, prognostic index (PI), sex, site of tumour, melanoma subtype and Clark level, the value of the mitotic index, as a prognostic parameter independent of tumour thickness, and the combination of mitotic index and tumour thickness were evaluated. The development of the first metastases was documented during a mean follow-up of 7.5 years. The majority of first recurrences occurred at regional lymph nodes and attempts have been made to identify those patients at risk of developing metastatic disease. The most effective parameters proved to be tumour thickness and mitotic index. For both parameters an independent prognostic influence was shown. The prognostic index, defined as the product of tumour thickness and number of mitoses per square millimetre, was re-evaluated and confirmed. A new modified prognostic index, defined as the product of square tumour thickness and mitotic index, proved to be even more useful for defining a subgroup of patients who are at risk of developing metastases and, therefore, might benefit from adjuvant therapy.

Adult↗
PubMed2001

A model for the detection of clonality in marked hematopoietic stem cells.

The semirandom location of retroviral integration in the target cell genome introduces a marker in the form of a fusion sequence composed of a genomic and a proviral part that is unique for each transduced cell and its clonal progeny. High-sensitivity detection of these fusion sequences would allow the tracking of clonal contributions of individual, marked hematopoietic progenitor, and stem cells in vivo. Clone detection by Southern blot has helped to analyze models of oligoclonal repopulation but is limited in sensitivity and specificity. Inverse PCR (Nolta et al., Proc. Natl. Acad. Sci. USA 93: 2414-2419) can demonstrate the clonal identity by sequencing but does not permit simultaneous detection of multiple clones. In an efficiently transduced rhesus macaque model (Tisdale et al., Blood 92: 2681-2687; Wu et al., Mol. Ther. 1: 285-293) Kim et al. (Blood 96: 1-8) have identified more than 40 insertion sequences from marrow CFU by inverse PCR. However, no previous study has been able to directly analyze the number of clones active in vivo. Here we demonstrate that the application of a recently developed PCR technology allows the simultaneous visualization of multiple integration sites from small clonal contributions to hematopoietic cells. By combining solid-phase primer extension with ligation-mediated PCR, direct genomic sequencing of retroviral integration sites was obtained in murine bone marrow samples. Further development of this technology will allow analysis of the clonal composition of marked hematopoiesis in small and large animals as well as in human gene transfer.

Animals↗
PubMed2001

Differential roles of p21(Waf1) and p27(Kip1) in modulating chemosensitivity and their possible application in drug discovery studies.

In this study, the differential role of the cyclin-dependent kinase (CDK) inhibitors p21(Waf1) and p27(Kip1) in cell cycle regulation was proposed for use in screening natural or synthetic compounds for cell cycle-dependent (particularly M phase-dependent) antineoplastic activity. p21(Waf1) or p27(Kip1) was ectopically expressed with an ecdysone-inducible mammalian expression system in a human colon adenocarcinoma cell line. Induction of p21(Waf1) or p27(Kip1) expression inhibited the activities of CDK2 and completely arrested cells at G(1) phase of the cell cycle by p27(Kip1) and at G(1) and G(2) phases by p21(Waf1). We examined the sensitivity of these cells to several antineoplastic agents known to be cell cycle-dependent or -independent. Substantially increased resistance to cell cycle-dependent antineoplastic agents was found in the cells when the expression of p21(Waf1) or p27(Kip1) was induced. In contrast, only a desensitization to cell cycle-independent antineoplastic agents was found in the cells arrested by p21(Waf1) or p27(Kip1). Because p21(Waf1) induces an additional block at G(2) phase that inhibits cell entry into M phase, we further examined the difference between p21(Waf1)- and p27(Kip1)-induced cells in their sensitivity to D-24851, a novel M phase-dependent compound. We found that induction of p21(Waf1) after exposure of the cells to D-24851 conferred stronger resistance than did induction of p27(Kip1). Taken together, our results suggest that the differential effect of p21(Waf1) and p27(Kip1) on cell cycle regulation may be advantageous for screening chemical libraries for novel antineoplastic candidates that are cell cycle-dependent, and M phase-dependent in particular.

