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Biomedical subjects

M Wirth

Publications and source records attributed to M Wirth.

At least 91 records · Page 5Linked to original sources

[Selection criteria for radical prostatectomy with reference to long-term results].

Between July 1969 and May 1991 radical prostatectomies were performed in 410 consecutive patients with prostate cancer at the Department of Urology, University of Würzburg. The calculated survival rates for these 410 patients up to 15 years after surgery are very similar to the life expectancy of the normal male age-matched population. In 127 of the 410 cases radical prostatectomy was carried out more than 10 years ago, so that the data relating to these cases have been definitely observed, not merely statistically evaluated. In order to permit a comparison of our results with those reported in the literature, the TNM classification of 1979 was utilized in this study. This means that only tumors penetrating through the capsule of the prostate were classified as stage pT3. Those tumors that are only infiltrating the apex or the prostatic capsule, are classified as stage pT2. For patients with stage pT1pN0M0 and pT2pN0M0-tumors, 10-year survival rates (90.5% and 70% respectively) were recorded which are even slightly better than those of the normal male age-matched population. For patients with tumors extending through the capsule, the 10-year survival rate was found to be 60%. Forty percent ot these patients with stage pT3pN0M0 disease are alive tumor-free after more than 10 years and can thus be regarded as cured. When lymph node metastases were present (stage pT2-3pN1-2M0), some of the patients appeared to benefit from radical prostatectomy, since 4 out of 11 patients with this stage disease survived for more than 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Chemotherapy in metastasizing prostate carcinoma].

Seventeen patients with metastasized hormone-resistant prostate cancer were treated between January 1986 and October 1989 with combination chemotherapy at the Department of Urology, University of Würzburg Medical School. In 1 of the 17 patients a complete remission lasting 4 months was observed. In 3 patients a partial remission was noted, and in 5 others stable disease for an average of 6.8 months occurred. Tumor progression was seen in 7 patients. In all 16 evaluable cases palliation of tumor pain was achieved with this kind of treatment. The role of chemotherapy in the treatment of metastasized prostate cancer is discussed.

Aged↗

[Chemotherapy of prostatic carcinoma].

The overall results of chemotherapy of hormone-refractory prostate carcinomas are disappointing. In practical terms, only partial remissions are observed. Complete remissions are very rare. Prospective randomized studies revealed no advantage of primary chemotherapy over standard hormone therapy with regard to survival time of patients with metastasized prostate carcinoma. Furthermore, superiority of a combination therapy over therapy with a single cytostatic agent for prostate carcinoma has so far not been proved. These results indicate that chemotherapy of prostate carcinoma should only be applied within controlled studies, and that new substances or combination preparations should preferably be tested in such studies.

Antineoplastic Agents↗

[Ectopic splenic tissue in connection with the testis].

A case of ectopic splenic tissue in the testicle is reported. This congenital anomaly has only ever been seen in the left scrotal compartment. The ectopic splenic tissue is separated from the testicle by a fibrotic capsule. When accessory splenic tissue is suspected on examination of a testicular biopsy a frozen section should be performed; orchiectomy can then often be avoided.

Adult↗

[Pharmacokinetic aspects of dosage increase of recombinant interferon alpha-2B in patients following intraperitoneal and intra-arterial application].

Interferon-alpha-2 b (IFN) was administered as an i.a. bolus at doses of 3 and 5 million international units (MIU), as an i.a. 24h long-time infusion at 3 and 5 MIU and as an i.p. 90 min short-time infusion at 5, 10 and 15 MIU. Dose escalation of IFN on i.p. administration leads to correspondingly elevated AUC values of IFN (correlating to the dose) in the peritoneal fluid (PF) and blood, with a shift of the steady-state at about 2h. Bioavailability of IFN is 30 times higher for PF than for blood. t1/2 el, Vd and total clearance are not influenced by dose escalation in both compartments due to their dose-independency. IFN is eliminated from the PF with t1/2 el = 10-32h and from the blood with t1/2 el = 5-13h. After an i.a. bolus at either dosage IFN is distributed from the blood with a half-life of below 2h. 24h infusion leads to a steady-state within 4-6h and a cmax of 8.5 or 12.5 units/ml, respectively. IFN is slowly eliminated during infusion with a t1/2 el of 16h.

Dose-Response Relationship, Drug↗

Conformational differences between latent and active plasminogen activator inhibitor, PAI-1: a spectroscopic study.

