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Biomedical subjects

H Zachariae

Publications and source records attributed to H Zachariae.

At least 73 records · Page 4Linked to original sources

Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis.

Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis.

Alkaline Phosphatase↗

Serum aminoterminal propeptide of type III procollagen in systemic sclerosis. A follow-up--investigations in subclasses and during therapy.

Fifty-seven patients with systemic sclerosis were investigated for connective tissue turn-over related to type III collagen. Sera from 13 patients with diffuse cutaneous systemic sclerosis and 44 patients with limited cutaneous systemic sclerosis were analysed for aminoterminal propeptide of type III procollagen (PIIINP) by a radioimmunoassay based on human propeptide. Increased levels of PIIINP in serum correlated with skin involvement and the clinical course. All patients with diffuse cutaneous systemic sclerosis had levels above the normal range, and in limited cutaneous systemic sclerosis elevated PIIINP levels seemed to be correlated with rapid progression and with extension of lesions. Immunosuppressive drugs, cyclosporin A, and prednisone with or without cyclophosphamide, which were given to patients with rapid disease progression, significantly reduced PIIINP. This was also the case with penicillamine, but to a lesser degree. Our data support the suggestion that immunosuppressive agents are justified in rapidly progressive, life-threatening or disabling disease, when used with the necessary precautions. Serum PIIINP may be utilized as a marker of type III collagen fibrogenesis in systemic sclerosis and be of prognostic value. PIIINP may also be of use in the differential diagnosis between diffuse cutaneous systemic sclerosis and scleredema.

Drug Therapy, Combination↗

[Mycosis fungoides. A review of the clinical picture, treatment and course in 107 patients].

During the period 1972 till the end of 1987, 107 patients with the diagnosis of mycosis fungoides or cutaneous T-cell lymphoma were examined and treated in the Department of Dermatology, Marselisborg Hospital. This disease belongs to the group of non-Hodgkin T-cell lymphomata. The diagnosis is based on the occurrence of red, scaly plaques in the skin associated with itching or tumours in the skin and, simultaneously, of a pleomorphic infiltrate consisting of CD4-positive T-lymphocytes which show characteristically exocytoses in the epidermis with subsequent formation of Pautrier's microabscesses. The disease may progress with spread to the regional lymph nodes where lymphomata develop. Treatment is initially local with employment of chlormethin ("nitrogen mustard gas") and this treatment can maintain the patients in remission for prolonged periods. In cases with spread to lymph glands or in particularly aggressive forms with tumour formation in the skin, combined chemotherapy is administered (prednisone, cyclophosphamide, etretinate and bleomycin). Thirty-eight of the patients were in stage I in which a clinical suspicion of mycosis fungoides was present but where the histological changes were insufficient to confirm the diagnosis. IVa and ten in stage IVb. The age at the onset of the symptoms was from 59 to 64 years (median values) for the various stages. Stages I and II had approximately 80% five-year survival, while the stages with more extensive spread had approximately 50% survival. The etiology of the disease is unknown but, during recent years, certain evidence has been found suggesting that activation of a retrovirus in the epidermis may be a contributory factor.

Antineoplastic Combined Chemotherapy Protocols↗

Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma.

Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone. Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission. Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects. Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly. Etretinate (0.7 mg/kg) was given orally. The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Methotrexate side-effects.

Methotrexate is by far the most widely used cytotoxic drug in psoriasis. Treatment requires normal kidney, liver and bone-marrow function, and pregnancy and alcohol abuse are absolute contraindications. Serious toxic reactions are recognized, but can be avoided if the drug is used correctly. The most important side-effects are haematopoietic and hepatotoxic. It is well established that long-term methotrexate can induce liver damage which, in a number of patients, may lead to fibrosis or cirrhosis. Recent studies have, however, documented that the methotrexate-induced liver cirrhosis is not aggressive. Interaction can occur with a number of drugs; serious problems in particular may arise with concomitant use of sulphonamides and salicylates. The recommended guidelines for methotrexate use in psoriasis should be followed and patients given clear instructions.

Adult↗

Cyclosporin A treatment of systemic sclerosis.

