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Biomedical subjects

M Friedrich

Publications and source records attributed to M Friedrich.

At least 19 recordsLinked to original sources
PubMed1998

MRI of the breast: state of the art.

Contrast-enhanced MRI of the breast is probably the most sensitive method to detect breast pathology. It is best used to improve the sensitivity of mammography and sonography in selected patient groups with high breast cancer prevalence, where conventional methods are known to be less sensitive. Despite the high sensitivity of MRI, 5-12 % of invasive carcinomas are not recognized during MRI, because of lack of the typical criteria of carcinoma. MRI is probably inferior to mammography in detecting ductal in-situ carcinoma or very small carcinomas (< 3 mm), because the neo-angiogenesis induced by these small carcinomas is too faint to be detected by contrast-enhanced MRI. These tumours cannot be excluded by a normal MRI examination. MRI is non-specific as the distinction of benign and malignant breast lesions is unreliable. Only in selected cases (fat- or blood-containing lesions) may it improve the specificity of mammography and sonography. Mostly image-guided core biopsy is by far the most specific and least expensive method to establish a definitive diagnosis. For lesions exclusively detected by contrast-enhanced MRI, simple and reliable localisation devices are urgently needed. Presently accepted indications for MRI of the breast are: patients with silicone implants after mastectomy or augmentation mammoplasty (detection of recurrence/prosthesis rupture/silicon leakage); patients whose breasts are difficult to evaluate by combined mammography and sonography, who have had breast conservation therapy (local recurrence), or who have proven carcinoma in one breast (multifocality/-centricity or contralateral breast carcinoma) or proven axillary lymph node metastases from an unknown primary tumor, especially when these are hormone receptor positive; patients with extensive postoperative scarring. In the future, genetically defined high breast cancer risk may become an indication.

Adult↗
PubMed1998

Combined exercise and motivation program: effect on the compliance and level of disability of patients with chronic low back pain: a randomized controlled trial.

OBJECTIVE: To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain. DESIGN: A double-blind prospective randomized controlled trial. SETTING: Physical therapy outpatient department, tertiary care. PATIENTS: Ninety-three low back pain patients were randomly assigned to either a standard exercise program (n = 49) or a combined exercise and motivation program (n = 44). INTERVENTIONS: Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination. The motivation program consisted of five compliance-enhancing interventions. Follow-up assessments were performed at 3 1/2 weeks, 4 months, and 12 months. MAIN OUTCOME MEASURES: Disability (low back outcome score), pain intensity, physical impairment (modified Waddell score, fingertip-to-floor distance, abdominal muscle strength), working ability, motivation, and compliance. RESULTS: The patients in the motivation group were significantly more likely to attend their exercise therapy appointments (p = .0005). Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score (p = .004) and pain intensity (p < or = .026). At 4 months, there was a significant advantage for the motivation group in the fingertip-to-floor distance (p = .01) and in abdominal muscle strength (p = .018). No significant differences were found in motivation scores, self-reported compliance with long-term exercise, and modified Waddell score. In terms of working ability, there was a trend favoring the combined exercise and motivation program. CONCLUSION: The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions, ie, short-term compliance, and reduced disability and pain levels by the 12-month follow-up. However, there was no difference between the motivation and control groups with regard to long-term exercise compliance.

Abdominal Muscles↗
PubMed1998

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.

Adenocarcinoma↗
PubMed1998

Intra- and infrahepatic agenesis of the inferior vena cava with azygos continuation accompanied by duplication of the postrenal segment.

Agenesis of one or more segments and duplication of the infrarenal segment are, individually, rare abdominal variants of the inferior vena cava (IVC). In this article, the authors report on a case in which these two anomalies occurred concurrently. Details of the embryology are presented insofar as they are necessary for an understanding of this IVC variant. Spiral computed tomography makes it possible to define the vascular morphology and to make a differentiation from lymphadenopathy. Cavography gives an overall picture of the vascular morphology.

Abnormalities, Multiple↗
PubMed1997

Influence of monomethylfumarate on monocytic cytokine formation--explanation for adverse and therapeutic effects in psoriasis?

