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Biomedical subjects

L Molin

Publications and source records attributed to L Molin.

At least 19 recordsLinked to original sources

Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients.

We studied metabolic, polypeptide and genetic variation in eight glutaric acidemia type II (GA II) patients with electron transfer flavoprotein (ETF) deficiency. As measured by 3H-fatty acid oxidations in fibroblasts, beta-oxidation pathway flux correlated well with clinical phenotypes. In six patients with severe neonatal onset GA II, oxidation of [9,10(n)-3H]-palmitate ranged from 2% to 22% of control and of [9,10(n)-3H]myristate, from 2% to 26% of control. Of two patients with late onset GA II, one had intermediate residual activities with these substrates and the other normal activities. Radiolabeling and immunoprecipitation studies revealed that three of the six neonatal onset GA II patients had greatly diminished or absent alpha- and beta-ETF subunits, consistent with a failure to assemble a stable heterodimer. Another neonatal onset patient showed normal synthesis of beta-ETF but decreased synthesis of alpha-ETF. Two neonatal onset and two late onset GA II patients showed normal synthesis of both subunits. Analysis of the pre-alpha-ETF coding sequence revealed seven different mutations in the six patients with neonatal onset GA II. The most common mutation was a methionine for threonine substitution at codon 266 found in four unrelated patients, while all the other mutations were seen in single patients. No mutations were detected in the two patients with late onset GA II.

Amino Acid Metabolism, Inborn Errors

PUVA and cancer: a large-scale epidemiological study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) therapy for treatment of skin disorders. A study of 4799 Swedish patients (2343 males, 2056 females; mean age at first treatment 45.3 years, range 6-93; mean follow-up 6.9 years males, 7.2 years females) who received PUVA between 1974 and 1985 showed a dose-dependent increase in the risk of squamous cell cancer of the skin. Male patients who had received more than 200 treatments had over 30 times the incidence of squamous cell cancer found in the general population. Significant increases (p less than 0.05) were also found in the incidences of respiratory cancer in males and females, pancreatic cancer in males, and kidney and colonic cancer in females. This study confirms previous reports of a dose-dependent increase in the incidence of squamous cell cancer in patients treated with PUVA.

Adolescent

Dust exposure in coeliac disease: a case-referent study.

Case series of coeliac disease show that chronic allergic alveolitis (farmers' lung) and fever reactions due to exposure to organic dust (organic dust toxic syndrome) commonly occur among subjects with coeliac disease and dermatitis herpetiformis, these being related disorders. In this case-referent study 105 cases of coeliac disease and dermatitis herpetiformis were compared with 237 referents from the general population by means of a mail inquiry regarding exposure to various environmental factors. Increased odds ratios were obtained with exposure to various farm animals and more clearly for cotton dust, although numbers were few. Animal husbandry in Sweden invariably means heavy exposure to organic dust. The fact that comparatively few persons reported dust exposure may be of doubtful validity in view of the high frequency of exposure to farm animals reported by the cases.

Adult

One year acyclovir suppression of frequently recurring genital herpes: a study of efficacy, safety, virus sensitivity and antibody response.

The efficacy of oral acyclovir 400 mg twice daily in suppressing frequently relapsing genital herpes simplex was evaluated in an open multicenter study. Seventy-one patients were treated for 12 months. During treatment, 73% of the patients were completely free of symptoms when taking the tablets continuously, and another 14% had mild symptoms such as erythema and/or itching at single occasions. An accidental treatment interruption for 2-4 days led to mild but definite herpes episodes within a few days in 5 otherwise symptom free patients. Definite herpes episodes despite acyclovir medication occurred in 3 cases (4%). No noteworthy side effects were recorded during the acyclovir treatment. After withdrawal of acyclovir, herpes relapsed within 1-4 weeks in 69% of the patients. The frequency of relapses during the following months was reported to be equal to that before the treatment period in most of the patients. Acyclovir susceptibility of the isolated herpes simplex virus (HSV) strains did not change during treatment. The mean titres of antibodies against HSV type-common glycoprotein antigen, HSV-2 type-specific antigen and varicella zoster virus antigens decreased significantly during treatment with acyclovir.

Acyclovir

Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group.

Sixty-nine patients with mycosis fungoides, plaque stage, were treated in an open study with photochemotherapy (PUVA) or the combination of oral retinoids and PUVA (RePUVA). The response rate of Re-PUVA was equal to that of PUVA, with complete remission in 73% and 72%, respectively. Remissions were obtained with fewer PUVA sessions, and with a lower UVA dosage, if PUVA was combined with retinoids. A lower UVA dosage was needed if treatment was given four times weekly in stead of twice weekly. The duration of the remissions tended to be prolonged if retinoids were given as maintenance therapy.

Adult

The importance of the coal tar bath in the Ingram treatment of psoriasis. Evaluation by evaporimetry and laser Doppler flowmetry.

