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Biomedical subjects

S Wadskov

Publications and source records attributed to S Wadskov.

At least 19 recordsLinked to original sources

Plasma and synovial fluid cAMP in patients with rheumatoid arthritis.

cAMP was measured in plasma and synovial fluid from 11 patients suffering from rheumatoid arthritis with a specific protein-binding assay. Plasma and synovial fluid values were 17.0 +/- 6.8 pmol/ml and 8.3 +/- 3.7 pmol/ml, range 5-28 pmol/ml and 5-16 pmol/ml, respectively. No correlation could be established between plasma and synovial fluid levels, plasma and disease activity, or synovial fluid and disease activity, as judged by Lansbury's index. It is concluded that it seems unlikely that synovial fluid cAMP is derived solely from plasma and that no simple relation exists between cAMP in plasma and synovial fluid and total disease activity.

Adult

DNA in psoriatic epidermis.

An electron microscopic technique has been used to visualize crosslinks after total denaturation on DNA isolated from epidermis and dermis in patients with psoriasis treated with 8-methoxypsoralen (8-MOP) and irradiation with ultraviolet light at 360 nm (PUVA treatment). This technique facilitated accurate measurements of the number and density of DNA interstrand crosslinks. 30 biopsies from 14 patients were studied and a total of 9503 DNA molecules were scored in the electron-microscope, 6 patients were treated topically with 8-MOP and 10 were on systemic treatment. Two of the patients on topical treatment had previously been on systemic treatment. 1% of all DNA molecules contained 3 or more cross-links. The overall frequency of cross-links was almost identical in the epidermis (1.1%) and in the dermis (0.9%) and, furthermore, virtually the same in patients on topical and systemic PUVA treatment. The total number of crosslinks was of the same magnitude as that previously found in normal human skin. (V. Bohr et al., Acta Dermatovener, in press.) No significantly increased damage of the genetic material (DNA) was demonstrated in our study as a consequence of the PUVA treatment using 8-MOP. We have previously shown (V. Bohr & A. Lerche, Biochim Biophys Acta, in press) that 8-MOP induced crosslinks after irradiation at 360 nm in an in vitro system of pure DNA. In this system a correlation was established between the density of crosslinks formed and irradiation time, concentration of 8-MOP, and irradiation intensity.

DNA

DNA interstrand crosslinks visualized by electron microscopy in PUVA-treated psoriasis.

An electron microscopic method has been used to visualize crosslinks after total denaturation of DNA isolated from epidermis and dermis in patients with psoriasis treated with 8-methoxypsoralen (8-MOP) and irradiation with ultraviolet light at 360 nm (PUVA treatment). This technique enabled accurate measurement of the number and density of DNA interstrand crosslinks. 30 biopsies were studied and a total of 9503 DNA molecules were scored in the electron microscope. 6 patients were treated topically with 8-MOP and 10 were on systemic treatment and biopsies were obtained immediately after irradiation. 1% of the total DNA molecules examined contained 3 or more crosslinks. The overall frequency of crosslinks was almost identical in the epidermis (1.1%) and in the dermis (0.9%) and, furthermore, virtually the same in patients on topical and systemic PUVA treatment. The total number of crosslinks was of the same magnitude as those previously found by us in normal human skin. Thus, though the formation of interstrand DNA crosslinks can be considered as an indicator of damage of the genetic material, we were unable to demonstrate this as being a consequence of PUVA treatment using 8-MOP.

Adult

Cyclic AMP and psoriasis once more.

Imbalanced cyclic nucleotides are implicated as an underlying pathogenetic mechanism in psoriasis, but conflicting data on the levels of cAMP in psoriatic tissue have been obtained by different laboratories. Using heat separation and a competitive protein binding cAMP assay, a noticeably decreased epidermal level of cAMP was detected in newly formed guttate lesions in 10 patients with psoriasis (involved: 4.32 +/- 1.06 pmol/mg dry weight mean +/- S.E.M.). uninvolved: 7.97 +/- 1.63 pmol/mg dry weight mean +/- S.E.M.). In proliferative rat skin, bidirectional alterations in cAMP levels are known to occur. On the basis of present observation, we assume that the conflicting data hitherto obtained in psoriatic tissue similarly may merely reflect the various levels of cAMP at different developmental stages.

