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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 595 records · Page 33Linked to original sources

[Combination of bilateral pelvic lymphadenectomy, permanent iodine-125 implantation and percutaneous irradiation of localized prostate carcinoma. 1: Methods and results].

Since the beginning of 1981, 32 patients at an age of 52 to 72 years who suffered from a locally confined adenocarcinoma of the prostate were treated by permanent implantation of iodine-125 seeds at the Urologic and Radiotherapeutic Hospital of the University of Erlangen. 25 patients were evaluated after a median observation period of 30 months. The first group consisting of 19 patients was submitted to a combined percutaneous and interstitial treatment, the other six patients were initially treated only by interstitial therapy because of severe complications observed in the meantime. After bilateral pelvic staging lymphadenectomy, permanent iodine-125 seeds were implanted into the patients of stage T1, T2, early T3, and pN0-1, in case of microscopic lymph node manifestation without capsular perforation also into patients of stage pN2 and pN4. Eight weeks later the patients received a moving beam irradiation with 10 MV photons at the linear accelerator. The centre of the prostate was faded out by a specially constructed H absorber in such a way that the prescribed target dose of 36 Gy in four weeks to the 90%-isodose was only applied to a spherical surface around the implant. One patient died perioperatively from an embolism due to phlebothrombosis of the thigh. 22 out of the other 24 patients are in complete remission, one patient had a local recurrence in the right seminal vesicle which appeared 28 months after primary therapy, and one patient developed skeletal metastases. The objective side effects and late complications of our combined treatment are considerable with respect to their incidence as well as their severity: a slight or medium radioproctitis was found after a latent period of one to two years in 28% (5/18) of cases, after a latent time of about 1 1/2 to two years another 28% (5/18) developed subsequently to a proctitis an urethral stricture and an ulcer situated on the anterior rectum wall facing the prostate, and four patients presented finally a prostato-rectal fistula.

Aged↗

[Combination of bilateral pelvic lymphadenectomy, permanent iodine-125 implantation and percutaneous irradiation of localized prostate carcinoma. 2: Discussion and conclusions].

Severe complications (urethral stricture, ulcer at the anterior rectum wall, prostato-rectal fistula) have been observed in 28%(5/18) of patients treated by combined percutaneous and interstitial therapy for locally confined prostatic cancer. These complications were caused above all by charging the big prostatic volumes with an excessive number of iodine-125 seeds applied through cannulas arranged too closely and by an insufficient distance between the mucous membrane of the rectum and the first seed. The evaluation of our data showed insignificant complications up to a total activity of 28 mCi, slight or medium complications between 28 and 35 mCi, and severe complications between 35 and 40 mCi. It is therefore necessary in case of an intended combination of interstitial and percutaneous irradiation to take precautionary measures already during the implantation in order to avoid critical accumulated doses: the spatial distribution of the seeds may be not so close and the total activity has to be lower (25 to 30 mCi). The MPD (minimal peripheral dose) can be by 30 to 40% below that of implantation alone and the dose in the centre of the implant should not exceed the MPD value by more than 100%. If a considerable volume (greater than 10 cm3) is irradiated by the implant with more than 240 Gy, the percutaneous boost generally performed up to 40 Gy has to be reduced, or the centre of the implant must be shielded by lead satellites after 20 Gy at the latest. The distance between the seeds and the mucous membrane of the rectum should be at least 1 cm, the interval between interstitial and percutaneous irradiation at least 8, better 12 weeks. A percutaneous boost is only performed in case of a very inhomogeneous interstitial dose distribution and a too low MPD (in form of a rotating irradiation up to 30 Gy: 16 Gy by open radiation and 14 Gy with H absorber) or in case of microscopic manifestations in the pelvic lymph nodes or suspected beginning manifestations in the seminal vesicles (in form of a four field irradiation up to 50 Gy using individual secondary collimators in order to shield sound tissues as well as the prostate which is already sufficiently irradiated by the seeds.

Aged↗

Different types of modification in c-fos and its associated protein p39: modulation of DNA binding by phosphorylation.

We have studied the biosynthesis and biochemical properties of the c-fos gene product and its associated protein (p39) in growth factor-stimulated fibroblasts. c-fos is a markedly acidic protein that is extensively post-translationally modified by phosphorylation and another type of modification not changing its relative molecular mass (Mr). More than 10 different forms of c-fos protein can be identified by two-dimensional gel analysis. In c-fos-transformed cells, however, most of the highly modified forms are missing. The affinity for DNA of less phosphorylated c-fos-protein complexes is higher than that of the highly modified ones. The transforming potential of c-fos protein and its affinity for DNA thus seems to be inversely correlated with the extent of its phosphorylation. In contrast to c-fos, p39 is a basic protein that is rendered even more basic by post-translational modification. Two other forms of p39 differing in specific domains of the protein (p41 and p43) were also found to be complexed with c-fos.

Animals↗

On the assessment of the efficacy of pentoxifylline (Trental).

