Biomedical subjects
Publications and source records attributed to L Molin.
A method for evaluation of radioimmunoassay results is described. The order of the single tubes in each assay run is randomized. A polynomial is fitted to untransformed data (y = counts per minute; x = concentration of curve.A confidence interval is calculated for each sample, taking into account the variance of the standard curve and that of the actual duplicate assay jointly.
The Scandinavian Mycosis Fungoides Study Group includes dermatologic clinics in Denmark, Norway, and Sweden. The results of the first three years of activity are presented herein. In plaque stage, topical nitrogen mustard was highly effective. Preceding intravenous tolerance induction seems to be of no value. PUVA induced equally high remission rates. Both modalities were also highly effective in cutaneous tumor stage. In advanced tumor stage and in case of extracutaneous involvement systemic chemotherapy was given. Topical treatment alone was more effective on the cutaneous lesions including tumors than systemic chemotherapy alone. Therefore a combination of topical and systemic treatment is recommended in advanced stages of mycosis fungoides.
Combination chemotherapy with cyclophosphamide, vincristine, VP-16, adriamycin and prednisolone was given in 9 cases of mycosis fungoides in the tumor stage; 3 of these patients received COP, one received CHOP, and 5 CAVOP. Complete remission was obtained in one case and partial remission in 5, the response rate thus being 6/9. It was impossible, however, to maintain remission. The treatment was reduced or withdrawn owing to toxic effects in 4 cases. These forms of combination chemotherapy are beneficial in non-Hodgkin lymphomas but do not seem to be of value in the tumour stage of mycosis fungoides.
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The influence of different contraceptive techniques on the incidence of pelvic inflammatory disease (PID) in 672 patients with gonorrhoea have been studied. The lowest frequency of PID was found in patients using hormonal contraceptives (Group A), 8.8 per cent compared to 23.5 per cent in patients using intrauterine devices (Group B) and 15.1 per cent in patients using neither technique (Group C). In comparable control groups no significant differences in background factors, such as age, marital status and sexual activity were demonstrated. It is therefore concluded that the significantly lower incidence of PID in patients using hormonal contraceptives compared to the other groups and the high incidence of PID in patients using intrauterine devices is related to the contraceptive technique per se.
Sulfasalazine and its active components, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), are potent modulators of inflammatory reactions but with somewhat different modes of action. Investigating the effect of these compounds on normal human polymorphonuclear leukocytes in vitro, we show inhibition of different stages in the phagocytic process, such as migration (sulfasalazine and SP), superoxide production (sulfasalazine and SP), myeloperoxidase-mediated iodination and cytotoxicity (5-ASA and SP). It is thus suggested that sulfasalazine is not just a vehicle for delivering its active components in the colon, but that its therapeutic effect is ulcerative colitis and other inflammatory reactions is a result of the concurrent action of the three compounds.
Samples from two pools were sent 10 times to 27 laboratories for assay of digoxin. One pool contained digoxin 2.60 nmol/l in normal plasma (SP); the other was pooled plasma from patients treated with digoxin (PP). Ten radioimmunoassay (RIA) methods were used. The mean of SP assays was 2.59 nmol/l, not significantly different from 2.60 nmol/l. The mean of PP determinations was 2.46 nmol/l. Within each of the 10 assay rounds, the concentrations showed an almost twofold variation and S.D. averaged 0.33 nmol/l and 0.31 nmol/l for SP and PP respectively. Significant differences (P less than 0.001) were found between mean concentrations obtained for the pools at various laboratories (SP range 2.15-2.85 nmol/l; PP range 2.12-2.72 nmol/l). The laboratory means obtained for SP and PP correlated significantly (P less than 0.001). Nevertheless, significant (P less than 0.01) variations between laboratories were found also concerning the mean difference between SP and PP concentrations. The interassay SD of the assays differed significantly between laboratories (range 0.05-0.61 nmol/l. Between and within groups of laboratories using the same RIA method and between various types of laboratories, differences were also found concerning both accuracy and precision of the assays. It is concluded that a better control of digoxin assay is needed.
