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Biomedical subjects

J H Olafsson

Publications and source records attributed to J H Olafsson.

28 records · Page 2Linked to original sources

Treatment of two mastocytosis patients with a histidine decarboxylase inhibitor.

Alpha-fluoromethylhistidine, alpha-FMH (L-641.575, Merck, Sharp and Dohme), a specific irreversible inhibitor of the mammalian histidine decarboxylase, was investigated for its effect on possible histamine symptoms in mastocytosis. Two patients were treated for 28 and 22 weeks respectively. The first patient had systemic mastocytosis and a severe malabsorption causing weight loss, excessive fecal fat losses and electrolyte disturbances, the main symptom being frequent diarrhoea. The second patient had mainly skin manifestations diagnosed as urticaria pigmentosa and the main symptom was pruritus. There were no side effects of the drug. The first patient produced formed stools after one week of treatment, concomitant with a decrease in plasma histamine and in urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid (MeImAA). In the second patient definite benefit of the treatment was observed after two months. However, changes in histamine parameters occurred earlier. Plasma histamine and urinary MeImAA were reduced after one week and in two or three weeks reached a steady-state level of about 25% of pretreatment values. The results indicate an effective inhibition of histamine synthesis in both patients but only the diarrhoea seemed to be causally related to the change in histamine metabolism.

Aged↗

Suppression of T lymphocyte mitogen response in patients with mastocytosis.

Immunological functions were studied in 22 patients with mastocytosis. Lymphocyte stimulation with concanavalin A (Con A) and phytohemagglutinin showed that the patients responded with lower mitogenic activity than healthy controls. Furthermore, the lymphocytes of patients with the most extensive mast cell disease had a significantly lower Con A mitogen response than the lymphocytes of the rest of the patients. The effect of histamine and its specific metabolites, tele-methylhistamine and tele-methylimidazoleacetic acid (MeImAA), on the Con A lymphocyte mitogen response was also studied in healthy controls. Histamine had a clear suppressive effect, while the metabolite tele-methylhistamine caused only slight inhibition and MeImAA apparently had no effect. The total T cell, suppressor and helper cell numbers, measured with monoclonal antibodies, and the amount of immunoglobulins in serum were found to be normal.

Adult↗

HLA and lymphocyte histamine sensitivity in mastocytosis.

HLA-ABC and DR typing was performed on 50 patients with mastocytosis. Lymphocyte stimulation with concanavalin A has earlier been performed in 22 of these patients. No phenotypic aberrations were detected in the patient group. 8 patients had the HLA-B12 phenotype. Lymphocytes from the HLA-B12 phenotype stimulated with a lymphocyte mitogen have earlier been shown to react with decreased inhibitory effect to histamine. 2 patients in this study had the HLA-B12 phenotype and systemic mastocytosis with high histamine turnover, but these patients reacted with a low mitogen response of the lymphocytes.

Adult↗

Cutaneous and systemic mastocytosis in adults. A clinical, histopathological and immunological evaluation in relation to histamine metabolism.

At the Department of Dermatology, Sahlgrenska sjukhuset, Göteborg, 58 patients with mastocytosis were investigated during the years 1979-1984. The purpose of this study was to examine the extent of the disease, the degree of mast cell infiltration in skin and bone marrow, to evaluate the most frequently used diagnostic methods, to study some immunological functions and genetic markers, to determine the histamine metabolism and to test a new drug which inhibits histidine decarboxylation. Besides a clinical examination, skin biopsies were taken from involved and uninvolved skin. The biopsies were fixed in 4% neutral formaldehyde or in an iso-osmotic mixture of 0.6% formaldehyde and 0.5% acetic acid (IFAA) and stained with toluidine blue 30 minutes or 5 days. The mast cell density in the formaldehyde fixed biopsies stained 5 days was significantly higher than the routine short stained biopsies. The same results were obtained with IFAA fixation and short toluidine stain. This might be caused by aldehyde blocking of dye-binding groups, which has been observed earlier in mucosal mast cells. Sternal aspirate and crista iliaca biopsies were done in order to examine the bone marrow. When comparing these two methods, the bone-marrow biopsy was found to be more reliable and sensitive when judging the mast cell increase. This resulted in more systemic mastocytosis patients being detected through crista biopsy than through sternal aspirate. Lesions with mast cells, eosinophils and lymphocytes were seen in the biopsies. These lesions may be an early sign of a systemic involvement of the disease. The urinary tele-methylimidazoleacetic acid (MeImAA) excretion was increased in most of the patients, and was found to correlate with the extent of the disease, both concerning organs involved and the mast cell numbers in the bone marrow. A lymphocyte stimulation with Concanavalin-A (Con-A) and phytohaemagglutinin (PHA) showed a decreased mitogenic response, especially in the patients with the highest histamine turnover. Inhibition was also seen when histamine was added to mitogen stimulated lymphocytes from healthy controls, while only a minimal inhibition of the mitogen response was obtained by histamine metabolites. Even if histamine in vitro seems to affect the lymphocyte mitogenic response, and the lymphocyte stimulation in the patients was inhibited, this does not seem to have any obvious clinical relevance. HLA-typing was carried out on 50 patients but no phenotypic aberrations were detected. Lymphocytes from patients with HLA-B12 seemed to react with the same mitogenic inhibition as those from other patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Studies on histamine metabolism in mastocytosis.

