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Biomedical subjects

M Franke

Publications and source records attributed to M Franke.

At least 19 recordsLinked to original sources

[Thermoradiotherapy with interstitial thermoseeds in treatment of local prostatic carcinoma. Initial results of a phase II study].

Several experimental data are available regarding the efficacy of the combination of interstitial hyperthermia and conformal radiation therapy. We planned a phase II trial as a member of the special hyperthermia research group of the Deutsche Forschungsgemeinschaft (German Research Society) to determine the efficacy of thermoradiotherapy using interstitial cobalt-palladium thermoseeds in the treatment of patients with localized prostate cancer. Forty-one patients with localized prostate cancer were enrolled in the study between July 1997 and April 2000. The interstitial hyperthermia induced in a magnetic field was applied in six sessions once a week. Conformal three-dimensional radiation therapy was given simultaneously in daily fractions of 1.8 Gy with a total dose of 68.4 Gy. We measured intraprostatic temperatures between 42 degrees and 46 degrees C. No major side effects were observed during the hyperthermia session. The median level of prostate-specific antigen (PSA) decreased from 11.25 ng/ml to 0.88 ng/ml 3 months after treatment and to 0.38 ng/ml 12 months after treatment with a median follow-up of 10 months. The mean prostate volume decreased from 32.6 ml to 26 ml after 3 months of treatment and to 18.5 ml after 12 months. Interstitial hyperthermia is a feasible, well-tolerated procedure in prostate cancer therapy. A significant PSA decrease was observed. Longer follow-up is necessary to determine the efficacy.

Aged↗

Prostate-specific antigen in female urine: a prospective study involving 217 women.

OBJECTIVES: Histomorphologic studies have provided evidence of prostate-specific antigen (PSA)-producing tissue in the female urethra. Some urine samples from women in a small series were positive for PSA, but no systematic investigation of this subject has been done to date. METHODS: In a prospective study, we analyzed whether PSA occurs in the urine of women and what factors induce detectable PSA levels. The urine samples of 217 women were analyzed (Hybritech-Tandem E-PSA) under standardized conditions. The impact of urine pH and volume was investigated, and the results were correlated with clinical data (age, residual urine, urinary tract infection and prior sexual intercourse within 48 hours). RESULTS: A positive PSA level greater than the detection limit of 0.1 ng/mL was found in 11% of the analyzed samples; their mean value was 0.29 ng/mL. pH correction did not result in a significant difference. The voiding volume had no influence on the PSA level. Among the cases of detectable PSA, women younger than 50 years of age (n = 14) had a mean PSA of 0.34 ng/mL and those older than 50 years (n = 9) a mean of 0.23 ng/mL. One of 9 women with and 22 of 208 women without residual urine volume had a detectable PSA level, as did 0 of 20 with and 23 of 197 women without urinary tract infection, and 3 of 7 with and 20 of 210 women without prior sexual intercourse within the previous 48 hours. None of the differences were significant. CONCLUSIONS: A urine PSA level was detected in 11% of all women studied, with PSA values apparently age dependent. Any urine portion is suitable for analysis. No influence was determined for residual urine volume or urinary tract infection. Sexual intercourse may cause detectable PSA values, but the data of this study did not provide sufficient evidence for this hypothesis.

Adult↗

Expression of individual copies of Methylococcus capsulatus bath particulate methane monooxygenase genes.

The expression of the two gene clusters encoding the particulate methane monooxygenase (pMMO) in Methylococcus capsulatus Bath was assessed by analysis of transcripts and by use of chromosomal gene fusions. The results suggest that the two clusters are functionally redundant but that relative expression alters depending on the copper levels available for growth.

Artificial Gene Fusion↗

Stereolithographic biomodeling to create tangible hard copies of cardiac structures from echocardiographic data: in vitro and in vivo validation.