The protein conformation of latent and active PAI-1 has been studied with circular dichroism, absorbance and fluorescence spectroscopy. The far ultraviolet circular dichroism spectrum of latent PAI-1 displays a more negative band at 220 nm than active PAI-1, crossing the baseline at a lower wavelength. Active PAI-1 shows an absorption maximum at lower wavelength (269 nm) than present in latent PAI-1 (278 nm). In consistency, slow denaturation of active PAI-1 by incubation for two hours at 37 degrees C induces a shift in the absorption maximum from 268 nm to 274 nm. The fluorescence emission maximum of latent PAI-1 is at lower wavelength (335 nm) than that of active PAI-1 (340 nm). These spectroscopic differences are interpreted as reflecting a more tight conformation, with the tryptophan residues in a more apolar environment, in latent PAI-1 compared to active PAI-1.

Circular Dichroism↗

A possible contribution of decrease in free fatty acids to low serum triglyceride levels after diets supplemented with n-6 and n-3 polyunsaturated fatty acids.

Intraindividual comparisons of diets supplemented with sunflowerseed oil (rich in linoleic acid, LA, C18:2n-6), linseed oil (enriched with alpha-linolenic acid, LNA, C18:3n-3) and canned mackerel (rich in eicosapentaenoic acid, EPA, C20:5n-3 and docosahexaenoic acid, DHA, C22:6n-3) were made in 30 patients with primary hyperlipoproteinemia (HLP) of phenotypes IIa (n = 9), IIb (n = 7), IV (n = 7) and V (n = 7). The lipid- and blood pressure-lowering effects of polyunsaturated fatty acids (PUFA), particularly those of the EPA- and DHA-rich diet, were confirmed irrespective of the type of HLP. Apolipoproteins A-I and B remained unchanged. The most remarkable finding was a substantial depression of free fatty acids (FFA) within a standardized glucose tolerance test (GTT) associated with the fall of serum triglycerides after diets enriched with n-6 and especially after those supplemented with n-3 PUFA. It was suggested that the decrease of FFA indicates reduced peripheral lipolysis, which might be a hitherto ignored factor involved in the triglyceride-lowering action of n-6 and, more pronounced, of n-3 PUFA.

Adult↗

Extreme decrease of linoleic acid in renal medulla from rats after a diet supplemented with cod liver oil.

Spontaneously hypertensive (SHR) and normotensive rats were fed a diet supplemented with linseed oil or cod liver oil for 22 weeks. The most remarkable finding was an extreme fall of linoleic acid in lipids from renal medulla after cod liver oil supplementation. In free fatty acids (FFA) eicosatrienoic acid (C2): 3n-9) appeared increased as a sign of essential fatty acid (EFA) deficiency.

Animals↗

Blood pressure and serum lipids from SHR after diets supplemented with evening primrose, sunflowerseed or fish oil.

Spontaneously hypertensive rats (SHR) at 4 weeks of age were fed a diet supplemented with sunflowerseed oil (SO), evening primrose oil (EPO), fish oil (FO) or EPO + FO for 22 weeks. A diet with commercially available pellets served as control. Systolic blood pressure was significantly lower during and after FO, EPO and EPO + FO, whereas the lower level after SO was not significant when compared with the controls. Serum triglycerides and total cholesterol were lowest after EPO followed FO. The combination of both EPO and FO resulted in unexpected high values of triglycerides and cholesterol. HDL-cholesterol was likewise highest after EPO + FO. The results indicate a quantitatively different depression of blood pressure and serum lipids from SHR by individual polyunsaturated fatty acids (PUFA).

Animals↗

Diagnostic value of transrectal ultrasound in tumor staging and in the detection of incidental prostatic cancer.

To evaluate the accuracy of transrectal ultrasonography in staging and detection of prostatic cancer, a prospective study was initiated. In 466 patients transrectal ultrasonography was performed before transurethral resection, suprapubic adenomectomy, or radical prostatectomy. The findings were compared with the histopathologic results. In 160 of the 466 patients a carcinoma of the prostate was proven by histology. In 21 patients the cancer was an incidental finding after transurethral resection. In 133 of the 160 patients (83.1%) the tumor was detected by ultrasound prior to surgery. The analysis of the results revealed, however, great differences in the accuracy in the different tumor stages. In those patients where the tumor was confined to the prostate, the carcinoma was identified only in 37.5% of the cases. Especially prostatic cancer stage pT1a-b (incidental) was detected only in 3 out of 21 patients. Thus, it can be concluded that transrectal ultrasonography is not more sensitive than the rectal palpation for detection of prostatic cancer stage T1a-b.

Carcinoma↗

Effects of dietary oleic, linoleic and alpha-linolenic acids on blood pressure, serum lipids, lipoproteins and the formation of eicosanoid precursors in patients with mild essential hypertension.

