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Biomedical subjects

H Gastpar

Publications and source records attributed to H Gastpar.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effect of sodium meclofenamate on radiation-induced esophagitis and cystitis.

Stumptailed monkeys (Macaca arctoides) received 2000 rad irradiation to the upper half of the esophagus and to the bladder by a 6-MEV linear accelerator. Endoscopy and biopsy was obtained from these organs weekly for 3 weeks. At the end of this period, the animals were autopsied and histopathologic examination undertaken. Sodium meclofenamate in doses of 5-20 mg/kg/day p.os was found effective in reducing or preventing radiation induced esophagitis and cystitis.

Animals↗
PubMed1984

Antineoplastic effect of the pyrimido-pyrimidine derivative: RA 233.

A number of normal and neoplastic human cell lines in culture were studied by cell count and 3H thymidine incorporation for growth inhibitory effect by the pyrimido-pyrimidine derivative RA-233 (mopidamole). There was more inhibition when the drug was added to the culture in the lag phase than in the logarithmic growth phase. There was more inhibition (particularly at low doses) of the neoplastic cell lines than of the non-neoplastic cell lines.

Antineoplastic Agents↗
PubMed1984

[Indications for tonsillectomy in childhood from the current viewpoint].

Any discussion of tonsillectomy must necessarily be based on the function and pathophysiology of the palatine tonsils. Their unique anatomic structure illustrates their main immunological function: to recognize and process the transgressors from the environment, to transfer the resulting immunological information to the entire lymphatic system and, therefore, to contribute to the immuno-defensive mechanism of the infant organism. In spite of the abundance of lymphocytes of the T- and B-type in the reticular zone of their epithelium, the tonsils seem to be dispensable because the lympho-epithelial tissue of the pharyngeal mucosa has the same immunological function and, moreover, tonsillectomy does not result in any persistent immunologic defect. However, tonsillectomy in infants up to an age of 4 years should be recommended with great reluctance if at all, since up to this age the tonsils play an important part in the immunological "learning process". Some bacterio-virological aspects are equally important for the indication of tonsillectomy in individual cases as the differentiation between chronic and recurrent tonsillitis. In the treatment of the secondary cervical lymphadenitis, too, such differentiation is mandatory. Chronic tonsillitis in terms of a "focal disease" is a rare event in infants, and tonsillectomy is recommended only in such exceptional cases where recurrent streptococcal infections resulted in rheumatism or glomerulonephritis.

Age Factors↗
PubMed1983

The inhibition of cancer cell stickiness by somatostatin.

We employed a test model, which we had developed for the investigation of platelet adhesiveness and aggregation in vivo. Our experiments demonstrated that somatostatin is not only able to dose-dependently inhibit the stickiness of i.v. injected Walker 256 carcinosarcoma cells to the vascular endothelium of the rat mesentery and the drastic, immediate reduction of platelet count in venous blood, but also to significantly reduce the rate of instantly occurring terminal tumor cell embolism of the lung. These actions may be explained as being mediated via an inhibition of platelet adhesion and aggregation to circulating cancer cells. Because some oral antidiabetics showed a similar but weaker effect in our test system (Gastpar et al. 1982), it should be examined as to whether the in vivo inhibition of platelet adhesiveness and aggregation of the investigated compounds are mediated by a somatostatin release from the pancreas.

Animals↗
PubMed1983

[Modification of metastasis formation by inhibition of platelet aggregation. Experimental and clinical results].

Our clinical study to prevent relapse and metastases in several sarcomas and malignant lymphomas of the head and neck region with a long-term treatment with mopidamole was initiated in 1972 because the pyrimido-pyrimidine derivative was shown to inhibit platelet aggregation in vivo and to increase significantly the circulation time of intravenously injected, 32P-labelled Ehrlich ascites tumour cells in mouse blood. The aggregation of platelets to circulating tumour cells and their subsequent adhesion to vascular endothelium in turn appeared to be part of the early stages of the metastatic process. It seems, however, that other related mechanisms are also involved in the clinical results obtained. Mopidamole, as other related derivatives, probably inhibits platelet aggregation by inhibition of PDE-induced decomposition of cAMP and may stimulate the synthesis and/or release of prostacyclin from the vessel wall which in turn activates adenylate cyclase involved in cAMP synthesis. The latter mechanism was definitely shown only for the related pyrimido-pyrimidine derivative dipyridamole, the methyl-xanthine derivative pentoxifylline and the methyl-pyrazoline derivative nafazatrom. The increase of cAMP levels by mopidamole results in an inhibition of 3H-thymidine incorporation into human neoplastic cells and a direct inhibition of its mitotic rate. The adding of mopidamole to a culture of a human promyelocytic leukemic cell line promotes a reverse transformation of the malignant cells to normal which appears to be a permanent phenotypic change. Furthermore, mopidamole was shown to diminish significantly spontaneous lung metastases in syngenic Wilms' tumor (nephroblastoma) of the rat, the C1300-neuroblastoma of the mouse and the HM-Kim mammary carcinoma of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

The inhibition of cancer cell stickiness, a model for investigation of platelet aggregation inhibitors in vivo. Effect of the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB180, as well as the carboxylic acid derivative, meglitinide.

Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.

Animals↗
PubMed1982

Prophylaxis of seasonal allergic rhinitis with a new antihistaminic drug.