OBJECTIVES: This study investigated the feasibility, accuracy and clinical potential of creating polymer hard copies of echocardiographic data using stereolithography. BACKGROUND: Three-dimensional (3D) echocardiography has so far been limited by the need to display reconstructed 3D objects on a two-dimensional screen. Thus, tangible stereolithographic polymer models created from echocardiographic data could enhance our spatial perception of cardiac anatomy and pathology. METHODS: Hard-copy replicas of water-filled latex balloon phantoms (n = 7) and porcine liver specimens (n = 12) were generated from echocardiographic images using stereolithography (computerized laser polymerization). In addition, we created 24 models of the mitral valve from 12 transesophageal studies (normal = 6, mitral stenosis n = 4, prolapse/flail leaflet n = 8, annular dilation n = 2, leaflet restriction n = 2 and following mitral valve repair n = 2). RESULTS: Excellent agreement was found for comparison of volumes (r = 0.98, SEE = 3.46 mm3, mean difference = 0.25 +/- 3.33 mm3) and maximal dimensions (r = 0.99, SEE = 0.16 cm, mean difference = 0.03 +/- 0.16 cm) between phantoms and their corresponding replicas. Visual and tactile examination of mitral valve models by two blinded observers allowed correct depiction of mitral valve anatomy and pathology in all cases. CONCLUSIONS: Stereolithographic modeling of echocardiographic images is feasible and provides tangible polyacrylic models that are true to scale, shape and volume. Such models offer accurate depiction of mitral valve anatomy and pathology in patients studied with transesophageal echocardiography. This technique could have substantial impact on diagnosis, management and preoperative planning in complex cardiovascular disorders.

Computer Systems↗

[Postoperative peripheral neuropathies in general surgery].

INTRODUCTION: Postoperative nerve lesions beyond the operative area, the so called positioning traumas are considered uncommon in general surgery. But they can have serious consequences for the patient and the surgeon, including forensic sequelae. The objective of this work was to describe the incidence, pattern, risk factors and course of postoperative neuropathies in general surgery and to identify indicators to prevent these complications. METHODS: Based on neurologic records we reviewed all postoperative peripheral neuropathies that occurred in the Department of General Surgery of the University Hospital Freiburg in the time period from January 1979 to December 1990. Lesions that occurred as a direct operative effect were excluded. RESULTS: In 35 patients 50 nerve lesions were observed, representing an incidence of 0.12% of all operations during this time period. Most frequently lesions of the n. peroneus occurred, followed by the n. ulnaris, n. cutaneous femoris lateralis and n. medianus. Nerve lesions were observed in every body position and as early as after 15 min. Postoperative nerve lesions have a favorable prognosis. DISCUSSION: Nerve lesions caused by positioning can occur during any operation with any duration in general surgery. They should be avoided by thorough and careful positioning. Also the patient must be informed about the possibility of nerve lesions caused by the positioning.

Adult↗

Expression and activity of mitogen activated protein kinases in human colorectal carcinoma.

BACKGROUND: Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown. AIMS: To establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa. METHODS: The expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays. RESULTS: After immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found. CONCLUSIONS: Inactivation of p42 MAPK could be associated with colonic carcinogenesis.

Adenoma↗

Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes.

Opsonophagocytic killing of some bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) by phagocytes is enhanced by previous brief exposure of the organism to antibiotics. We studied the regrowth of Legionella pneumophila previously pretreated with levofloxacin, erythromycin and/or rifampicin in human monocytes. The MIC for the L. pneumophila isolate of levofloxacin, erythromycin and rifampicin was 0.03, 0.5 and 0.001 mg/L, respectively. Growth of L. pneumophila from buffered charcoal yeast extract (BCYE) agar for 24 h was subcultured into BYE broth containing from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin. After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms were washed and opsonized with 20% heat inactivated pooled normal human serum. Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio) previously adhered to wells in tissue culture plates containing RPMI and 10% fetal calf serum. After 0, 24, 48 and 72 h of incubation, quantitative cultures of lysed human monocytes were done on BCYE agar. Our results indicate effective inhibition on L. pneumophila at 0 h regardless of the antibiotic (levofloxacin, rifampicin or erythromycin) or their concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, recovery and regrowth of L. pneumophila were both antibiotic- and concentration-dependent. In comparison with controls (no antibiotic pretreatment), peak regrowth of L. pneumophila pretreated with either 1x MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and reduced (30% of control peak regrowth). Regrowth of L. pneumophila pretreated with 1x MIC of rifampicin continued beyond 72 h. Pretreatment with levofloxacin at 4x MIC caused the greatest degree of growth inhibition (2 log10). In contrast, at 72 h, regrowth of organisms pretreated with 4x MIC of erythromycin or rifampicin was less than peak control (P < 0.01) but greater than that seen with levofloxacin (P < 0.01). The rate and degree of regrowth of L. pneumophila pretreated with combinations of levofloxacin or erythromycin with rifampicin, or levofloxacin with erythromycin (all at 1x MIC) was similar to that seen with single drugs. Thus, significant delay and reduction of regrowth in this phagocytic system occurred with levofloxacin only. Prolonged exposure of the organism at 4x MIC levofloxacin concentrations was effective in suppressing regrowth of pretreated L. pneumophila in human monocytes.

