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L Molin

Publications and source records attributed to L Molin.

At least 55 records · Page 3Linked to original sources
PubMed1986

Factors of importance for valid digitalis assays particularly for the determination of digoxin in plasma and urine.

Four commercial radioimmunoassay (RIA) kits for digoxin varied in precision (coefficient of variation, CV within-assays 5-14%) and accuracy (up to 40%). Thus it seems that such commercial RIA-kits can reach at best a CV within-assay of 5% and a similar variation between assays. Without a good control of the performance, the variation can increase 5-6 times. We found that the precision of digoxin RIA as performed at 27 Swedish laboratories using 10 different methods varied from 0.05 to 0.61 nmol/L in between-assay SD for a pool of 2.60 nmol/L. Up to 100% deviations between the highest and lowest reported concentration of a spiked plasma pool may occasionally occur. Such deviations mostly depend on the laboratory, but there are contributions from the kit and effects of the matrix as well. Matrix effects were observed in plasma samples from patients with uremia, acute myocardial infarction and treated with spironolactone to which digoxin was added to a concentration of 2.50 nmol/L. We found 10% underestimation by one method, 10% overestimation by two methods and 5% overestimation by a fourth method, respectively, with the above described samples. For a good judgement of a found plasma concentration value, calculation of a confidence interval is useful. This can be done by computer fitting of the standard curve after duplicate runs of standards and samples in random order. One source of error in RIA appears to be the use of inaccurate standards. We found that standards provided with different RIA-kits for digoxin varied up to 30%. Various physicochemical properties of cardiac glycosides, which could influence the assays were studied. Both digitoxin and digoxin are sparsely soluble in water (5.1 and 36 mumol/L, respectively). Methanol is a much better solvent, which dissolves 6.9 mmol/L of digoxin and 20-24 mmol/L of digitoxin. Chloroform is a good solvent for digitoxin (29-34 mmol/L) but not for digoxin (0.42 mmol/L). Partition of cardenolides between chloroform and water reflected their lipophilic or hydrophilic character. Thus, digitoxin had a high affinity to the organic phase (distribution constant KD = 10(3.65)), while the hydrophilic deslanoside was preferentially found in the aqueous phase (KD = 10(-3.08). Interestingly, the sugar moiety digitoxose in the digoxin molecule turned out to be a substituent that increased lipophilicity. Adsorption of cardiac glycosides occurs to plastics and glass from aqueous solutions. To overcome losses at low concentrations, the solutions must contain plasma, albumin, alcohol or similar solubility-increasing ingredients.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1985

Some observations on various dose regimens of thymopentin treatment in rheumatoid arthritis.

Eight patients suffering from active rheumatoid arthritis were treated with thymopentin, 50 mg, administered as fractionated intravenous infusion over 10 min 3 times weekly for 3-20 weeks. Seven patients experienced clear-cut amelioration of symptoms and signs after just 2-4 weeks of treatment, and this improvement lasted for 6-8 weeks after thymopentin had been discontinued. Comparable positive results were observed in 2 patients who later continued thymopentin therapy by subcutaneous administration. Several subcutaneous dose regimens were tried; the optimal response appears to be achieved with 100-150 mg three times weekly and 150-200 mg twice a week, respectively. Because the subcutaneous therapeutic approach is more attractive to the patient-and also more practical for the physician-it should be investigated further.

Adjuvants, Immunologic↗
PubMed1985

Thymopentin treatment of herpes simplex infections. An open, monitored, multicenter study.

Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.

Adjuvants, Immunologic↗
PubMed1985

Thymopentin in chronic Trichophyton rubrum infection.

The case histories of 2 patients with chronic Trichophyton rubrum infections are presented. Both subjects had previously been treated systemically with griseofulvin, but had to be dropped from therapy due to adverse reactions. Topical treatment alone yielded unsatisfactory results. Thymopentin, 50 mg, administered subcutaneously three times weekly for a period of 6 weeks, induced rapid improvement within 3 weeks and almost complete remission 3 weeks later, although the fungi were still present on the skin. This beneficial effect lasted for up to 7 months after cessation of thymopentin therapy. Reinstitution of treatment produced the same response pattern. The clinical and immunological implications of these findings are briefly discussed; thymopentin is believed to enhance the suggested impaired cellular immunity in patients with chronic T. rubum infections.

Adjuvants, Immunologic↗
PubMed1984

Histamine release from mast cells during phagocytosis and interaction with activated neutrophils.