The efficacy and tolerance of alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) 60 mg b.i.d. were investigated in 25 patients in an open clinical trial lasting six months. Terfenadine was applied prophylactically against seasonal allergic rhinitis. Terfenadine produced no change in body functions or laboratory values (heart rate, respiratory rate, body temperature, and blood pressure). In this long-term study terfenadine was tolerated very well. All patients were free of severe side effects. No attacks of allergic rhinitis were seen due to the potent prophylactic efficacy of terfenadine. In this study terfenadine showed good efficacy and tolerance similar to that reported by former clinical studies. It should be emphasized that sedation was not observed with terfenadine.

Adolescent↗
PubMed1982

Comparative study of the efficacy and tolerance of terfenadine and clemastine in patients with seasonal allergic rhinitis.

The efficacy and tolerance of alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxyphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) and clemastine were investigated in 20 patients in a single blind, randomized clinical study of three months duration. A total of 15 patients was treated with terfenadine (2 X 60 mg/day), and five patients were treated with clemastine (2 X 1 mg/day). Clemastine and terfenadine were applied as a prophylaxis against seasonal allergic rhinitis. No change in body function or in laboratory values (heart rate, respiratory rate, body temperature, and blood pressure) was seen after antihistamine treatment. Two patients taking clemastine reported moderate sedation. No sedative effects were reported in the terfenadine group. Two patients in the clemastine group and one patient in the terfenadine group had an attack of allergic rhinitis during the study. In this study terfenadine showed good efficacy and tolerance similar to that reported by former clinical studies. It should be emphasized that sedation was not observed with terfenadine.

Adolescent↗
PubMed1982

Studies on platelet aggregation inhibitors in vivo. X. Relationship to thrombolysis.

Human labeled fibrin clots were inserted into femoral veins of stumptailed monkeys (Macaca arctoides). Thrombolysis was slightly increased by treatment with the platelet aggregation inhibitor pentoxifylline. This agent significantly potentiated the thrombolytic effect of urokinase activated human plasminogen. Pentoxifylline was also found to release plasminogen activator activity into the circulation.

Animals↗
PubMed1982

Study of platelet aggregation in vivo. IX. Effect of nafazatrom on in vivo platelet aggregation and spontaneous tumor metastasis.

Nafazatrom (Bay g 6575) was explored for its ability to inhibit platelet aggregation. In vitro, it had no effect on ADP, serotonin, epinephrine, or collagen induced platelet aggregation in platelet rich plasma of monkeys. On the other hand, in vivo it was a powerful inhibitor of ADP induced platelet aggregation as measured by the in vivo platelet aggregation recording instrument described previously (Ambrus et al., 1976). This effect was potentiated by dipyridamole. On the other hand, following parenteral administration of Bay g 6575, no ex vivo inhibition was noticed of ADP, serotonin, epinephrine, and collagen induced platelet aggregation. The hypothesis was presented that Bay g 6575 acts by increasing prostacyclin synthesis and/or release or interferes with its decomposition. This may explain in vivo activity; rapid decomposition may explain inability to demonstrate ex vivo activity. This also explains potentiation by the phosphodiesterase inhibitor dipyridamole. Bay g 6575 also was highly effective as a platelet aggregation inhibitor in monkeys after oral administration. In mice, Bay g 6575 increased circulation time of intravenously injected polyploid Ehrlich ascites tumor cells. In Furth-Wistar rats implanted with Furth-Columbia Wilms' tumor, in A/J mice implanted with C1300 neuroblastoma and in Wistar rats implanted with SMT-2A (Kim) breast cancer, Bay g 6575 significantly reduced spontaneous pulmonary metastasis. On the other hand, no effect was seen in the metastatic rate of NIH renal adenocarcinoma in BALB/cCr mice.

Adenocarcinoma↗
PubMed1982

Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors: a possible approach to metastasis prevention.

Abnormal platelet aggregation on circulating and lodged cancer cells may play an important role in the early stages of metastasis formation. The immediate drop in the number of circulating platelets following intravenous injection of Walker-256 carcinosarcoma cells in rats represents the experimental counterpart of the morphologic finding of tumor cells associated with tumor clusters in the pulmonary arterioles and capillaries.

Animals↗
PubMed1981

New aspects of the pathogenesis of atherosclerosis: possible approaches to prevention and treatment.

New techniques in cell biology and recent advances in rheology have opened up fresh perspectives in the understanding of the pathogenesis of atherosclerosis. There is now an increasing amount of experimental evidence to support the hypothesis that arterial thrombi are the first stage in atherogenesis in the context of endothelial lesions and not merely secondary factors without any causal significance. Factors influencing platelet aggregation and adhesiveness are discussed, and the animal and clinical studies carried out with the platelet aggregation inhibitor pentoxifylline and its effects on the microcirculation are reviewed.

Animals↗
PubMed1981

Effect of phosphodiesterase inhibitors on platelet aggregation and tumor metastasis.

Recent studies suggest a relationship of platelet aggregation to metastatic spread of neoplasia. In the present experiment pentoxifylline appears to be a highly effective platelet aggregation inhibitor: a dose-response curve is apparent in monkey between 6 and 24 mg/kg i.v. Besides pentoxifylline significantly reduces metastasis rates in Wilms' tumor and neuroblastoma in rodents: 18 mg/kg significantly increase polyploid Ehrlich ascites tumor cell circulation time; on the contrary it has no effect on metastasis in the NIH renal adenocarcinoma. It is thus possible that platelet factor related blood coagulation processes play a different role in the fate of these tumor cells. This may be related to cell membrane characteristics. Phosphodiesterase inhibitors alter membrane fluidity and cell deformability of cancer cells which may pass the microcirculation easier and are less likely to settle and form metastases. Agents with both platelet aggregation inhibitory and red cell deformability increasing effect may find a place in our therapeutic armamentarium in oncology.

Adenocarcinoma↗