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Biomedical subjects

U Ganzinger

Publications and source records attributed to U Ganzinger.

At least 37 records · Page 2Linked to original sources

Influence of ethylene-2,2'-bis (dithio)bis(ethanol) on certain human in vitro and in vivo lymphocyte functions.

The influence of in vivo or in vitro exposure of human lymphocytes to ADA 202-718 (ethylene-2,2'-bis (dithio) bis (ethanol)) was tested. Evaluated were spontaneous, lectin, or alloantigen-induced proliferation as well as the release of IFN-alpha, gamma and of neopterin. The spontaneous cell mediated lysis (NK lysis) of K 562 tumor targets was also assessed. In vitro exposure to ADA 202-718 slightly enhanced lectin and alloantigen-induced human lymphocyte proliferation. IFN-gamma release was also slightly increased. These parameters were not clearly affected by in vivo treatment with ADA 202-718. In vitro and in vivo-treatment with this drug did not affect spontaneous lymphocyte blastogenesis. Statistically significant effects, however, were seen when NK activity was assessed. Preincubation of either effector or target cells with ADA 202-718 as well as in vivo treatment caused an increase of NK lysis. When these results obtained with human cells were compared with those previously seen in a murine system, immunostimulatory activity of ADA 202-718 was more pronounced in the murine system.

Biopterins↗

Influence of endotoxin on the distribution of cephalosporins in rabbits.

The concentration: time courses of six different cephalosporins were studied in serum and interstitial fluid from issue cages after intravenous injection in normal and endotoxaemic rabbits. Circulatory and metabolic changes induced by endotoxin were similar to the altered organ function observed in patients with septicaemia. A significant shift of drug fractions, increase in the volume of distribution and prolonged mean residence times were observed in this model with ceftazidime, ceftriaxone and CPW 86-363, and were the result of specific changes in the peripheral compartment. The opposite findings were observed with cefotaxime, while latamoxef and cefoperazone resulted in no changes.

Animals↗

The utility of diffusion chambers as models for the description of drug disposition.

Tissue cages were employed to explore the diffusion processes of several cephalosporins into extravascular fluids. Concentrations of cefotaxime in serum and in subcutaneous chambers increased proportionally to the amount of the drug injected. Administration of single equal doses of cephalothin, cephaloridine and cefotaxime resulted in different concentration-time courses in the serum and in diffusion chambers. These observations suggest that diffusion chambers are linked to the tissue at the implantation site. None of the classical compartmental approaches can be applied to evaluate the kinetics of drug diffusion into tissue cages. Correlations of total or non-protein bound drug concentrations in tissue cages to those in the peripheral compartment assumed concentration and time dependent diffusion processes. No specific diffusion constant based on the law of Fick could be derived for the diffusion chambers used in this study. Concentration-time courses in serum and interstitial fluid can be simultaneously evaluated according to pharmacokinetic-pharmacodynamic models. Based on the equation describing the effect site this model can be used to simulate drug concentrations in tissue cages by varying the dose size or the dose interval.

Analysis of Variance↗

Allylamines: topical and oral treatment of dermatomycoses with a new class of antifungal agents.

A new class of synthetic antifungal agents, characterized by an allylamine function as the essential structural feature, is reviewed. Two members of this class, identified by the generic name Naftifine and the code number SF 86-327 respectively, which were selected for further development from among several hundred analogous, are described in greater detail. As a class, the allylamines are highly active against dermatophytes and moulds, and moderately active against yeasts. Naftifine has been developed as an agent for the topical treatment of dermatomycoses, while SF 86-327 is under development in both topical and oral formulations, being the first orally applicable antifungal agent with a primarily fungicidal mode of action.

Administration, Oral↗

Pharmacokinetics of cephalosporins in normal and septicemic rabbits.

The differences in the pharmacokinetics of cefotaxime, moxalactam, and CPW 86-363, a new expanded-spectrum cephalosporin, were studied in healthy rabbits and in rabbits infected intravenously with Streptococcus pneumoniae. The pharmacokinetic analysis of concentration-time courses in the sera of infected animals according to a two compartment-model evidenced a clear decrease of drug fractions in the central compartment but enhanced drug fractions in the peripheral compartment. The shift was more pronounced in animals which received CPW 86-363 (60%; P less than 0.05) than in those which received cefotaxime (20%) or moxalactam (5%). Corresponding increases in drug concentration were observed in soft tissue interstitial fluid; therefore, the areas under the curve and mean residence times in the soft tissue interstitial fluid of infected rabbits were prolonged. The shift of drug fractions from the central compartment to other body fluid compartments during infection was thought to be due to cardiovascular changes associated with fever. No changes in serum binding of the three drugs were found during the course of the infection. The quantitative differences in the extent of altered distribution properties of the drugs might be due to variations in the physicochemical properties of the drugs.