Anti-Bacterial Agents↗

Extraction of selected drugs from serum using microwave irradiation.

Microwave irradiation is used as an alternative heating method for extraction over more conventional hot plate methods. We describe a fast, efficient method for the determination of selected drugs in human blood/serum using microwave extraction. The microwave extraction of organic substances requires special instrumentation and the results have been compared with the results from classical liquid/liquid extraction. The present microwave extractions were performed in an 'atmospheric pressure' system. Before irradiation with microwaves, an appropriate solvent mixture was added to the buffered specimen. Lidocaine, methadone, diazepam, nordiazepam, propoxyphene and norpropoxyphene were tested as model substances. The quantitation was performed by GC/NPD. The procedure has been applied successfully to a number of forensic cases. The use of microwaves decreases the time of extraction and the solvent consumption.

Analgesics↗

Serum antibody concentrations of cytotoxin, exotoxin, A, lipopolysaccharide, protease, and elastase and survival of patients with Pseudomonas aeruginosa bacteremia.

The relationship between survival and serum concentrations of antibody to cytotoxin, exotoxin A, lipopolysaccharide (LPS; IgM and IgG), protease, and elastase (determined by enzyme-linked immunosorbent assay) was studied in a group of 41 patients with Pseudomonas aeruginosa bacteremia. The lowest mean concentrations of antibody to cytotoxin (P < .05) and of IgG to LPS (P < .01) were noted in the patients who died within 48 hours of onset. The mean level of antibody to cytotoxin in patients who died 9-45 days or 5-22 months following onset was similar to that in controls, while in patients who survived > or = 24 months the level was higher than in controls (P < .01). The mean level of IgG to LPS was highest in patients who survived > or = 24 months. The mean concentrations of antibody to the other antigens (except IgM to LPS) were higher in patients than in controls (P < .01). No significant change occurred in any mean antibody concentrations over time. Administration of antipseudomonal antibodies, especially to cytotoxin and LPS, should be considered in the early stages of therapy for patients with P. aeruginosa bacteremia.

ADP Ribose Transferases↗

The genomic structure of the human UBE1L gene.

The human UBE1L gene, for which the product may well play a role in the ubiquitin system because of its high degree of identity to the ubiquitin activating enzyme, is located at 3p21, a chromosomal region consistently showing loss of heterozygosity in lung cancer. The finding that UBE1L is well expressed in normal lung tissue, but hardly or not in lung cancer-derived cell lines, prompted us to investigate its genomic structure to find an explanation for the lack of expression in lung cancer. The gene has 22 exons distributed over 8.4 kb. Both anchored PCR experiments and mapping of DNase I-hypersensitive sites point to the region immediately upstream of exon 1 as the promoter site. Three moderately to well-informative polymorphisms were found, of which one is easily directly detectable. Cancer-specific mutations were not detected. The lack of expression in lung cancer cell lines correlated with a highly decreased sensitivity towards DNAse I of the promoter region and with an almost complete methylation of the HhaI site in the first exon. 5'-Azacytidine-induced demethylation did not result in a marked increase of the UBE1L mRNA level in the tumor cell lines. This leaves the possibility that mutation or absence of yet unknown transcription factors causes a regulatory block of the UBE1L gene.