Ten patients with severe progressive systemic sclerosis were treated with cyclosporin A at dosages of 1.5-7.5 mg/kg per day:two patients showed a marked improvement with softening of the involved skin; in one patient there was healing of persistent digital ulcers; one patient showed initial improvement followed by a marked exacerbation; one patient was slightly improved; two patients were unchanged. The clinical results correlated well with levels of serum aminoterminal propeptide of type III procollagen. In the eight patients completing treatment, side-effects such as slight tremor and a transient increase in the serum creatinine and blood pressure were either absent or reverted to normal when the dosage was decreased, except one case who had to be treated with anti-hypertensive drugs.

Adult↗

Kidney biopsies in methotrexate-treated psoriatics.

Kidney biopsies were studied in 19 psoriatics treated with methotrexate (MTX) from 1 month to 16 years. Only 3 of the patients had received the drug for less than 1 year. Four patients had been treated for more than 10 years. The total doses of MTX ranged from 30 to 14,340 mg. In 17 of the 19 patients the cumulative MTX dose was 500 mg or more. In 9 patients the cumulative doses were over 2 g. With the exception of 1 patient, which presented sequelae of acute renal failure unassociated with MTX treatment, all other biopsies showed renal structures which, assessed by routine judgement, were found normal. Semiquantitative evaluation of interstitial fibrosis and arteriolar hyalinosis as well as interstitial volume estimated by morphometry showed no significant changes. No patient showed clinical or laboratory signs of renal impairment.

Adult↗

Serum aminoterminal propeptide of type III procollagen in progressive systemic sclerosis and localized scleroderma.

Sera from 31 patients with progressive systemic sclerosis (PSS), 5 patients with widespread localized scleroderma (LS), and 3 patients with lichen sclerosus et atrophicus were analyzed for aminoterminal propeptide of type III procollagen (PIIINP) using a radioimmunoassay based on human propeptide. Thirty-eight per cent of the patients with PSS had levels above normal range, including all of the 3 patients with diffuse scleroderma. The same applies to 4 of 5 patients with widespread localized LS, while PIIINP in all 3 patients with lichen sclerosus et atrophicus were within normal levels. In patients with acrosclerosis, elevated PIIINP seems to be correlated to rapid progression and extension of lesions. A significant increase in PIIINP was found in a patient following discontinuation of prednisone and cyclophosphamide, while the present investigation did not allow judgement of effects of treatment with either penicillamine or cyclosporin A.

Humans↗

Serum aminoterminal propeptide of type III procollagen. A non-invasive test for liver fibrogenesis in methotrexate-treated psoriatics.

Serum aminoterminal propeptide of type III procollagen (PIIINP) was studied in 73 psoriatics receiving methotrexate and in 11 selected for trial with methotrexate or etretinate. 72 of the patients on methotrexate were also investigated with liver biopsies. The highest PIIINP value was found in a patient with ascites and her PIIINP decreased after medication was discontinued. Psoriatics with fibrosis or cirrhosis in their liver biopsies had a significantly higher mean PIIINP than patients without fibrosis, who had the same mean value as psoriatics prior to treatment. Based upon the individual data together with data from serial PIIINP investigations of 11 patients studied during treatment, it is concluded that PIIINP can be utilized as a valuable non-invasive test for liver fibrogenesis in methotrexate-treated psoriatics. PIIINP is not specific for the liver, but the study indicates that the number of liver biopsies can be reduced in psoriatics on methotrexate who have normal levels of PIIINP.

Biomarkers↗

The red man syndrome. Exfoliative dermatitis of unknown etiology: a description and follow-up of 38 patients.

Thirty-eight patients with erythroderma of unknown etiology were diagnosed over a 15-year period, and represented 19% of all patients admitted to our department for erythroderma. The male:female ratio was 6.6:1, and the median disease duration was 2 years (range 1 to 23 years). Keratoderma of palms and/or soles was seen in 79%. Laboratory findings were normal, except for an increased IgE level in 69% of the patients studied. Lymph node histology showed dermatopathic lymphadenopathy. Bone marrow investigation results were normal in 48%, or showed eosinophilia (32%) or hyperplasia (20%). Initial skin biopsies showed nonspecific histology in most patients, but later biopsies revealed pleomorphic infiltration. During the observation period four patients progressed to mycosis fungoides and another nine patients were suspected of having mycosis. None developed Sézary's syndrome. Only one third of the patients went into complete remission; half of them died during the observation period. Patients with erythroderma of unknown etiology are predominantly men and seem to belong to a certain subgroup--herein called the red man syndrome.

Adult↗