The contribution of the tar component to the efficacy of the Ingram regimen in the treatment of psoriasis was assessed in 11 patients with symmetrical lesions on the upper extremities. One arm was immersed in an oil emulsion bath and the other in a coal tar bath. Whole body ultraviolet irradiation followed, and dithranol paste was applied to all lesions. Healing was assessed clinically at weekly intervals, and was found to parallel the normalization of transepidermal water loss (TEWL) as determined by evaporimetry, and the dermal blood flow as evaluated by laser Doppler flowmetry. Results obtained with coal tar baths were not significantly different from those obtained with oil emulsion. We conclude that coal tar bath additive has no advantage over oil emulsion in the Ingram regimen.

Adolescent

Function of exudate neutrophils from skin in psoriasis.

Human neutrophils harvested from skin chambers containing autologous serum in psoriatic patients were compared with peripheral blood neutrophils by examining migration, phagocytosis, and oxidative activation. Random migration was reduced in exudate cells, whereas the chemotactic response to yeast-activated serum was evident not only in blood neutrophils, but also in exudate cells. The metabolic activation of exudate neutrophils, when stimulated with formyl-methionyl-leucyl-phenylalanine and measured as chemiluminescence, was enhanced by 50-400% compared to blood neutrophils. The chemiluminescence response to phorbol myristate acetate was on the other hand reduced to 35%. In the phagocytic assay, using C3bi- and IgG-opsonized yeast particles, exudate neutrophils from non-psoriatic healthy controls showed enhanced uptake of C3bi-coated yeast compared to blood neutrophils. In psoriatics, the blood neutrophils showed enhanced C3bi-mediated phagocytosis compared to non-psoriatic control cells. No further increase in C3bi-mediated phagocytosis was then seen in exudate cells from these patients. IgG-mediated phagocytosis was in contrast to C3bi similar between blood and exudate neutrophils in psoriatics and non-psoriatic controls. These experiments show that during exudation priming of different receptor-mediated processes can occur. However, no significant difference was observed between different functional capacities in exudate neutrophils from psoriasis patients and non-psoriatic controls.

Adult

Hydration of human stratum corneum studied in vivo by optothermal infrared spectrometry, electrical capacitance measurement, and evaporimetry.

Optothermal infrared spectrometry (OTIS) is a recently introduced method for specific measurement, in vivo, of water in the skin. In the present study the method proved well suited to register the increase in water content in stratum corneum following application of emollients. The results were compared with those obtained with a commercial instrument, the Corneometer, and the two methods were found to match very closely. Neither method indicated any difference in hydration of normal skin between young and elderly women. Evaporimetry was used to detect any influence on the water barrier function of the skin following application of emollients; even though the water content of the skin was significantly higher after emollient treatment, the transepidermal water loss remained unchanged.

Adolescent

Effects of single doses of UVA, UVB, and UVC on skin blood flow, water content, and barrier function measured by laser-Doppler flowmetry, optothermal infrared spectrometry, and evaporimetry.

The effect of single doses of ultraviolet (UV) radiation was studied in 6 healthy men of skin Type III. Test areas on the forearm were irradiated with 150 J/cm2 UVA, 0.5 MED, 1 MED, and 3 MED UVB, and 1 MED UVC. Test areas and control areas were followed up for 1 month by clinical assessment, laser-Doppler flowmetry, evaporimetry, and optothermal infrared spectrometry (OTIS). UVA produced immediate erythema; the reaction appeared later with the other wavelength regions. All responses peaked after 12-24 h. The degree of erythema of UV-induced inflammation assessed visually correlated closely with the increase in skin blood flow registered with the laser-Doppler flowmeter. No increase in transepidermal water loss, indicating damage to the epidermal barrier, could be recorded by evaporimetry except on the area irradiated with 3 MED of UVB, where 4 subjects showed a moderate increase after 2 weeks. Changes in water content in the uppermost part of the epidermis, mainly in the stratum corneum, were detected by OTIS. A decrease took place that was most pronounced in the area irradiated with 3 MED UVB. This decrease in the OTIS signal is probably due to a combination of increased thickness and decreased water content of stratum corneum. We believe that these 3 noninvasive methods, especially in combination, are useful in the evaluation of different aspects of UV reactions.

Adult

Thioguanine treatment in psoriasis.

The efficacy of thioguanine in the treatment of severe cases of psoriasis is demonstrated. This treatment is valuable in selected cases of severe psoriasis in whom other treatment is ineffective or impossible due to side effects. The effect of thioguanine on psoriasis lesions appears to run parallel with depression of the bone marrow. The bone marrow toxicity has to be considered. Patients previously treated with methotrexate are very sensitive to thioguanine and close follow up is mandatory with adjustment of the thioguanine dose according to blood white cell and thrombocyte levels.

Bone Marrow Diseases