The urinary excretion of histamine and its main metabolite, 1-methyl-4-imidazoleacetic acid (MeImAA), was determined in 30 adult patients with the clinical diagnosis of urticaria pigmentosa (UP). Clinical and laboratory investigations including skin histology, bone marrow examination, and scintigraphy of the skeleton, liver, and spleen revealed systemic manifestations in 14 cases. Among the 16 cases with dermal proliferation of mast cells only 3 cases classified as telangiectasia macularis eruptiva perstans (TMEP). All patients with systemic mastocytosis and UP excreted increased amounts of MeImAA in the urine while normal amounts were found in 2 of the patients with TMEP. A significant correlation existed between MeImAA excretion and the extent of mast cell infiltration in skin and internal organs. No such correlation was found for urinary histamine. Urinary MeImAA but not histamine is therefore considered a useful indicator of systemic involvement by reflecting the size of the mast cell histamine pool. The main symptom of the patients was pruritus, which was moderate to severe in 17 and mild or absent in 13 cases. Gastrointestinal symptoms were present in 14 patients. However, there was no obvious correlation between the excretion of MeImAA and any of the symptoms recorded. Neither was the severity of pruritus correlated to the histamine content of the skin, which was measured in both lesional and unaffected skin in 23 of the patients. Thus, symptoms possibly caused by histamine in mastocytosis patients are not directly related to urinary histamine metabolite excretion or tissue histamine content.

Adult↗

Effect of antihistamins (H1 and H2), cortisone and beta-adrenergic stimulator on murine contact sensitivity and histamine metabolism.

A study on the influence of histamine receptor blockade, beta-adrenergic stimulation and cortisone on murine cutaneous inflammation and histamine metabolism has been performed. Cortisone was found to reduce the inflammation and urinary histamine excretion while histamine receptor blockade and beta-adrenergic stimulation did not influence the reaction. A good correlation existed between inflammation and urinary histamine excretion in all experiments. Contact sensitivity in the mouse was not found to be transferable with serum indicating that humoral antibodies play no essential role in this reaction in the mouse. On the basis of these results it is suggested that basophils might participate in murine contact sensitivity.

Adrenergic beta-Agonists↗

Inhibitory effect of transplanted syngeneic thymus fragments, thymus epithelium and thymocytes on the increased contact sensitivity reaction in the adult thymectomized mouse.

Thymectomy in the adult mouse leads to an increased ability to develop contact sensitivity. The effect of different types of thymus grafts to adult thymectomized mice on contact sensitivity was studied in the present investigation. An inhibition was observed after transplantation either of uncultured thymus tissue, cultured thymus epithelium or of thymocytes. The results of the study favor the hypothesis that a continuous production of suppressor cells regulates contact sensitivity in the adult mouse.

Aging↗

Single dose azithromycin treatment of gonorrhea and infections caused by C. trachomatis and U. urealyticum in men.

BACKGROUND AND OBJECTIVES: Single dose regimens have advantages in the treatment of STD. Azithromycin has unique pharmacokinetics that may make single dose regimens feasible. Treatment with a single 1 g dose of azithromycin was compared to 100 mg doxycycline twice daily for seven days. STUDY DESIGN: This was a randomized third-party blinded study on 183 male patients, 176 of whom could be evaluated for efficacy. RESULTS: Chlamydia trachomatis was cultured from 148 patients, 79 receiving azithromycin and 69 receiving doxycycline. Six patients receiving azithromycin had positive cultures on follow-up, four were known to have had sexual intercourse with infected partners. Fifty-one patients had gonorrhea; 28 were treated with azithromycin and 23 with doxycycline. Neisseria gonorrhoeae was eradicated from all patients except one receiving azithromycin. He denied sexual exposure during follow-up. Sixty patients were infected with Ureaplasma urealyticum, 35 were treated with azithromycin and 25 with doxycycline. Five patients in each group had positive cultures on follow up. Three patients receiving azithromycin and two receiving doxycycline were known to have had sexual exposure during follow-up. CONCLUSION: A single dose of azithromycin showed similar effectiveness as a 7-day regimen of doxycycline.

Adolescent↗