Animals↗

The preparation and use of a carrier-bound acceptor for the determination of sialyl transferase activity in serum.

Agarose-bound asialofetuin functions as an insoluble sialyl group acceptor in a simplified assay for sialyl transferase (CMP-neuraminate: D-galactosyl-glycoprotein N-acetylneuraminyl transferase; EC 2.4.99.1) in serum. Since sialyl transferase levels in serum are elevated in a large number of malignant conditions, the simplified assay is of use for clinical monitoring in tumour therapeutic programmes.

Asialoglycoproteins↗

The diltiazem-digoxin interaction.

To study the interaction between the calcium antagonist diltiazem and digoxin, a randomized crossover trial under steady-state conditions was carried out in 24 healthy male subjects. Diltiazem with digoxin induced an average increase of steady-state plasma digoxin concentration and AUC over 48 hr of 22.4%. This is caused by the prolongation of elimination t1/2 from 36.2 +/- 11.2 to 44.5 +/- 11.5 hr (means +/- SD) and the impairment of total digoxin clearance, dropping from 146.6 +/- 37.9 to 107.9 +/- 18.4 ml/min. Average reduction in renal clearance (from 102.1 +/- 35.5 to 85.5 +/- 42.7 ml/min) was not statistically reproducible. Apparent volume of distribution was not relevantly altered. Diltiazem kinetics did not change significantly when digoxin was concurrently given.

Adult↗

[Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy].

Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours. Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic. In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals. The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001). This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment. Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug. Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases. Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration.

Adult↗

Acute cardiac toxicity in patients after doxorubicin treatment and the effect of combined tocopherol and nifedipine pretreatment.

In two groups of female patients with metastatic breast cancer who had all been pretreated with doxorubicin (350 mg/m2), acute cardiac effects following i.v. doxorubicin bolus injection (60 mg/m2) were recorded on the basis of systolic time intervals (STI). In six patients who received doxorubicin only the ratio between the heart-beat-corrected preejection period and left ventricular ejection time (PEPI:LVETI) as well as the PEP index were found to be significantly increased with a peak at 6 h following drug infusion (P less than 0.001). Another six patients received an identical chemotherapeutic regimen and, in addition, a combination of tocopherol (200 mg i.m. 6 h before treatment) and nifedipine (60 mg p.o. daily from 2 days before doxorubicin infusion). In the pretreatment group, the PEPI:LVETI ration and PEP index remained unchanged during the posttreatment period. Pharmacokinetic analysis of drug concentrations in the plasma revealed a significantly accelerated distribution and elimination of doxorubicin after combined tocopherol and nifedipine pretreatment, although no statistically significant differences could be found in calculated drug levels in the peripheral compartment between both treatment groups. Our results indicate that acute cardiac reactions reflected by changes in STI values can be prevented by combined tocopherol and nifedipine pretreatment.

Adult↗

Studies in man with a cold-recombinant live influenza B virus vaccine.

A cold recombinant live influenza B virus vaccine was tested in man. In comparison to a placebo, reactogenicity attributable to virus infection was slight or moderate. No revertant viruses were shed, and there was no evidence of transmission to the placebo group who were housed in close contact with the vaccinees. Serological responses to initial inoculation were moderate; 60% of vaccinees showing twofold increases in serum hemagglutination inhibition (HAI) titers gave a geometric mean titer (GMT) of 1:13. Three weeks after the first vaccination, both the vaccine and the placebo group were revaccinated with homologous live virus vaccine. The group previously given vaccine was resistant to reinfection as judged from clinical reactions and virus shedding and the GMT increased only slightly to 1:16.3. In contrast, the former placebo group responded; mild symptoms were seen, the majority shed viruses and 50% showed twofold increases in serum HAI titers to a geometric mean titer of 1:17.4.

Adult↗

[Developments in the serological diagnosis of malignant diseases].