Histamine release from rat peritoneal mast cells was evaluated during interaction with IgG, C3b-bi and Concanavalin A-opsonized yeast particles and activated neutrophils. In contrast to others we could show no phagocytic uptake of yeast particles attaching to Fc, or Concanavalin A receptors on the mast cell. Attached yeast particles opsonized with C3b/bi were also poorly ingested (less than 10% of the attached particles.) Neither could we detect any significant histamine release. If, however, neutrophils were added to the mast cell-yeast particle complex, histamine release was induced particularly in the presence of Concanavalin A-yeast. We furthermore showed that phorbol myristate acetate-activated neutrophils and eosinophils initiated mast cell degranulation and histamine release. This release is not dependent on myeloperoxidase, but on other oxidative metabolites, since myeloperoxidase-deficient neutrophils also induce histamine release. These experiments show that mast cells exposed to immune complexes and activated neutrophils or eosinophils may augment the inflammatory response.

Eosinophils↗
PubMed1984

Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient.

Patients lacking the primary granulae enzyme, myeloperoxidase (MPO), do not usually show any increased susceptibility to infection or altered inflammatory response, in contrast to several other biochemical defects in polymorphonuclear neutrophils. We have now evaluated the role of MPO on phagocyte function in a patient with complete MPO deficiency suffering from generalized pustular psoriasis. We found that the MPO-deficient neutrophils showed enhanced phagocytosis (greater than 200% of normal) of IgG- and C3b-opsonized yeast particles and prolonged N-formylmethionyl-leucyl-phenylaline-mediated stimulation of superoxide production. When purified human MPO was added to normal neutrophils during cell adhesion, their Fc- and C3b-mediated phagocytosis was reduced without affecting cell viability. 1 microgram/ml of MPO reduced the Fc and C3b phagocytosis to 47 and 65%, respectively, whereas 10 micrograms/ml reduced the activity to 20 and 54%. Both attachment and ingestion were reduced to a similar extent, indicating that MPO affected the receptor function per se. When MPO was added to the hyperactive MPO-deficient cells, phagocytosis was reduced more rapidly. Catalase, azide, and methionine eliminated the inhibitory effect, and catalase and methionine, in fact, enhanced the phagocytic activity of adherent neutrophils. These data indicate that, apart from being a potent antimicrobial system, the oxidizing activity of the MPO-H2O2-halide system may modulate the inflammatory response by impairing certain receptor-mediated recognition mechanisms of phagocytic cells, which otherwise could elicit inflammatory reactions and tissue injury.

Complement C3b↗
PubMed1984

13-cis-retinoic acid effective in mycosis fungoides. A report from the Scandinavian Mycosis Fungoides Group.

Twenty patients with mycosis fungoides and four with Sézary's syndrome were treated with 13-cis-retinoic acid as single therapy in an initial dose of 1 to 2 mg per kg body weight in most cases. Complete remission in mycosis fungoides was obtained in six cases (33%) and partial remission in another ten cases (50%). No convincing response was observed in three cases, and progression of limited nodular lesions occurred in one case. In cases responding to treatment the first sign of remission was observed within two to four weeks. Our short-term experience is that the drug is effective in early as well as advanced stages of mycosis fungoides. Patients with Sézary's syndrome, however, did not respond to the same extent.

Adult↗
PubMed1984

The effect of thymopentin treatment on the relapse rate in frequently relapsing herpes simplex virus infections.

Twenty-four patients suffering from longstanding severe recurrent herpes simplex, who had not responded to prior therapy, were treated with s.c. thymopentin injections 50 mg, three times weekly, over a period of six weeks. They were followed up at weekly intervals over this period and then six weeks later. Moreover, the longest relapse-free period observed in the year after the treatment was recorded in the investigator's documentation. Thirteen of the 14 patients with labial herpes simplex and 10 of the 13 patients with genital herpes simplex improved markedly as shown by a decrease in the relapse rate of at least 50%, shorter episodes of relapse and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than four months after cessation of the therapy. No serious side-effects were observed. Laboratory examinations before, during and after thymopentin did not reveal significant alterations except for an increase in the T-helper/T-suppressor ratio. The effect of thymopentin is assumed to be due to T-helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon.

Adult↗
PubMed1984

First observations on high-dosed and long-term thymopentin treatment in active rheumatoid arthritis.

In this pilot study carried out in two centres, six male and two female patients with severe active rheumatoid arthritis (RA) (average duration over 10 years) were treated with thymopentin 50 mg in the form of prolonged i.v. injection (over 10 min), 3 times weekly for 3 to 20 weeks. Two of these patients were subsequently treated with different s.c. doses of thymopentin in a crossover fashion for more than two years, including periods without any treatment or treatment with placebo. The overall clinical efficacy was judged by assessing pain patterns and joint status and the functional stage of the patients according to Steinbrocker; in addition, the sedimentation rate was measured before and after the therapy. Seven out of eight patients showed definite improvement in their clinical status as assessed by the Steinbrocker scale. Most of the symptoms, particularly pain, capsular swelling, tenderness and morning stiffness, were remarkably reduced within 3 weeks of thymopentin treatment. Sedimentation rate decreased in five out of eight patients. Prolonged i.v. injections seemed to have somewhat better effects than s.c. administration; in the latter group the highest dose (3 X 100 mg/week or higher) produced the best results. During placebo treatment and during the medication-free intervals both groups of patients got worse. No side-effects occurred during the study.