The efficacy of Trental (pentoxifylline) in the treatment of intermittent claudication was evaluated in 14 double-blind randomized studies, involving 475 patients with chronic occlusive vascular disease. In twelve studies which were performed in the USA, different countries of Europe and Australia, a placebo was used as control. Low doses of adenosine or nylidrine respectively, were given to the control groups in the other two studies. A total of 238 patients were allotted to Trental and 237 to the control groups. In most studies, the recommended dosage of Trental was 3 X 400 mg pentoxifylline in sustained release tablets. Twelve of the 14 trials had a duration between 8 and 24 weeks. The efficacy of Trental was established in a reproducible manner through the trial series under different trial designs following the requirements and guidelines from local authorities and medical societies. The number of patients with an improvement in walking distance of more than 100% was four times higher in the Trental group compared with the control group. The superiority of the Trental treatment over the control's persisted also when taking into account risk factors such as diabetes, hypertension, smoking habits and duration of the disease.

Animals↗

Isolation and structural analysis of a biologically active chicken c-fos cDNA: identification of evolutionarily conserved domains in fos protein.

To identify functionally important domains in the fos gene product we have studied the evolutionary divergence between chicken and mammalian fos proteins. A cDNA containing the entire chicken c-fos coding region was isolated and its nucleotide sequence determined. The deduced 367-amino acid sequence was compared to that of the mouse and human proteins. This comparison revealed a highly conserved domain (98% homology between mouse and chicken) in the center of the protein (85 amino acids) that coincides with a region known to be indispensible for transforming activity. This highly charged domain presumably contains contact sites for DNA and other proteins as well as a nuclear location signal sequence. Two other regions, that are dispensable for transformation, are also highly conserved and may thus be important for the physiological function of c-fos. These are the N-terminal 88 amino acids (85% homology) and the C-terminal 62 amino acids (92% homology). The C-terminus not only contains a potential DNA-binding Zn-finger structure but is also the least divergent region in the protein at the nucleotide level (92% conservation between chicken and mouse), supporting the hypothesis that mRNA secondary structures in this region may contribute to post-transcriptional regulatory mechanisms. In contrast, the domains between the terminal sequences and the center region of fos protein show considerable divergence (39% and 45% homology, respectively), indicating a minor role, if any, for these sequences. The significance of these conclusions is emphasized by the observation that the chicken c-fos protein, expressed from the cDNA inserted into a retrovirally-derived expression vector, efficiently induces morphological transformation in rat fibroblasts. The chicken c-fos gene product could be identified by immunoprecipitation and in vitro transcription/translation of the isolated cDNA as a protein of Mr approximately 60 K.

Amino Acid Sequence↗

[Thrombendarterectomy in pelvic artery sections: an wrongly neglected therapeutic procedure?!].

Surgical repair was applied to the aortofemoral region in 491 cases, between 1975 and 1984, including 48.5 per cent of in situ approaches. The ratio were 2.2:1 for aortofemoral thrombendarteriectomy and 4:1 in relation to revascularised extremities. Surgical lethality, postoperative complications, and amputations following aortofemoral thrombendarteriectomy did not differ with significance from conditions in the wake of bypass procedures. Long-time functional results were good to satisfactory in 90.3 per cent of all cases and thus compared well with results obtained from bypass procedures which were of comparable quality in 89.1 per cent. Aortofemoral thrombendarteriectomy, today, is found to be a method which had certainly suffered unwarranted neglect in the past.

Amputation, Surgical↗

[Gaucher disease and pregnancy--a case report].

Reporting an own case the authors describe the unusual combination of Gaucher's Disease and pregnancy. They suggest with regard to the possibility of hepatic and/or lienal rupture in cases with extended hepatosplenomegaly the primary caesarean section.

Adult↗

[Stability of cignolin (dithranol) in ointments containing tar with and without the addition of salicylic acid. Oxidation to danthron and dithranol dimer].

The stability of dithranol in white petrolatum was investigated over a period of 10 weeks in dithranol ointments containing liquor carbonis detergens (LCD) and/or coal tar, in the presence and absence of salicylic acid. Qualitative and semiquantitative analysis using high-pressure liquid chromatography (HPLC) showed that dithranol (0.1%, 0.5%, 1.0%) remained rather stable in white petrolatum for 10 weeks, regardless of the presence or absence of salicylic acid. The addition of 5% LCD or 5% crude coal tar resulted, however, in the rather rapid oxidation of dithranol into its products, danthron and dithranol dimer. The addition of 2% salicylic acid to these combined ointments did not stabilize the dithranol: rather, it reduced the amount of danthron but resulted in a considerable increase in the amount of dithranol dimer. The oxidation of dithranol into its products danthron and dithranol-dimer was almost complete in 0.1% ointments and ranged between 16.3% and 53.8% in 0.5% white petrolatum after 10 weeks. These findings may explain why the addition of tar minimizes dithranol-induced erythema, as reported in clinical studies. Such combinations may have an important influence on the antipsoriatic activity of dithranol and the appearance of brownish discoloration.

Anthralin↗

The protooncogene c-fos is transcriptionally active in normal human granulocytes.

Total cellular RNA of highly purified normal human blood cell populations was analyzed for the expression of the protooncogene c-fos, the cellular counterpart of the transforming FBJ virus. In marked contrast to previous findings based on in vitro studies with permanent leukemic cell lines, c-fos transcription was restricted to granulocytes. Neither blood monocytes nor blood lymphocytes or alveolar macrophages revealed detectable levels of c-fos transcription. Whereas this cellular oncogene is constitutively expressed in granulocytes, the monocytic cell line U-937 showed a transient c-fos transcription only after induction of differentiation. The contradiction between the results found in vivo and in vitro is discussed.

Blood Cells↗