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Biomedical subjects

F Wagner

Publications and source records attributed to F Wagner.

At least 127 records · Page 7Linked to original sources
PubMed1990

Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (Echinacin) and thymostimulin.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

Adjuvants, Immunologic↗
PubMed1990

Overexpression of protein kinase C beta 1 is not sufficient to induce factor independence in the interleukin-3-dependent myeloid cell line FDC-P1.

To examine whether overexpression of protein kinase C (PKC) is sufficient to allow for factor-independent growth in hematopoietic cells, we used a recombinant retroviral expression vector system to introduce a cDNA encoding the beta 1 isoform of the PKC gene into IL-3-dependent cells FDC-P1. Cell lines were generated which contained up to 24-fold increases in PKC activity. Analysis of these cell lines demonstrated that PKC activation does not play a significant role in IL-3-mediated growth control, as evidenced by the following: (1) IL-3 addition to either overexpressor cell lines did not induce morphologic changes whereas activators of PKC stimulated cellular clumping; (2) early passage FDC-P1 cells, either carrying normal or elevated levels of PKC, were not stimulated to grow by activators of PKC; and (3) addition of phorbol esters or bryostatin 1 to these cells markedly decreased the levels of PKC without affecting the ability of these cells to grow in IL-3. Therefore, we suggest that IL-3 mediated growth occurs through pathways other than involving PKC.

Bryostatins↗
PubMed1989

Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma.

Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.

Cells, Cultured↗
PubMed1989

Monoclonal antibodies against epitopes on ganglioside GD2 and its lactones. Markers for gliomas and neuroblastomas.

Monoclonal antibodies (mAbs) BW 625 and BW 704, of the IgG3 isotype, bound to immunochemically indistinguishable epitopes on ganglioside II3(Neu-Ac)2-GgOse3-Cer. Despite this fact the mAbs showed a differential binding pattern on human glioma cell lines i.e. immunohistochemical data indicate that the detected epitopes are not identical. Furthermore, either mAb is able to mediate the antibody-dependent cellular cytotoxicity reaction (ADCC) and the human-complement-dependent cytotoxicity reaction (CDC) with epitope-expressing tumor cells. All cryopreserved tissue specimens from gliomas and neuroblastomas were immunohistochemically stained, whereas the other small round cell tumors of childhood, as well as melanomas and small-cell lung carcinomas, were essentially negative. Positive staining of normal cryopreserved tissues was restricted to amyelinic axons, Hassal's bodies and some connective tissue fibers in thymus and the tegumentary epithelium of skin. The high selectivity of mAb BW 704 for gliomas and neuroblastomas, the lack of cross-reactivity with major tissues and the strong ADCC and CDC potential argue for the use of mAb BW 704 in immunotherapy of neuroblastomas and gliomas.

Antibodies, Monoclonal↗
PubMed1989

Evaluation of the beta-adrenoceptor blocking activity of the Class Ic antiarrhythmic drug diprafenone in man.

The beta-adrenoceptor blocking activity of the new Class Ic-antiarrhythmic drug diprafenone has been determined in man in comparison with that of propranolol, using the standardized isoproterenol test. Following placebo, the dose of isoproterenol which increased the heart rate by 25 beats.min-1 (CD25) was 0.84 (0.1-2.72) micrograms (median and range). Two hours following single oral doses of 200 mg diprafenone (3.61 micrograms; 1.53-44.15) or 40 mg propranolol (16.06 micrograms; 9.15-27.04) significantly higher CD25-values were found. The affinity constants for the beta-adrenergic receptors calculated on the basis of free drug in the plasma were similar for propranolol and diprafenone (2.79 vs. 2.60 nM-1, respectively). Thus, diprafenone showed a definite degree of beta-blocking activity in a clinically relevant range of plasma concentrations.

Adrenergic beta-Antagonists↗
PubMed1989

Pharmacokinetic characterization of the antiarrhythmic drug diprafenone in man.