Adult↗
PubMed1983

Reproducibility of standard preparation in digoxin radioimmunoassay in plasma and serum.

We studied the reproducibility of standard preparations in digoxin radioimmunoassay in a randomized trial using serum and plasma as matrices. The errors expressed relative to the observed counts per minute (cpm) attributable to each of the procedures involved in the preparation of standards were as follows: preparation of stock solutions and dilutions, 1.3%; addition of diluted solutions to the medium, 1.2%; and residual error due to the assay procedure, 3.7%. No error caused by mixing, portioning, and storage was detected. Heparinized plasma gave lower cpm values than serum at 4.0 ng/ml (p less than 0.01), an effect that would give over- or underestimations by about 5% at that level, depending on the medium used. This suggests that standard and sample matrices should be similar. Our procedure for preparing the standards seems to be reasonably reliable; this is necessary for satisfactory monitoring of patients on digitalis therapy.

Digoxin↗
PubMed1983

Granulocyte-mediated release of histamine from mast cells. Effect of myeloperoxidase and its inhibition by antiinflammatory sulfone compounds.

During phagocytosis, neutrophilic and eosinophilic granulocytes undergo metabolic activation and degranulation. This leads to accumulation of H2O2 and myeloperoxidase (MPO) or eosinophilic peroxidase (EPO) in the extracellular environment in inflammation. In the present investigation we show that the MPO-H2O2-halide system can degranulate isolated mast cells with release of histamine and 3H-serotonin. This is accomplished both in a system containing purified human MPO and in one containing phagocytosing neutrophils. When using purified MPO and a H2O2-generating system, the release was rapid, with 50% release after less than 20 min. The direct histamine release required less (0.65-2 micrograms/ml) MPO than did the release of 3H-serotonin (1-6 micrograms/ml). The release reaction was inhibited by azide, catalase but not superoxide dismutase. Studying the effect of the antiinflammatory sulfone compounds dapsone and sulfapyridine on the MPO-mediated histamine release, we show effective inhibition of the histamine release at concentrations of 0.025-0.2 mM of sulfone. 5-aminosalicylic acid exhibited some inhibition only in the cell-free system, whereas sulfasalazine was inactive. The antiinflammatory effect of dapsone in dermatitis herpetiformis and sulfasalazine in ulcerative colitis may in part be explained by their inhibitory effects on the granulocyte-mediated histamine release from mast cells in skin and mucosal tissue.

Anti-Inflammatory Agents↗
PubMed1982

[Sacroiliitis].

Explore the source record for details and available documents.

Arthritis↗
PubMed1982

Oral retinoid in combination with bleomycin, cyclophosphamide, prednisone and transfer factor in mycosis fungoides.

Oral retinoids seem to have been of great benefit in a non-randomized study on advanced mycosis fungoides using two different chemotherapy regimens, one with retinoid, the other without. Both groups also received a 3-drug chemotherapy with bleomycin, cyclophosphamide and prednisone. Complete remission including all signs of lymph-node involvement was found in 8 of 10 patients of the retinoid treated group, while none went into complete remission in the control group. All in the control group died between 3 and 12 months after therapy, whereas all but one in the retinoid treated group are alive. Other treatment differences between the groups were related to the use of transfer factor, topical treatment, and steroid administration. These differences make a final evaluation of the use of retinoids in mycosis fungoides difficult at the present stage. Further studies are needed.

Administration, Oral↗
PubMed1981

Determination of tritiated digoxin and metabolites in urine by liquid chromatography.

A liquid chromatographic method for the determination of digoxin, digoxigenin, its mono- and bisdigitoxoside and dihydrodigoxin in urine is described. Doses of 100 muCi of [12 alpha-3H]digoxin and 0.5 mg (640 nmol) of digoxin were administered orally to eight healthy volunteers. The compounds were extracted from urine with methylene chloride containing 3% of heptafluorobutanol. After separation, fractions corresponding to digoxin and the metabolites were measured by liquid scintillation counting. Conjugates of the glycoside metabolites were determined indirectly after pre-treatment of the samples with beta-glucuronidase-arylsulphatase. The detection limit was 0.1 nmol/l. Metabolites amounting to 0.5% of digoxin were assayed with a relative standard deviation of 5%. The advantages of the method are a high recovery in the extraction step, short separation times and the possibility of separate assay of dihydrodigoxin.

Chromatography, High Pressure Liquid↗