Acetamides↗
PubMed2001

In vitro activities of six quinolones and mechanisms of resistance in Staphylococcus aureus and coagulase-negative staphylococci.

Of 94 clinical isolates of Staphylococcus aureus (n = 51) and coagulase-negative staphylococci (CNS) (n = 43), mutations in the quinolone resistance-determining region of topoisomerases GrlA, GrlB, GyrA, and GyrB together with MICs of six quinolones were analyzed. Amino acid substitutions at identical residues (GrlA residues 80 and 84; GyrA residues 84 and 88) were found in S. aureus and CNS. Active efflux, as suggested by blocking by reserpine, contributed substantially to the resistance phenotype in some strains. Among ciprofloxacin, clinafloxacin, levofloxacin, nalidixic acid, trovafloxacin, and sparfloxacin, a 0.5-microg/ml concentration of sparfloxacin discriminated best between strains with two or three mutations and those with no mutations.

4-Quinolones↗
PubMed2001

Microbial diversity of the brine-seawater interface of the Kebrit Deep, Red Sea, studied via 16S rRNA gene sequences and cultivation methods.

The brine-seawater interface of the Kebrit Deep, northern Red Sea, was investigated for the presence of microorganisms using phylogenetic analysis combined with cultivation methods. Under strictly anaerobic culture conditions, novel halophiles were isolated. The new rod-shaped isolates belong to the halophilic genus Halanaerobium and are the first representatives of the genus obtained from deep-sea, anaerobic brine pools. Within the genus Halanaerobium, they represent new species which grow chemoorganotrophically at NaCl concentrations ranging from 5 to 34%. The cellular fatty acid compositions are consistent with those of other Halanaerobium representatives, showing unusually large amounts of Delta7 and Delta11 16:1 fatty acids. Phylogenetic analysis of the brine-seawater interface sample revealed the presence of various bacterial 16S rRNA gene sequences dominated by cultivated members of the bacterial domain, with the majority affiliated with the genus Halanaerobium. The new Halanaerobium 16S rRNA clone sequences showed the highest similarity (99.9%) to the sequence of isolate KT-8-13 from the Kebrit Deep brine. In this initial survey, our polyphasic approach demonstrates that novel halophiles thrive in the anaerobic, deep-sea brine pool of the Kebrit Deep, Red Sea. They may contribute significantly to the anaerobic degradation of organic matter enriched at the brine-seawater interface.

Bacteria, Anaerobic↗
PubMed2001

Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin.

Pulmonary fibrosis is a chronic progressive disease with no effective therapy. Transforming growth factor beta (TGF-beta) is thought to be a key profibrotic mediator and blocking its activity is therefore one of the targets of new treatment strategies for fibrosis. Decorin is an endogenous proteoglycan and one of the known inhibitors of TGF-beta. The short half-life of peptide-based therapeutics makes gene transfer a promising approach to achieve prolonged protein levels in the lung. Replication-deficient adenovirus was used to deliver decorin transgene (AdDec) to the airways by a single intranasal injection in a murine bleomycin model of lung fibrosis. The ability of vector-derived decorin to inhibit TGF-beta was examined in a bioassay and its effect on bleomycin-induced pulmonary fibrosis was determined by histomorphology and lung hydroxyproline. In vitro, supernatant from cells infected with AdDec abrogated the bioactivity of TGF-beta in a dose-dependent manner whereas control virus (AdDL70) had no effect. In vivo, treatment of bleomycin-injected mice with AdDec substantially reduced the fibrogenic response compared with control virus (hydroxyproline: bleomycin/AdDec, 1.96 microg/mg; bleomycin/AdDL70, 3.05 microg/mg; p = 0.0005). These results suggest that a single administration of AdDec was able to generate a local pulmonary environment that effectively blocked the fibrogenic response to bleomycin by inhibition of TGF-beta.

Adenoviridae↗