Biomedical subjects
Publications and source records attributed to E Paul.
Three myosin isoforms, two of smooth muscle and one of cytoplasmic origin, were found in porcine brain by Western blotting analysis with antibodies specific for smooth and cytoplasmic myosins. The smooth muscle isoforms comprise at least 30% of the total myosin present. Brain tissue is therefore not a suitable source for the isolation of pure cytoplasmic contractile proteins.
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Forty patients with chronic urticaria were treated with terfenadine or astemizole in a randomized double-blind study. The intensity of the symptoms was quantified and documented daily by the patients. Both antihistamines had a clear effect on the intensity of the pruritus and the severity of the wheals. Neither astemizole nor terfenatine produced any sedative side effects.
The objective of this double-blind study, which is part of a multicenter study, was to determine whether terfenadine (120 mg once daily) has similar efficacy and tolerability to the standard dosage of 60 mg twice daily in the treatment of chronic urticaria. Forty-one patients were randomly allocated to two parallel groups and treated for 2 weeks with either regimen. Evaluation of efficacy was based on rating scales for investigator and patient. Primary endpoints were itch, number of wheals, wheal size, and the overall rating of efficacy. A similar improvement was seen in all variables. There were no statistically significant differences between groups. Both treatments were well tolerated.
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305 patients suffering from chronic urticaria were tested according to a special program, which combined the common allergologic skin testing with the searching for foci of inflammation. The central part of the diagnosis, however, are oral provocation tests during potato/rice diet with non-steroidal antiphlogistic agents and so-called food additives as well as "natural" salicylates. Acetylsalicylic acid and indomethacin most frequently caused reactions of intolerance, whereas all of the patients tolerated paracetamol (500 mg) without any reactions. With food additives and "natural" salicylates, intolerance reactions were rare. In our patients, skin testing only rarely led to any relevant results; the search for foci, instead, led to numerous findings, which, however, seemed not to have much influence on the further course of the disease. Apparently, the healing rate was neither influenced by the reactions of intolerance, nor the fact whether the patient had got a proper diet or not; we suggest, therefore, that the interpretation of the test results should be reconsidered.
On the basis of serial X-ray pictures, we studied the growth dynamics of 50 pulmonary metastases (PM) in 18 patients suffering from malignant melanoma. As all the PM investigated showed exponential growth, we concluded that the PM of malignant melanoma increased according to a continuous growth rate during the period of investigation. By regression analysis, the mean tumor duplication time was calculated in 28 metastases. The tumor duplication time varied considerably (from 9 to 298 days), the majority ranging between sexes: The mean value in male patients was 35 days, in females 36 days. Assuming a constant growth dynamics of the metastases over the entire period of observation, the exact time at which the metastases theoretically started to grow as single cells was calculated by means of regression analysis. The hypothetical lifetime of the metastases is extremely long and reaches far back into the past. Thus it may be assumed that in many cases metastatic growth begins a long time before the primary tumor is surgically removed.
Anamnestic data of 668 patients suffering from malignant melanoma were statistically evaluated. More than half of the patients had noticed a "mole" at the site where the melanoma was subsequently found. More than a third of the patients guessed that this mole had always been there, and an additional 15% were of the opinion that the mole had been present since childhood. About a third of the patients stated that the lesion had existed for more than 20 years. About 45% of them had been aware of it for between one and 20 years. Only 21.5% had not noticed any pigmented spot until less than one year before the diagnosis of melanoma. From the data, we conclude that in about 35% of the cases the pigmented area had first been noticed before puberty; in 49% of the cases, the lesion had not been observed until the patient's 36th year of age. Once the patients became aware of the growing development of the mole, 62% of them sought medical advice within one year. The other patients waited longer, 8.7% of them even more than 5 years, before having it removed. In the majority of the cases, the patients' attention was drawn to the malignant growth by changes in size and thickness. In 40% of the cases, changes in color were noted. The "classic" signs of alarm such as itching and bleeding were reported in 29.2% and 34.9% of the cases, respectively.
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The effects of the H-1 receptor blocker terfenadine and the H-2 receptor blocker ranitidine have been experimentally tested in wheals induced with histamine and suxamethonium chloride. Ranitidine alone in the standard and a four-fold higher dose did not notably reduce the size of the wheal and flare as compared to placebo. As expected, both parameters were markedly reduced by the H-1 antihistamine terfenadine in full and half-dosage. A combination of the two drugs both in "standard" and modified dosage resulted in the greatest reduction in the wheal and flare. Histamine and suxamethonium-induced wheals reacted in a similar manner to the antihistamines.
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A radioimmunoassay was devised for the human complement cleavage product, C3a, using charcoal separation and selective precipitation of interfering substances. When compared with the commercially available immunoassay now marketed, the assay reported here was somewhat simpler to perform; furthermore, it overcame delivery and availability problems in Europe. The assay showed a mean recovery of 87% of known amounts of C3a or C3adesarginine and had a sensitivity of 32 ng C3a per milliliter of plasma; coefficients of variance were comparable to other radioimmunoassays in common use. Using this assay in a first clinical application, we were able to document a small but statistically significant rise in [C3a] during cardiopulmonary bypass.
Thirty-nine melanocytic nevi of varying histologic structure and stages of development were examined for the presence of S-100 protein and melanoma-associated antigens (MAA) by the indirect immunoperoxidase technique, using a polyclonal anti-serum to S-100 protein and monoclonal antibodies to MAA. S-100 protein and MAA were found in the cells of all types of nevi, including dysplastic and congenital nevi. While S-100 protein was present in nevus cells at the epidermodermal junction and at all levels of the dermis, the melanoma-directed monoclonal antibodies BM 24-2, NKI/C-3, Mel-1, and Mel-2 reacted most prominently with the superficial (A-type) nevus cells; the B- and C-type cells being negative in these cells. An exception to this rule was melanoma-monoclonal antibody 34.1 which reacted with nevus cells at all levels; deep C-cells often being more intensely stained than the subepidermal A-cells. The cells of the different nevus cell layers, known to differ morphologically and enzymatically, are, thus, also different in their expression of MAA. Our data suggest that for most antibodies these variations may be due to differences in the metabolic activities of nevus cells at various distances from the epidermis.
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Despite the suggestion than an intolerance reaction could be a possible cause of chronic urticaria in some cases, the pathogenesis of this disease remains enigmatic. It is unlikely that an intolerance reaction to substances used in provocation testing is the cause of the daily rashes. It rather seems that the intolerance reaction is an indication of a certain instability of the mast cell membrane of other factors of the reaction cascade leading to the wheals. Fortunately, an effective symptomatic therapy is available in such cases where the cause cannot be detected and the trigger cannot be avoided. The modern, non-sedating H1-antihistamines have been tested in clinical-experimental studies as well as in a multicentric study in patients with chronic urticaria. In histamine-induced wheals, terfenadine was slightly superior to other non-sedating H1-blockers, when the grade of reduction of wheals and flare areas was taken as criterion. In clinical studies, another antihistamine, loratadine, was slightly, but statistically not significantly superior to terfenadine. In cases that cannot be effectively treated with H1-blockers alone, the additional administration of non-steroidal antiphlogistics (acetylsalicylic acid, indomethacin) is recommended. To avoid aggravation of the symptoms caused by the antiphlogistics, the drugs must be given in increasing dosages and after concurrent treatment with H1-blockers. With this combined therapy, about 50% of the patients present amelioration.