We evaluated four commercial radioimmunoassay kits for digoxin. We assayed a standard plasma containing digoxin, 2.0 microgram/L, and samples from patients receiving digoxin, with use of the kits and of a bioassay, the 86Rb-uptake inhibition technique. Intra-assay precisions differed significantly. Computer-calculated 95% confidence intervals for the radioimmunoassays averaged 0.4 to 0.6 microgram/L at the proposed toxic threshold of 2.0 microgram/L; the corresponding value of the 86Rb assay was 0.75 microgram/L. Digoxin in the standard plasma was overestimated with three of the kits (means: 2.40, 2.56, and 2.59 microgram/L) but was assayed accurately by the 86Rb technique and by one kit. This same kit gave a significantly lower mean (1.07 microgram/L) for the patients' samples then did the other three kits (1.32, 1.49, and 1.29 microgram/L), two of which also differed significantly in accuracy. The 86Rb assay measured glycoside activity corresponding to a mean digoxin concentration of 1.35 microgram/L. We conclude that the relatively low precision of digoxin assay and the variations in accuracy between kits from various vendors apparently deserve continual attention.
The Scandinavian Mycosis Fungoides Study Group have treated 19 patients with mycosis fungoides in tumour stage by systemic chemotherapy. Nine patients were treated with Bleomycin 15 mg i.m. twice weekly for 7 weeks and 10 patients with the same dose of Bleomycin in combination with Methotrexate 15 mg i.m. per m2 body surface each week for 7 weeks. No maintenance treatment was given. The immediate therapeutic effect of Bleomycin alone was considered good in half of the patients. Bleomycin and Methotrexate together produced a better initial effect. In both treatment series the remission was short-lived in the absence of maintenance therapy. The mortality rate was high, especially in combination treatment. Lethal complications occurred in 6 patients during the treatment, 3 of which were thromboembolic, one pancytopenia, one lung fibrosis with pulmonary insufficiency, and one bronchopneumonia. The conclusion is that these two forms of therapy cannot be recommended.
The Scandinavian Mycosis Fungoides Study Group has treated 21 patients with mycosis fungoides in plaque stages with topical, whole-body application of nitrogen mustard, 20 mg in 40 ml water per square metre. Ten patients were treated after previous attempts at intravenous tolerance induction ad modum van Scott & Kalmanson and eleven without. Complete remission was initially achieved in 10 patients and partial remission in 9 patients. Contact dermatitis to nitrogen mustard developed in 2/10 after tolerance induction and in 1/11 without tolerance induction. It is concluded that topical, whole-body application of nitrogen mustard gives high remission rates. In this series, however, many relapses occurred, due to inadequacy of the maintenance treatment. Tolerance induction has not been found of any value.
Epipodophyllotoxin (VP-16-213) was administered to 9 patients with mycosis fungoides in various stages, most of them in the advanced tumour stage. In 4 of the patients VP-16 was combined with cyclophosphamide. VP-16 alone or in combination with cyclophosphamide was capable of inducing remission initially in all cases, complete in 2, partial in 3 and improvement to a lesser degree in the remaining 5 patients, but it was unable to maintain the remission. The induced remission has to be upheld by other agents, possibly added to VP-16.
Prednimustine, a chlorambucil ester of prednisolone, was administered orally to 5 patients with mycosis fungoides in advanced tumour stage. Partial remission was obtained in 2 of the patients. However, we do not consider the agent to be particularly advantageous for the treatment of mycosis fungoides.
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The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.
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The acetylator phenotype of 35 healthy, drug-free volunteers and 21 patients with cardiac and/or renal disease has been assessed using oral sulphapyridine. Comparative evaluation of a simplified and a more selective method of sulphapyridine analysis was performed. Thirteen of the patients were also phenotyped by determination of plasma isoniazid half-life. 81% of the patients were slow acetylators, compared with only 51% of the volunteers. When phenotyping healthy, drug-free subjects the analytical procedure, involving a direct estimation of sulphapyridine in urine with the Bratton-Marshall procedure, was satisfactory. On the other hand, in patients receiving concomitant drug therapy the more selective analytical procedure was necessary in order to diminish the risk of methodological interference.
Fifteen patients with spontaneous systemic lupus erythematosus (SLE) have been phenotyped by determination of plasma isoniazid (INH) half-life. Seven patients had signs of renal insufficiency. Of the 15 patients, 13 were slow and only 2 rapid acetylators. No correlation was found between the plasma INH half-lives and the renal function. Thus, there is the same marked predominance of slow acetylators in patients with spontaneous SLE as in patients with the drug-induced SLE-like syndrome.