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Biomedical subjects

M Wirth

Publications and source records attributed to M Wirth.

At least 19 recordsLinked to original sources

M-VAC versus CisCA--chemotherapy in the treatment of advanced bladder cancer.

The results of this study do not demonstrate a superiority of M-VAC chemotherapy over a modified CisCA regimen chemotherapy. M-VAC, however, proved less toxic than CisCA in terms of side effects. Neither CisCA nor M-VAC was effective as a curative treatment for patients with distant metastases. A durable complete remission of 22.5 months was seen in only 2 of the 12 patients with locally advanced tumors without distant metastases treated with M-VAC, and one of 35 months was observed in only 1 of the 6 cases with locally advanced tumors treated with CisCA chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration.

The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.

Female

Instrumental color measurement: a method for judging the appearance of tablets.

An instrumental method for the quantification of the color and the discoloration of tablets is presented. The results are not influenced by external factors and are more rapidly accessible compared with visual determination. Two of the measured parameters, lightness (delta L*) and yellowishness (delta b*) were found to reflect the changes in coloration observed in stability tests on white metoprolol tablets. Correlation studies between visual judgments and instrumental measurements are presented. The instrumental performance was carefully examined, and the results indicate that the employed instrument gives color parameters in the same range for tablet samples irrespective of whether the examined tablet surface has an engraving on it or not.

Color

Different changes of n-6 fatty acids in lipoproteins from hyperlipemic subjects after diets supplemented with n-3 fatty acids.

After diets supplemented with canned mackerel or herring, in a cross-over design, containing different amounts of long-chain n-3 fatty acids (eicosapentaenoic acid, C20:5n-3-EPA, and docosahexaenoic acid, C22(6)n-3-DHA) an increase of both EPA and DHA was confirmed in triglycerides (TG), cholesterol esters (CE) and phospholipids (PL) of very low density (VLDL) and low density lipoproteins (LDL) as well as in high density lipoproteins (HDL) from hyperlipidemic subjects. An unexpected finding was the simultaneous increase of arachidonic acid (C20:4n-6-AA) in TG and CE and its constant portion in PL of lipoproteins, whereas linoleic acid (C18:2n-6-LA) appeared lower in CE and in PL of VLDL + LDL and HDL. In general, the changes were minor after a diet supplemented with canned herring providing a lower dose of n-3 fatty acids. The results indicate dose-related changes not only of n-3 fatty acids, but also of n-6 fatty acids in serum lipids after fish diets. This different behavior of LA and AA in serum lipids might be a new aspect in the interrelations and the dietary modulation of both families of polyunsaturated fatty acids (PUFA). The accumulation of AA in neutral lipids could be linked with an elevation of prostaglandin I2, which was found apart from an increased formation of prostaglandin I3 after diets supplemented with n-3 fatty acids. The concomitant increase of prostaglandins I2 and I3 spotlights widely ignored interrelations within the eicosanoid pathway, which become evident after diets enriched with long-chain n-3 fatty acids.

Adult

Strain-specific and immunodominant surface epitopes of the P2 porin protein of nontypeable Haemophilus influenzae.

The P2 porin protein is the major outer membrane protein of nontypeable Haemophilus influenzae. Five monoclonal antibodies to P2 of four strains of nontypeable H. influenzae were developed by immunizing mice with whole bacterial cells. All five antibodies recognized epitopes on P2 in immunoblot assays of whole organism lysates, purified outer membrane, and purified P2. Competitive enzyme-linked immunosorbent assays and immunoblot assays of cyanogen bromide-digested P2 showed that two antibodies to the P2 protein of strain 1479 recognized different epitopes on the molecule. Immunofluorescence and immunoelectron microscopy demonstrated that each of the five antibodies recognized epitopes that were abundantly expressed on the bacterial surface. Analysis of 120 H. influenzae strains indicated that three of the five antibodies were reactive exclusively with the homologous strain. The remaining two antibodies were reactive with less than 3% of the strains. These studies indicate that the P2 protein expresses a highly strain-specific and immunodominant epitope on the bacterial surface. The expression of strain-specific and immunodominant epitopes on the bacterial surface may represent a mechanism by which the bacterium induces antibodies that will protect against recurrent infection by the homologous strain but will not protect against infection by heterologous strains.

Animals

The current use of interferons, interleukin-2 and tumor necrosis factor in renal cell cancer.

Cytokines such as interferons, interleukin-2 and tumor necrosis factor have been widely tested in the treatment of advanced renal cell cancer. However, the rates of objective remissions (PR and CR) are disappointing and rarely exceed 20% overall. Until now, a definitive cure of a patient with renal cell cancer treated with cytokines has not been reported in the literature. The combination of interferon-alpha and interleukin-2 in low-dose regimens seems to offer the best achievable results with the lowest morbidity of the patients in renal cell cancer. Since optimal treatment regimens are still not defined, treatment with these substances should only be carried out in prospective trials.

Antineoplastic Agents

[The value of interferons, interleukin-2 and tumor necrosis factor in the therapy of renal cell cancer].

The treatment of patients with metastasized renal cell carcinoma by biological response modifiers such as interferon (IFN), interleukin-2 (IL-2) and tumor necrosis factor (TNF) should at present only be carried out in prospective studies since there are still no generally accepted treatment regimens for these substances. In addition, one must remember that only interleukin-2 has been approved for the treatment of renal cell cancer by the Bundesgesundheitsamt (Federal Health Authority) in Berlin. Regarding interferons, IFN-alpha seems to be the most suitable substance for the treatment of renal cell cancer. However, objective response rates (almost exclusively partial responses) can only be expected in about 15% of the cases. By combining IL-2 with lymphokine-activated killer cells or IFN-alpha, objectively assessed remissions can be found in 35%. The approximate complete-response rate using this form of treatment, however, is in the range of 10%.

Carcinoma, Renal Cell

[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