Adolescent

Acquired zinc deficiency dermatosis in man.

We encountered two cases of acquired zinc deficiency. In one of the patients the state was due to alcoholism with liver cirrhosis and pancreatitis, and in the other patient it was attributed to a small intestine bypass operation for obesity. The skin symptoms included hair loss, acrodermatitis, and widespread eczema craquelé (asteatosis). The cutaneous manifestations of zinc deficiency seem to constitute a characteristic syndrome that might be helpful in recognizing manifest zinc-deficient states in man.

Acrodermatitis

Dose-dependent effect of topical corticosteroids on blood flow in human cutaneous tissue.

In seven healthy subjects the dorsum of the hand was treated with beta-methasone valerate cream in increasing concentrations, from 0.1 to 1.0%, and with hydrocortisone butyrate 0.1% with or without plastic occlusion. Under conditions of controlled room temperature, blood flow in treated, placebo-treated, and untreated cutaneous tissue was measured using the local 133Xenon wash-out technique. Placebo creams did not affect cutaneous blood flow, but beta-methasone valerate 0.1% reduced blood flow and 1.0% increased it. An increase in blood flow was also observed after use of hydrocortisone butyrate under plastic occlusion. The results indicate a dual effect of potent corticosteroids on cutaneous blood flow.

Administration, Topical

Determination of cyclic AMP in heat-separated human epidermal tissue.

Heat separation is introduced as a simple, reliable and quick method for obtaining pure epidermis for cyclic AMP analysis. Heating at 60 degrees -65degrees C for 10 min resulted in a distinct separation of epidermis from dermis. The level of cyclic AMP in epidermal tissue from 9 patients was 3.93 +/- 0.31 pmol per mg dry weight. The inter- and intra-assay variations were 10.3% and 8.8%, respectively. The coefficience of variation in eight biopsies from the same piece of skin was 16.2% The sensitivity of the assay was 0.07 pmol. Recovery analyses revealed that 80.5% of labelled cyclic AMP was refound after extraction and purification procedures. Addition of unlabelled cyclic AMP resulted in a recovery of approximately 100%. The specificity of the assay was high without interference from several nucleotides and the validity was confirmed by zero values obtained after addition of phosphodiesterase or charcoal.

Adolescent

Increased 133xenon washout from cutaneous tissue in generalized scleroderma indicates increased blood flow.

Blood flow in cutaneous tissue of the dorsum of the hand was measured by the local 133Xenon washout technique in 18 normal persons and in 26 patients suffering from generalized scleroderma of the acrosclerosis types. Flow values calculated from the accepted blood--tissue solubility coefficient (lambda) were 8.6 +/- 0.4 S.E.M. ml/100 g X min in normals and 14.5 +/- 1.1 ml/100 g X min in sclerodermic skin (i.e. increased by 69%). The difference was significant (p less than 0.001). Blood flow values in sclerodermic skin were directly proportional to the degree of dermal sclerosis. As lambda in sclerodermic skin is probably decreased due to a decreased fat content, it may not be correct to interpret these results as evidence of increased blood flow. A "worst case" was constructed in calculation of lambda using zero fat content for sclerodermic skin. Flow value was now 12.3 +/- 1.1 S.E.M. ml/100 g X min for sclerodermic skin, an increase of 43% compared with normal skin. It is probably only justified to use this "worst case lambda" in the group of severely involved cases of scleroderma. In these patients it yielded a flow value of 17.8 +/- 3.1 (N = 6) which, when compared with the flow value for normal skin, indicates an increase by 100% of the blood flow in severely involved sclerodermic skin.

Adult

DNA interstrand crosslinks in normal human skin visualized by electron microscopy.