The present study gives an evaluation of carcinoembryonic antigen (CEA), macrophage electrophoretic mobility test (MEM), sialyltransferase, galactosyltransferase isoenzyme (SGT), ribonuclease and reverse transcriptase as diagnostic aids in malignant diseases. CEA and sialyltransferase are of certain value in the monitoring of cancer, as their values in the serum may rise before progression of disease or relapse. Both tests are not reliable parameters in the early diagnosis of malignancy. Our results with regard to the MEM test have not proved in any way useful in the diagnosis of cancer. Our preliminary results appear to indicate that, provided further simplification of the method can be achieved, SGT isoenzyme determination seems to be a better means of diagnosing cancer. In view of inherent-methodological difficulties reverse transcriptase has, at present, no clinical application in the diagnosis of cancer.

Carcinoembryonic Antigen↗

[Serum concentration measurements for the monitoring of anti-arrhythmic therapy with lidocaine].

Repeated measurements of lidocaine serum levels during antiarrhythmic treatment were performed by enzyme-immunoassay (EMIT) in 16 patients with acute myocardial infarction. In 12 cases the frequently employed standard dose (100 mg i.v. followed by infusion of 2 mg/min) was not sufficient to reach optimum lidocaine (2-5 mg/l) during the first 2 hours. In this period 6 patients had persistent ectopic beats and required additional bolus injections and increased infusion rates. Lidocaine elimination was delayed in patients with heart failure, which led to potentially toxic drug accumulation in 3 instances. This study indicates the need for individual adaptation of lidocaine dosage in patients with myocardial infarction, especially where left ventricular function is impaired. Monitoring of serum lidocaine levels by a rapid and reliable assay such as the EMIT system may greatly facilitate this task.

Adult↗

Serum sialyltransferase levels as a parameter in the diagnosis and follow-up of gastrointestinal tumors.

Serum sialytransferase (SST) levels were determined in patients with various gastrointestinal cancers at different clinical stages. These SST values are significantly elevated over normal healthy controls, and a correlation was observed beteen tumor stage and SST activity. While SST levels rise in patients with increasing tumor burdens, they revert to normal in patients with undetectable tumor tissue after radical surgery. In a group of patients, carcinoembryonic levels were determined along with SST values, and both sets of data were correlated to the clinical diagnoses. The usefulness of SST determinants in the diagnosis and follow-up of gastrointestinal tumors is discussed.

Adult↗

Sialyl transferase activity: a serum enzyme marker in the follow-up of cancer patients.

Clinical evaluation of serum sialyl transferase as a diagnostic tool in malignant disease has shown that there is a strong correlation between enzyme activity and extent of tumor tissue. Thus, patients with large tumor masses show higher enzyme activity than patients with small tumors or in remission. Furthermore, the surgical removal of tumor tissue results in a decrease of enzyme activity to the normal range. The values remain low until metastases recur; this is connected with a new increase in enzyme activity. It has also been shown that successful chemotherapy corresponding to tumor reduction is reflected in lower values. We are thus led to believe that sialyl transferase is a relevant diagnostic blood parameter in the follow-up of cancer patients.

Breast Neoplasms↗

[The clinical application of serum sialyl transferase determination as criterion of malignant transformation of cell surface structure (author's transl)].

The activity of a specific glycosyl transferase, namely, sialyl transferase was determined in a sera of patients with malignant disease. Increased serum sialyl transferase activity was observed in a high percentage of examined cases. The serum enzyme activity was also correlated to the clinical state of the patients and was found to depend on the tumor size. The enzyme activity decreased following surgical removal of the tumor mass and increased an appearance of metastases. These findings may be the basis for possible clinical application in the follow-up of patients with malignant disease, because the diagnostic value of serum sialyl transferase determination is greater than that of other serum analyses.

Bronchial Neoplasms↗

[A comparison of serum phosphohexose isomerase and sialyl transferase activities in patients with malignant disease].

The diagnostic value of serum sialyl transferase, phosphohexose isomerase and lactate dehydrogenase determinations is discussed in respect to patients with malignant diseases. It was found that 80 % of the investigated cases showed an increase in serum sialyl transferase activity. Phosphohexose isomerase was elevated in 46.6 % and lactate dehydrogenase in 23.3% of the cases. The serum sialyl transferase activity was within the normal range in 13.3% of the patients. It is concluded that although the serum sialyl transferase activity is of great diagnostic significance in cases of suspected malignancy, total reliance cannot be placed on the determination of this sole parameter, but only in conjunction with others.

Breast Neoplasms↗