The pharmacokinetics of the antiarrhythmic drug diprafenone have been investigated in 6 healthy volunteers following single intravenous (50 mg) and oral doses (50 and 150 mg). Diprafenone was mainly eliminated by metabolism in the liver. Following i.v. infusion of 50 mg diprafenone, the terminal half-life of elimination was 1.50 h, the volume of distribution at steady-state was 1.23 l.kg-1, and the free fraction in plasma was 1.68%. Mean total plasma clearance was 741 ml.min-1.70 kg-1, which approaches normal liver blood flow after correction for the blood/plasma concentration ratio. Thus, diprafenone can be classified as a high extraction drug. Following oral administration, a dose-dependent increase in bioavailability from 10.9 (50 mg dose) to 32.5% (150 mg dose) was observed. The data suggest that diprafenone is subject to saturable hepatic first-pass metabolism.

Administration, Oral↗
PubMed1989

[Microinvasive stage Ia cancer of the uterine cervix--results of a multicenter clinic based analysis].

A retrospective multicentre study to investigate diagnosis, treatment and end results of treatment of cervical cancer stage Ia, was carried out in 6 departments of gynaecological oncology. After reclassification by a reference pathologist, among the 936 cervical cancer cases primarily diagnosed and treated as stage Ia between 1970 and 1980, only 530 (56.6%) met the criteria of microinvasive cancer stage Ia. Misclassifications concerned all participating centres with statistically significant differences amongst them. Overdiagnosis (reference diagnosis only CIN I-III, 42.5%) was more frequent than underdiagnosis (reference diagnosis stage Ib--0.9%). In comparison to 1970-74, in the period 1975-80 a significant increase of cases detected asymptomatically (86.5%) was observed. The percentage of cases primarily diagnosed by cone biopsy, also increased significantly and amounted to 71.2%. Patients with cervical cancer stage Ia were most frequently treated by surgery alone (93.2%). Radiotherapy alone did not play any important role (5.7%). There were only a few cases treated by combined surgery and radiotherapy (5.7%) with a decreasing trend over time. Women under the age of 45 years were significantly more frequently treated by the conservative method (cone biopsy, simple hysterectomy) than older ones, without any significant relation between depth of invasion and radicality of treatment. A total of 19 (14 local, 5 lymph node) recurrences were diagnosed between 9 and 110 months after primary treatment. Local recurrences could be observed more frequently after limited than extended treatment. There was no significant relation between depth of invasion and frequency of recurrences, but the latter were significantly increased in cases with histologically proven invasion of blood or lymph vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Substance P modulates lymphokine activities in supernatants of cultured human duodenal biopsies.

A duodenal biopsy culture technique was used to investigate the effect of substance P on lymphokine secretion by the human gut associated lymphoid tissue. Duodenal biopsies of 7 healthy volunteers were cultured in 1 ml medium each with Pokeweed mitogen (1 microgram/ml) for 4 days at 37 degrees C. Substance P (SP) was added in concentrations ranging from 10(-12) M to 10(-6) M. Media were changed every day. Interleukin (IL)-1 beta, IL-2 and IL-2-receptor activities were determined by means of specific ELISAs. Values were referred to 5 mg biopsy weight and expressed as per cent change of basal Pokeweed mitogen-pulsed supernatant activities. 10(-8) M and 10(-6) M SP led to a decrease of IL-1 beta activity (78 +/- 13.9% and 62.8 +/- 17.1%, respectively, alpha = 0.01 each). In contrast, 10(-8) and 10(-10) M SP showed an increase in IL-2 activity up to 182.9 +/- 94.5% and 295.6 +/- 144.7%, respectively. 10(-6) M and 10(-8) M SP enhanced IL-2 receptor activities by 81.5 +/- 70% and 40.9 +/- 11.8%, respectively (alpha = 0.05). The present data demonstrate for the first time distinct SP-mediated effects on lymphokine activities in supernatants of cultured human duodenal biopsies.

Adjuvants, Immunologic↗
PubMed1988

Quality of life in patients with inflammatory bowel disease.

To investigate the effect of inflammatory bowel disease (IBD) on the quality of life, we interviewed 43 patients with ulcerative colitis (UC) and 54 with Crohn's disease. Patients identified frequent and important problems in five areas. Primary bowel symptoms, systemic symptoms, and altered emotional function were common; functional and social impairment were less frequent. Systemic symptoms such as fatigue were more prevalent in patients with Crohn's disease. Apart from primary bowel complaints, patients seldom volunteered other facets of quality of life impairment; this was particularly true for impairment of emotional function. We conclude that despite troublesome intestinal and systemic symptoms, most patients with IBD avoid major disruption in work and personal lives. Physicians must inquire specifically about emotional problems relating to IBD; in particular, fear of surgery is important to address. Psychosocial interventions should be targeted to those patients with problems in this area.