Although the effectiveness of systemic antipsoriatic treatment with fumaric acid esters has been proven, their mode of action is still not understood. Recent results indicate their potency in inducing cytokine production in stimulated T cells. Since monocytes and their cytokines are also considered to be of pathogenic importance in psoriasis, we investigated the effect of monomethylfumarate (MMF) on proinflammatory (TNF-alpha, IL-12) and antiinflammatory (IL-10, IL-1RA) cytokine production by peripheral blood mononuclear cells (PBMC) and separated monocytes. In 24-h PBMC cultures from both psoriatic patients (n = 6-13) and healthy volunteers (n = 7-9), MMF at 100 microM induced secretion of TNF-alpha, IL-10, and IL-1RA. Kinetics of IL-10 protein and mRNA expression indicated de novo production. Moreover, MMF significantly augmented endotoxin-induced synthesis of TNF-alpha, IL-10 and IL-1RA. In contrast, no influence on IL-12 secretion was found. Similar effects of MMF in purified monocytes indicated these cells to be responsible for aberrant cytokine formation. Furthermore, enhanced expression of costimulatory molecules after MMF stimulation confirmed monocyte activation. Multiple restimulation with fumaric acid esters in vitro, however, and immunomonitoring in a patient during Fumaderm initial therapy suggested that initial monocyte activation is followed by subsequent deactivation associated with an antiinflammatory response. Our results may explain the well-known effects of therapy with fumaric acid esters. Thus, initial treatment is often accompanied by adverse effects which may be caused by MMF-induced TNF-alpha formation. The change in the IL-10/IL-12 balance as a result of elective induction of IL-10, however, may have antipsoriatic activity by diminishing type-1/proinflammatory cytokine over-expression and the antigen-presenting capacity of monocytes/macrophages, and by upregulation of IL-1RA.

Cells, Cultured↗
PubMed1997

An episodic change of rDNA nucleotide substitution rate has occurred during the emergence of the insect order Diptera.

We have studied the potential reasons for a conspicuous deviation of substitution rates in Dipteran ribosomal genes. Systematic pairwise relative-rate tests reveal that a significant increase in substitution rate is characteristic for Diptera, but not for the other insects analyzed. Estimation of sequence change in specific lineages reveals that most of these substitutions took place during the evolution of the Dipteran stem lineage. When related to the paleontologically documented periods of absolute time, the substitution rate in the stem lineage of the Diptera underwent an at least 20-fold increase compared to other insect groups and subsequently dropped by a factor of 10 before the diversification of the major Dipteran subgroups. Systematic comparisons of nucleotide composition show that this episodic change in substitution rate was accompanied by a significant increase in A+T content of Dipteran rDNA. Our data suggest that the episodic evolution of the Dipteran rDNA has most probably been caused by a change of directional mutation pressure which must have occurred during the evolution of the stem lineage of the Diptera.

Animals↗
PubMed1997

Enhanced expression of T-cell activation and natural killer cell antigens indicates systemic anti-tumor response in early primary cutaneous T-cell lymphoma.

Indolent, primary cutaneous T-cell lymphomas (CTCL) are characterized by hyper-proliferation of malignant T-helper cells in the skin with a favorable prognosis in the early stages. Cytotoxic T cells (CTLs) are believed to be of major importance for tumor surveillance, but there is not yet sufficient evidence for a systemic anti-tumor response in mycosis fungoides (MF). On the contrary, there are hints of systemic immunodepression. We wondered whether signs of a systemic anti-tumor response were demonstrable in peripheral blood of patients with MF and CD30+ pleomorphic T cell lymphoma. Using multiparameter flow cytometry, we investigated blood samples from 39 CTCL patients at different stages and compared them with those from patients with psoriasis, atopic dermatitis, and healthy volunteers. In CTCL patients, an elevated number of lymphocytes expressing natural killer cell markers were found, as well as considerable T-cell activation, indicated by increased percentages of T cells expressing HLA-DR, IL-2 receptor alpha-chain, and transferrin receptor. The CD8+ T cells, which were the most strongly activated T-cell subset, were of polyclonal origin, as shown by their usage of different T-cell receptor families. The enhanced expression of activation antigens was associated with an increased proportion of CD8+ T cells with high expression of the adhesion molecule LFA-1, demonstrating the capacity for migration of these cells. These CD8+ effector cells are suspected to be CTLs and may be responsible for the favorable prognosis of indolent, primary CTCL. Interestingly, a stage-dependent decrease in T-cell activation antigen expression was observed, suggesting the development of a lack in tumor surveillance in advanced MF stages. Further investigations are necessary to verify whether any of the parameters determined are of predictive value for prognosis and response to therapy in CTCL.

Adult↗
PubMed1997

ANP protects against reoxygenation-induced hypercontracture in adult cardiomyocytes.