Base Sequence↗

A homozygous deletion in a small cell lung cancer cell line involving a 3p21 region with a marked instability in yeast artificial chromosomes.

All types of lung carcinoma are characterized by a high frequency of loss of sequences from the short arm of chromosome 3, the smallest region of overlap containing D3F15S2 in band p21. Here we characterize a 440-kilobase segment from this region, which we found homozygously deleted in one of our small cell lung cancer-derived cell lines. The homozygous deletion maps between UBE1L and ZnF16, just centromeric to D3F15S2. Yeast artificial chromosomes with inserts originating from the deleted region are very unstable and readily lose parts of their insert.

Base Sequence↗

Pseudomonas aeruginosa cytotoxin as a pathogenicity factor in a systemic infection of leukopenic mice.

The effect of Pseudomonas aeruginosa cytotoxin was assessed in leukopenic outbred Swiss male mice (20 g) using a high cytotoxin-producing strain (PA158) and its cytotoxin-deficient isogenic mutant (PA114F5) generated by Tn7::Tn5 transposon mutagenesis of PA158. Leukopenia was induced by intraperitoneal (i.p.) administration of cyclophosphamide (150 micrograms/g). Anesthetized mice were infected via a 4 mm incision on the shaved back with 300 CFU/mouse (9 LD50; expected death rate 85%). Precleared mouse cytotoxin-specific heat inactivated rabbit polyclonal antibody (RPA) was administered i.p. (0.2 ml) 24 hr before challenge. Controls received i.p. normal rabbit serum, RPA, cyclophosphamide alone, or a sham procedure. Challenge with the high cytotoxin-producing strain PA158 caused earlier and a significantly greater mortality than that observed with a cytotoxin-deficient strain PA114F5 (P < 0.01). Cytotoxin-specific polyclonal antibody was protective. Pretreatment with antibody decreased the mortality rate following challenge with PA158 from 88.9% to 27.8% (P < 0.01). Pretreatment with antibody decreased the mortality rate following challenge with PA114F5 from 27.8% to 5.6% (P < 0.05). These results demonstrate that P. aeruginosa cytotoxin contributes to the pathogenicity of the organism and that cytotoxin antibody is protective in a systemic P. aeruginosa infection in leukopenic mice.

Analysis of Variance↗

Constant intravenous pentoxifylline infusions in allogeneic marrow transplant recipients: results of a dose escalation study.

An uncontrolled open prospective dose escalation study of daily constant-rate 24-h i.v. pentoxifylline (PTX) infusions was performed in 24 consecutive adult patients with hematologic malignancies undergoing allogeneic BMT. The objective of this study was to determine the maximum tolerable dose and to evaluate steady-state plasma concentrations of PTX and its major active 5-hydroxylated metabolite (MI) with this application route. On each of three dose levels of PTX (10, 15 and 20 mg/kg/day), eight patients were enrolled in this study. The prominent dose-dependent and dose-limiting adverse effect attributable to PTX infusions was moderate to severe nausea and vomiting which occurred on the 15 mg/kg and 20 mg/kg dose levels. In addition, one patient on each of the higher doses developed central nervous system toxicity which manifested as acute obtundation and myoclonias. Monitoring of steady-state plasma concentrations revealed that metabolite MI contributed 70-80% to both active compounds with a dose-dependent increase of parent drug and metabolite MI concentrations. In patients pretreated by high-dose busulfan and cyclophosphamide (CY), steady-state plasma concentrations of metabolite MI were significantly increased on all dose levels over those of patients who received total body irradiation and CY as a preparative regimen. Furthermore, impairment of excretory liver function led to significant accumulation of parent drug and metabolite MI. In conclusion, constant i.v. PTX infusions in allogeneic marrow transplant recipients are limited by dose-dependent nausea and vomiting with an estimated maximum tolerable dose in the range of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