Adult↗
PubMed1988

[Combined ischiatic/3-in-1-block. II. 1 percent mepivacaine HCl versus 1 percent CO2 mepivacaine].

In a prospective randomized study on 26 patients, the clinical effectiveness CO2-mepivacaine 1% (group 1, 13 patients) and mepivacaine HCl 1% (group 2, 13 patients), was tested in patients having a sciatic-femoral block for surgical procedures of the lower extremity (20 ml for sciatic and 30 ml for 3-in-1 block). Blood levels of mepivacaine were determined for up to 90 min in 8 patients from each group. The onset of sensory and motor blockade was slightly earlier (4-5 min) with CO2-mepivacaine than with the hydrochloride (5-6 min). The time to complete block was 8-11 min with CO2-mepivacaine and 11-12 min with mepivacaine HCl. There was a relatively large variance in intensity of blockade that was not necessarily related to the drug employed, but can be explained by individual factors and possibly by slight differences in blocking technique. Nevertheless, the rate of unsuccessful blockade was remarkably higher (38%) with the hydrochloride than with CO2-mepivacaine (7.7%). Determinations of blood levels did show the expected earlier peak (after 20-30 min) and higher blood-levels (means 3.8 micrograms/ml at 30 min) with CO2-mepivacaine 1% as compared to mepivacaine HCl 1%: 2.9 micrograms/ml at 30 min and 3.4 micrograms/ml at 45 min.

Carbon Dioxide↗
PubMed1988

[Combined sciatic/3-in-1 block. III. Prilocaine 1% versus mepivacaine 1%].

In a randomized, double-blind study, the efficacy of prilocaine 1% (group 1, 30 patients) was compared to mepivacaine 1% (group 2, 30 patients). All patients had a combined sciatic/femoral block for surgery of the lower extremities; a tourniquet was applied in each case. In each patient the block was done using 50 ml of a 1% solution of local anesthetic: 20 ml for the sciatic and 30 ml for the 3-in-1 block. The time to onset of sensory block was approx. 4 min in both groups; the onset of motor blockade averaged 6 min and after 10-12 and 15 min sensory and motor blockades, respectively, were complete. On the average, patients were pain-free for 254 min with prilocaine and 267 min with mepivacaine. Four of 30 patients (= 13%) in group 1 an 6 of 30 patients (= 20%) in group 2 had an unsatisfactory blockade and had to be supplemented by analgesics or general anesthesia. The finding of a significant correlation between the voltage necessary for stimulation and the efficacy of the blockade underlines the importance of correct stimulation when identifying the nerves.

Adult↗
PubMed1988

[Combined sciatic nerve/3-in-1 block. I. Dose determination for CO2-lidocaine 1.1%].

The goal of this open-labeled clinical study on 30 patients was to find out which dosage of CO2-lidocaine 1.1% (= lidocaine HCl 1%) would provide clinically acceptable analgesia for surgical procedures on the lower extremities under combined sciatic-femoral block. A first group of 5 patients was given a dose of 330 mg = 30 ml (15 ml to block the sciatic nerve and 15 ml for the 3-in-1 block), the maximum dose allowed by the manufacturer. This dosage did not result in any degree of satisfactory block and all patients had to be operated upon under general anaesthesia (GA). In a second group of 15 patients, a dose of 440 mg = 40 ml was given (sciatic nerve: 17 ml; 3-in-1 block: 23 ml). This dosage gave much better results, but 4 of 15 patients still needed light GA for supplementation. Only in the third group of 10 patients, who were given 550 mg = 50 ml (sciatic nerve: 20 ml; 3-in-1 block: 30 ml) was a clinically acceptable success rate achieved; there was only 1 patient who needed light GA for supplementation. In group I (330 mg) only partial sensory blockade was achieved (after approx. 5 min); the femoral and lateral femoral cutaneous nerves could not be blocked in any patient, and motor blockade was present in only 1 patient. In group 2 (440 mg) the onset of sensory block began after 5 min, was complete by 11 min, and in 6 of 15 patients (= 40%) motor blockade was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.

A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.

Angina Pectoris↗