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Biomedical subjects

A Nyfors

Publications and source records attributed to A Nyfors.

At least 55 records · Page 3Linked to original sources

Cytogenetic effects of methotrexate on human cells in vivo: comparison between results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test.

Cytogenetic studies were performed in 22 patients treated with methotrexate (MTX). In some patients, metaphases from both bone-marrow cells and peripheral blood cells were studied. In the bone-marrow preparations an increased number of structural chromosomal aberrations was present, whereas abnormalities were not observed in the peripheral blood cells. An examination of the bone-marrow chromosomes must therefore be included in the study of the possible chromosome-breaking effect of chemical agents. The results obtained with the micronucleus test and chromosome studies were compared in 10 patients treated with MTX. The micronucleus test was more sensitive than the chromosome analysis as regards the clastogenic effect of MTX.

Bone Marrow↗

Decrease in neutrophils observed in vivo in psoriatics after PUVA therapy.

In 56 patients leucocyte and differential counts were done before and at weekly intervals during PUVA treatment of chronic recalcitrant psoriasis. A statistical significant (P less than 0.01) decrease in the percentage of neutrophils was observed during the first week of the PUVA therapy. This observation could be closely related to the clinical clearing of psoriasis (P = 0.02). The effect of PUVA therapy in psoriasis may be due to a decrease in the number of immunocompetent neutrophils demonstrated in psoriatic lesions.

Female↗

Morphogenesis of fibrosis and cirrhosis in methotrexate-treated patients with psoriasis.

Serial liver biopsies before and after Methotrexate therapy were performed in each of eight patients with severe, recalcitrant psoriasis treated for years with Methotrexate in a single, weekly, oral dose not exceeding 25 mg per dose. A total of 31 liver biopsies was studied. The study revealed liver damage commencing with small foci of piecemeal necrosis, followed by the destruction of the limiting plate and the occurrence of stellate periportal fibrosis. Eventually, partial and then whole fibrous septa developed between portal tracts and between portal tracts and central veins, with resultant distortions of the lobular architecture. In two patients with an admitted daily alcoholic intake, additional findings were seen, including alcoholic hepatitis, centrilobular fibrosis and development of partial and whole fibrous septa between the central vein area, and portal tracts adding to the number of septa running between the portal tracts and central veins which split up the lobules. The following conclusions seem probable: 1) Methotrexate therapy in psoriatics may cause development of fibrosis or cirrhosis; 2) the morphological changes during this development follow a consistent pattern; and 3) the pathogenesis of the development of fibrosis and cirrhosis is mixed in some cases, being dependent on both alcoholic and Methotrexate intake.

Adult↗

Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics.

The purpose of this paper is to report findings in post-MTX liver biopsies from 160 psoriatics treated with Methotrexate (MTX) in single biopsy and B. 68 patients with serial biopsies. At the time of liver biopsy the 92 patients had received a mehosis and six patients had fibrosis. Comparing these 7 patients with patients having normal liver histology (13 patients) revealed no statistically significant difference in cumulative doses of MTX, but a statistically significant higher admitted alcohol intake during MTX therapy (p less than 0.002) and an older age (p less than 0.01) in the patients with cirrhosis or fibrosis. in the 68 patients MTX had accumulated to a mean dose of 3940 mg (range 32k-8355 mg) at the time the latest liver biopsies were taken. Among the latest liver biopsies were 14 cirrhosis (21 per cent, 95 per cent confidence limits: 12-32 per cent) and 16 fibrosis (24 per cent, 95 per cent confidence limits: 14-35 per cent). The 14 patients with cirrhosis when compared to patients with normal histology (9 patients), had taken an equal total dose of MTX at the latest liver biopsy, but had consumed a statistically significant higher amount of alcohol (p less than 0.05) during MTX therapy and also tended to be older (p less than 0.006). Comparison of a material A and B indicates that the prevalence of cirrhosis and fibrosis among MTX treated psoriatics increases rapidly beyond a cumultative dose of two to four grams of MTX. No MTX treated psoriatics should thus be allowed to pass this dosage range without having a liver biopsy performed.