It was investigated whether atrial natriuretic peptide (ANP) or the related peptide urodilatin can be used for protecting cardiomyocytes against reoxygenation-induced hypercontracture. Isolated ventricular cardiomyocytes (from adult rats) were used as the experimental model. When the cells were submitted to substrate-free anoxia (135 min) and subsequent reoxygenation (30 min), the onset of reoxygenation provoked their hypercontracture. It was studied whether the temporary presence of ANP or urodilatin (1 nM to 1 microM) or 8-bromo-guanosine 3',5'-cyclic monophosphate (8-BrcGMP; 1 microM to 1 mM) during the last 15 min of anoxia and the first 15 min of reoxygenation prevented hypercontracture. It was found that ANP (1 microM) prevented hypercontracture in 82 +/- 8% (SD), urodilatin (1 microM) in 80 +/- 9%, and 8-BrcGMP (1 mM) in 72 +/- 10% of the cells (n = 40 cells). When ANP (1 microM) was added during the last 15 min of anoxia and the first 15 min of reoxygenation, the cellular concentration of cGMP increased from 0.41 +/- 0.04 to 2.80 +/- 0.81 pmol/mg protein (n = 6 cultures). The results show that the reoxygenation-induced hypercontracture in cardiomyocytes can be attenuated by the temporary presence of the stimulators of particulate guanylate cyclase, ANP or urodilatin.

Aerobiosis↗
PubMed1996

Functional interaction between K(ATP) channels and the Na(+)-K(+) pump in metabolically inhibited heart cells of the guinea-pig.

1. Transmembrane current through ATP-regulated K(+) channels (IK(ATP)) was measured in ventricular heart cells of the guinea-pig in the whole-cell and cell-attached patch configurations under conditions of metabolic poisoning with the mitochondrial uncoupler 2,4-dinitrophenol (DNP). 2. Maintained exposure of the cells to DNP resulted in a transient appearance of whole-cell IK(ATP) When IK(ATP) had reached several nanoamps, blocking the forward-running Na(+)-K(+) pump with 0.5 mM strophanthidin decreased IK(ATP) after a delay. The time course of this decrease could be described by a single exponential function, which yielded a time constant(T)of 4.51+/- 1.89 s (n=8). 3. Hyperpolarization from 0 mV to -100 or -150 mV for 2 s caused IK(ATP) (measured at 0 mV) to decrease by 34.2 +/- 14.1 % (n = 8) and 37.6 +/- 9.4% (n = 8), respectively. After the hyperpolarizing pulse, IK(ATP) returned to its higher initial level within a couple of seconds. 4. Driving the pump backwards by removing the extracellular K(+) ions caused the permanent disappearance of DNP-induced IK(ATP). 5. Application of 0.5 mM strophanthidin in the absence of external K(+) ions induced a transient increase in IK(ATP), as did washing out the glycoside (n = 5). 6. When pump action was inhibited by using Na(+), K(+)-free Tyrode solution (see Methods) in the bath, strophanthidin did not have a comparable direct effect on IK(ATP). 7. In cell-attached patches, strophanthidin applied via the bath caused a reduction in IK(ATP) with a similar time course to that in whole-cell experiments. This suggests that the interaction between the pump molecules and the K(ATP) channels is not restricted to closely neighbouring molecules. 8. The data support the hypothesis that [ATP] at the cytosolic face of the membrane may drop to practically zero, thereby passing an 'ATP window' in which the channels first open and then close, and that the submembrane [ATP] is readily controlled by the cytosolic [ATP].

2,4-Dinitrophenol↗
PubMed1996

Sulfogriseofulvin derivatives. synthesis by [4 + 2]cycloaddition, structure, properties, crystal structure analysis, and antifungal activity of spiro[1,3-benzoxathiole-2,1'-cyclohex-2'-en]-4'-one 3,3-dioxides.

Syntheses of substituted, especially of fluoro substituted benzoxathiole 1,1-dioxides, are described. These derivatives were transformed via the Peterson olefination into substituted 2-alkylidene derivatives 27. Diels-Alder reactions of 27 with 1,1-dimethoxy- and 1-methoxy-3-trimethylsiloxy-1,3-butadiene (30, 32) gave sulfone analogues 31 of griseofulvin (named sulfogriseofulvins). From Z-27, a number of cis-isomers with the relative stereochemistry of griseofulvin (cis-31) was prepared, and from E-isomers of 27, compounds (trans-31) with relative stereochemistry of epigriseofulvin were obtained. Some related compounds (33, 38) are synthesized by slight modifications. The stereochemistry is established by spectroscopic methods and crystal structure analyses. The compounds 31 were tested against three species of dermatophytes. The biological activities were all significantly lower than that of griseofulvin.

Antifungal Agents↗
PubMed1996

Isolation of a metal-binding protein from ovaries of dab (Limanda limanda L.) distinct from metallothionein: effect of cadmium exposure.