Forty-four male in-patients with mild essential hypertension were randomly allocated to three groups and put on diets supplemented with 60 ml/day of olive (n = 15), sunflowerseed (n = 15) or linseed oils (n = 14), respectively, for two weeks within a blind study. In the group receiving sunflowerseed oil an increase of linoleic acid in serum lipids could be observed, whereas arachidonic and eicosapentaenoic acids appeared unchanged in serum triglycerides and even significantly lower in cholesterol esters. The subjects ingesting the linseed oil-rich diet showed an increase of alpha-linolenic acid in serum lipids, whereas arachidonic and eicosapentaenoic acids remained unchanged in serum triglycerides. In cholesterol esters, however, arachidonic acid was significantly decreased and eicosapentaenoic acid appeared increased only to a low level of significance. In the group put on the olive oil-rich regimen only a significant fall of linoleic acid was obvious in serum triglycerides. The results might indicate a defective desaturation and elongation of linoleic and alpha-linolenic acids and, consequently, a slow formation of arachidonic and eicosapentaenoic acids in patients with mild essential hypertension, which should be considered in dietary studies. After the sunflowerseed oil-rich diet a significant decrease of total cholesterol, low density lipoprotein (LDL) cholesterol and the LDL/high density lipoprotein (HDL) cholesterol ratio was found. Systolic blood pressure during a psychophysiological stress test and urinary sodium excretion appeared significantly lower after the linoleic acid-rich diet. After the linseed oil-rich diet, in addition to total cholesterol, LDL cholesterol and the LDL/HDL cholesterol ratio, serum triglycerides and lecithin cholesterol acyl transferase (LCAT) activity were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Tumor diagnosis by immunoscintigraphy with anti-CEA antibodies (Tc-99m MAK BW 431/26)].

We evaluated the clinical application of the monoclonal antibody MAb, BW 431/26, which is easy to label with Tc-99m for tumor localization. This is an anti-CEA antibody and a murine immunoglobulin (Ig G1, Isotype). We investigated patients with colorectal carcinoma (n = 14), with colorectal carcinoma recurrences (n = 24), breast carcinoma (n = 2), stomach carcinoma (n = 1), carcinoma of the urinary bladder (n = 3), lung carcinoma (n = 2) and patients with an elevated CEA level. In primary colorectal tumors (n = 14) all carcinomas were correctly localized by IS and ECT technique. In these patients the diagnosis was already known. The planar pictures showed a false negative result in 3 patients. In patients with colorectal recurrences the investigations were performed twice in 2 patients and three times in 1 patient. In these 31 ECT investigations we found 17 true positive results, 12 true negative results, 1 false positive result and 1 false negative result. The lesions were already visualized within 4 to 6 hours, but 24-hour pictures are desirable. SPECT pictures are absolutely necessary because sensitivity is considerably improved thereby. Elevated CEA levels increase the probability of a positive IS low CEA levels do not exclude positive tumor visualization. HAMA was found in only 1 patient, but follow-up investigations are indicated.

Adult↗

Isolation of overproducing recombinant mammalian cell lines by a fast and simple selection procedure.

The expression of genes transfected into mammalian cells is critically dependent on both the copy number and the site of integration. This conclusion was derived from the transfection of a plasmid containing three linked genes, which guarantees the same dose of each gene in the recipient cell clones. The selection pressure imposed by the usual concentrations of the neomycin analogue G418 or puromycin alone is low and yields cell clones with widely differing transcription rates. Time-consuming screening procedures, which are generally applied to obtain high-yield cell lines, can be obviated by the simultaneous transfer of two drug-resistance genes (neo plus dhfr, or neo plus pac). By a combined selection procedure only cells with high-level expression for the first marker will survive upon exposure to increasing concentrations of the second antibiotic. Generally, these cells also exhibit high expression levels for the non-selected gene. Many of the selected clones exhibit increased copy numbers of the respective gene but some of them owe their high productivity to a favorable position of only one or a few copies of the gene. Screening for high-yield clones using the combined selection protocol introduced here provides rapid and simple access to authentic and mutant gene products.

Animals↗

Efficient expression system for human antithrombin III in baby hamster kidney cells.

A DNA fragment carrying the enhancer of an immediate early gene of human cytomegalovirus (hCMV) was tested as a transcriptional control element by fusion downstream of a transcription unit for human antithrombin III (AT III) driven by the Simian virus (SV40) enhancer and promoter. Measurement of transient AT III expression in baby hamster kidney cells (BHK) shows that by the presence of the hCMV enhancer the synthesis of AT III is increased considerably (three to fourfold). The AT III expression vectors carrying the hCMV enhancer were used to establish stable BHK cell-lines by a new and fast G418/methotrexate selection protocol, which express up to 12 micrograms AT III/10(6) cells/24h after 40-50 days. The given system might be generally useful for the fast expression of recombinant proteins in mammalian cells, e.g. the screening of altered AT III molecules obtained by site directed mutagenesis.

Animals↗