Adult↗

Studies of human semen in topical corticosteroid-treated and in methotrexate-treated psoriatics.

Ejaculates were studied from ten men with severa psoriasis treated with topical corticosteroids and from ten similar patients who had received methotrexate therapy from 1 to 9 years. It was not possible to demonstrate any unfavorable effect on the semen quality during the methotrexate therapy. The semen analysis was more frequently found normal (p = 0.04) in the methotrexate treated group, and no specific abnormality was found in spermatozoa of methotrexate-treated patients. Methotrexate therapy to male psoriatics seems safe and in agreement with this no congenital abnormalities have been reported. A remarkable number of the ejaculates had reduced sperm qualities, and it is proposed that this might be due to psoriatic lesions in the genital tract.

Administration, Topical↗

Liver ultrastructure in psoriatics related to methotrexate therapy. 1. A prospective study of findings in hepatocytes from 24 patients before and after methotrexate treatment.

To show what damage occurs in the hepatocytes of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 24 psoriatics with severe psoriasis before and after MTX therapy were studied blind by light and electron microscopy. We also aimed to determine the severity of lesions and find possible correlations, and to seek a relationship of these observations with light microscopical and clinical findings. The present study has shown that MTX probably caused damage to the hepatocytes reflected in the membrane whorls (p less than 0.05) and the accumulation of lipid droplets (p less than 0.05). There was an increase (p less than 0.05) in autophagic vacuoles, which mostly contained glycogen and cell sap with residual bodies. These residual bodies were then found in an increased number in the nearby Kupffer cells. Crystals were found in megamitochondria in most patients before and after MTX therapy. Some of these crystals were found free in the cytoplasm. Mitochondria containing crystals were shown in autophagic vacoules, representing possible pathways of their breakdown. Bile canaliculi commonly contained debris but only one patient had evidence of cholestasis. There was no significant change in nuclei, Golgi apparatus, or the endoplasmic reticulum and no statistically significant correlation between the shown changes and the total dose of MTX given.

Cell Membrane↗

Liver ultrastructure in psoriatics related to methotrexate therapy. 2. Findings in bile ducts from 11 methotrexate treated psoriatics and 2 controls.

To determinate what damage occurred in the bile ducts of psoriatics receiving Methotrexate (MTX) therapy liver biopsies from 11 patients were studied with the light and electron microscope and compared with normal material. Thick sections (1 micrometer) showed light and dark cells in biliary epithelium and lipofuscin granules. At the ultrastructural level these were confirmed. The lumen of the bile ducts contained debris. The microvilli were decreased in number and damaged forms appeared. Damage to the biliary epithelial mitochondria was widespread and there were foci of intracellular oedema. The Golgi apparatus was hypertrophied and dilated. Atrophic cells were seen. The lateral intercellular spaces were dilated and contained debris and the basement membrane showed zones of duplication. Similar changes were found in the ducts of Hering.

Adult↗

Improvement of recalcitrant psoriasis vulgaris after tonsillectomy.

To study the effect of tonsillectomy as a possible part of the treatment of infection-released, relapsing and recalcitrant (to topical therapy and courses of penicillin) psoriasis vulgaris in children and adolescents and to test a possible correlation between tonsillitis and exacerbations of psoriasis vulgaris, a retrospective study (charts and questionnaires) of the course of psoriasis after tonsillectomy was undertaken in 74 patients with such psoriasis. Each patient served as his own control. At tonsillectomy the average age of patients and the duration of psoriasis were 14-2 years and 4-5 years, respectively, while the average follow-up period was 4-5 years. The clearing of psoriasis vulgaris was stastically significant, p less than 0-01, as 1/3 of the patients obtained clearing of psoriasis throughout the entire follow-up period, while an additional 1/3 noticed considerable improvement of their psoriasis. After having tried both topical therapy of various sorts and courses of penicillin, tonsillectomy might be taken into consideration in relapsing, recalcitrant psoriasis vulgaris in children and adolescents.