Metal-binding proteins were isolated from ovaries of dab (Limanda limanda L.) caught in the North Sea. Separation of the heat-treated cytosolic fraction of dab ovaries by gel-filtration chromatography revealed the presence of a major zinc-binding protein with a low-molecular-weight of 10,000-12,000 Da, similar to mammalian metallothionein (MT). The metal-binding protein was analyzed by anion-exchange chromatography and by reversedphase high-performance liquid chromatography. The metal-binding protein from dab ovaries consists of one major isoform. Zinc could be displaced from the isoform by a saturation of the extract with cadmium, leading to altered retention of the protein at the RP column. In a laboratory experiment, dabs were treated intraperitoneally with cadmium (0.5 and 1.5 mg/kg body wt). In contrast to hepatic dab MT, the metal-binding protein in ovaries was not inducable by cadmium; however, dose-dependent amounts of cadmium were bound to the ovarian protein after the metal exposure. The amino acid composition was different from that of mammalian MT. The results suggest that the metal-binding protein in dab ovaries is possibly involved in ovary development and can be affected by cadmium exposure.

Animals↗
PubMed1996

Contribution to the mechanism of chromate nephrotoxicity in developing rats: EPR investigations.

The effect of 2 mg and 1 mg Na2Cr2O7 (Cr)/100 g body wt. on renal function was investigated in 10- and 55-day-old rats, respectively. These doses were followed by equal Cr concentrations in the renal tissue of both age groups. Confirming previous data we found lower nephrotoxicity in young than in adult rats. The concentration of glutathione (GSH) and the activity of glutathione reductase (GSSG reductase) in renal tissue of adult rats were diminished by buthionine sulfoximine (BSO) and lomustine (CCNU) administration, respectively. In these animals Cr nephrotoxicity was decreased significantly. Lower nephrotoxicity was accompanied by slower disappearance of Cr(VI) from renal tissue homogenate in vitro. The time course of Cr(VI) reduction demonstrated by the signal intensity of Cr(V), as recorded by electron spin resonance (EPR) spectroscopy in the supernatant of renal tissue homogenate, enabled us to follow the reduction of Cr(VI) to Cr(III) via Cr(V). Maximally reached Cr(V) concentrations lowest in young rats, did not differ significantly in adult control and BSO and BSO + CCNU treated rats. Further reduction of Cr(V) to Cr(III) which appeared most rapidly in adult rats, was delayed by pretreatment with BSO and CCNU. From our results we concluded that (1) reduction of Cr(VI) was more related to the concentration of GSH than to the activity of GSSG reductase, (2) the formation of Cr-GSH-complexes with GSH oxidation seemed to be the first step of Cr(VI) metabolism, and (3) the stabilization of reactive Cr(V) by GSH seemed to be decisive for the preventive effect of BSO and CCNU as well as for age differences in chromate nephrotoxicity.

Age Factors↗
PubMed1996

IL-7 mRNA is not overexpressed in mycosis fungoides and pleomorphic T-cell lymphoma and is likely to be an autocrine growth factor in vivo.

Interleukin-7 (IL-7) is thought to be a growth factor for cutaneous T-cell lymphoma (CTCL) since it has been shown that IL-7 transgenic mice develop a cutaneous disorder characterized by enhanced T-cell proliferation with progression to malignancy and that in vitro growth of Sézary cell lines is IL-7 dependent. However, no direct in vivo evidence exists for the involvement of IL-7 in the pathogenesis of CTCL. Therefore, we examined IL-7 mRNA expression in skin biopsies from patients with mycosis fungoides (MF) (n = 20) and pleomorphic T-cell lymphoma (n = 5). By semiquantitative RT-PCR, IL-7 mRNA was not detectable in any of the CTCL samples, or in normal human skin (n = 8) or in skin from patients with psoriasis (n = 7) or atopic dermatitis (n = 5). In contrast, IL-7 mRNA was detected in a biopsy from a kidney allograft transplant, in normal keratinocytes under various culture conditions and in several cell lines. Interestingly, using a highly sensitive nested PCR, IL-7 mRNA was detectable in all specimens tested, but there was no indication of IL-7 overexpression in MF then analysing lesions of patch, plaque or tumour stages. In contrast, increasing CD3 expression was found, which was most likely a consequence of the enhanced density of malignant T cells in advanced tumour stages. In summary, by the use of semiquantitative RT-PCR we were not able to detect IL-7 overexpression in MF or pleomorphic T-cell lymphoma. This indicates that IL-7 is probably not an autocrine growth factor in these CTCLs.

Adult↗
PubMed1996

Influence of exogenous and endogenous acth on adrenal cortex activity in calves during the early postnatal period.

A study was carried out on 66 black-and-white calves during the period from birth (day 0) to day 21 of life. Blood plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined by radio-immunoassay and the influence of exogenous and endogenous ACTH on adrenocortical activity assessed. An ACTH-induced adrenal cortex response was observed as early as day 0, whereas a definite relationship between ACTH and cortisol concentrations emerged in the second week of life. It is concluded that the pituitary-adrenal axis is blocked during the first week of life and this effect seems to be related to high cortisol concentrations and an elevated reactivity threshold of the adrenal ACTH receptors.

Adrenal Cortex↗