Adolescent↗

Liver biopsies from psoriatics related to methotrexate therapy. 1. Findings in 123 consecutive non-methotrexate treated patients.

A prospective study was started in 1969 to describe morphological features of liver biopsies from patients with severe psoriasis. Among 123 patients evaluated for possible MTX therapy, liver biopsies disclosed pathological histology (maninly fatty change and/or non-specific reactive hepatitis) in 51 per cent. The incidence of pathological liver histology did not statistically correlate with psoriasis parameters such as duration and extent. However, statistically significant correlations (p less than 0.0001) were found between the frequency of pathological liver histology and other factors such as age, obesity, and daily alcholic intake. Comparison of liver histology with SGOT value at the time of liver biopsy showed that while the diagnostic specificy of this test high (1.00), the diagnostic was low (0.17). Normal values of SGOT should not be relied upon to indicate all types of liver pathology. A "risk index" indicating the probability of pathological liver histology was developed. It is calculated as follows: two times the height (cm) minus weight (kg) minus age (years) minus 50 (in case of daily alcoholic intake) minus 50 (in case of elevated SGOT). To elucidate liver histology and particularly to rule out fibrosis and cirrhosis, a liver biopsy should be performed in every psoriatic patient with a low score in the risk index prior to beginning MTX therapy.

Adult↗

Effect of methotrexate therapy in psoriatics on the Ito cells in liver biopsies, assessed by point-counting.

To evaluate the relationship, both quantitative and qualitative, between the Ito cells and methotrexate (MTX) therapy Ito cells were studied by light microscopy in 1 mum toluidine blue stained sections and by electron microscopy in 24 pairs of Menghini needle biopsies before and after MTX therapy of 24 consenting patients with severe psoriasis. Light microscopy showed a statistically significant increase in pathological findings (P less than 0-05) and in the number of Ito cells and their size (P less than 0-0001) after MTX therapy. It was not possible to show a statistically significant correlation between the increase in the number of Ito cells and the cumulative dose of MTX. Ultrastructural analysis of Ito cells showed no marked difference from pre to post-MTX specimens. The fibrosis and cirrhosis seen after MTX therapy in some liver biopsies from psoriatics and the post-MTX increase in the number of Ito cells direct attention to the possible role of Ito cells as fibroblast precursors.

Adult↗

Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study.

Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology.

Adult↗

The relation of HL-A antigens to liver histology in methotrexate-treated psoriatics.

A total of 45 patients with severe psoriasis vulgaris treated with Methylaminopterin NFN (Methotrexate Lederle) were HL-A typed in order to seek a possible correlation between HL-A antigens and the histological abnormalities in post-Methotrexate (MTX) liver biopsies. Highly significantly increased frequencies of w17 and TY (P less than 0.0001) were found, while HL-A13 Was only slightly increased. No statistically significant correlations were found between HL-A antigens and liver histology. HL-A typing does not seem to be of any predictive value in the pre-MTX screening of psoriatics in order to rule out patients with a high risk of liver damage during long-term MTX therapy.

Adult↗

Improvement of refractory psoriasis vulgaris after tonsillectomy.

In order to ascertain what effect tonsillectomy may have in the treatment of children and adolescents with recurring psoriasis vulgaris, refractory to topical therapy and courses of penicillin, and triggered by infection, and also to test a possible correlation between tonsillitis and exacerbations of psoriasis, a retrospective study of the course of psoriasis after tonsillectomy, using charts and questionnaires, was undertaken in 74 psoriatic patients. Each patient served as his won control. The average age of the patients at tonsillectomy and the duration of psoriasis were 14.2 years and 4.5 years, respectively, while the average follow-up period was 4.5 years. The clearing of the psoriasis was statistically significant (p less than 0.01) as it occurred throughout the entire follow-up period in one-third of the patients, while an additional third noticed considerable improvement of their psoriasis. After trying tropical therapies of various sorts as well as courses of penicillin, tonsillectomy might be considered for recurring, refractory psoriasis vulgaris in children and adolescents.

Adolescent↗