Normal human skin was investigated for DNA interstrand crosslinks by a denaturation electron microscopic method. Skin biopsy materials from the thighs of 8 healthy volunteers were separated into epidermis and dermis. DNA from each layer was isolated, purified and studied in the electron microscope. The presence of DNA interstrand crosslinks in normal human skin was demonstrated. The number of crosslinked DNA molecules and the density of crosslinking within the molecules were determined. Crosslinks were found in 0.8% of the scored molecules and were located almost exclusively in epidermal DNA. The intramolecular density of crosslinking showed a wide range of variation in each volunteer and between the volunteers.

Adult

Electron microscopic cytochemical demonstration of adenyl cyclase activity in psoriatic epidermis.

Isoproterenol and sodium fluoride stimulated adenyl cyclase activity was detected in epidermal tissue from 2 patients with untreated psoriasis by an electron microscopic cytochemical technique. Adenyl cyclase activity was present on the outer surface of the cell membranes, predominantly in the basal cells and in the 4-5 lower Malpighian cell layers, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The precipitates (lead-PPi complexes) after isoproterenol stimulation were larger and fewer in number than those seen after sodium fluoride stimulation. Isoproterenol stimulation was abolished by propranolol. Neither the uninvolved epidermis from the 2 patients with psoriasis nor the normal skin from 2 volunteer individuals showed any difference from the psoriatic epidermis.

Adenylyl Cyclases

Studies on 133Xe wash-out from human skin: quantitative measurements of blood flow in normal and corticosteroid-treated skin.

Blood flow was measured by the 133Xe technique in normal and corticosteroid-treated skin. Epicutaneous and intracutaneous methods of tracer application were compared in normal skin. The two labeling methods were equally suitable for measuring cutaneous blood flow provided calculations in both cases were based on a biexponential resolution of the wash-out curve in its cutaneous and subcutaneous components and provided the traumatic hyperemia phase was considered, when intracutaneous application of the tracer was used. Results were invalidated if calculations were based on initial slope of the wash-out curves.Topical application of beta-methasone valerate in a reduction in cutaneous blood flow as measured by the intracutaneous technique with curve resolution, whereas no effect could be demonstrated when calculations were based on the initial slopes of the curves. The 133Xe technique is a simple and reliable method for measuring cutaneous blood flow, which might prove useful in estimations of penetration ability and potency of topical corticosteroids.

Administration, Topical

Local regulation of blood flow in subcutaneous tissue in generalized scleroderma.

The effect of orthostatic changes in vascular transmural pressure on blood flow in subcutaneous tissue was studied in 10 patients with the acrosclerotic type of generalized scleroderma. Blood flow was measured on the back of the hand by the local 133xenon washout technique. The blood flow remained constant when the hand was elevated 20 cm above the jugular notch, indicating that there is autoregulation of blood flow, When the hand was lowered 40 cm below by 50% observed in normals. Thus, intrinsic vascular reactions responsible for the autoregulator response are present, whereas the normal "vasoconstrictor response" to an increase in venous transmural pressure is almost abolished in tissues with sclerodermic changes. The abolition of the vasoconstrictor response is probably due to sympathetic neuropathy associated with the sclerodermic changes.

Aged

Oral zinc sulphate therapy for acne vulgaris.

A double-blind controlled clinical trial was performed to evaluate the effect of oral zinc sulphate, 0.6 g daily, on acne vulgaris. Twenty patients received zinc sulphate tablets and 19 were given placebo tablets. Thirteen of the zinc group and 12 of the placebo group received their medication throughout a 12-week period, while the remaining patients were treated for 4 or 8 weeks. In all patients the numbers or papular and pustular acne lesions on the face and the back were significantly reduced, while larger infiltrates remained practically unaltered during the trial, which was performed from March through May 1975. No statistically significant difference in the improvement of the groups was demonstrable. Pretreatment serum zinc values, which were normal in all patients, rose significantly in the zinc group as well as in the control group, but the increase in the former was significantly higher. The negative therapeutical results might be attributable to the limited number of patients or related to the zinc dosage. Furthermore, the results might have been influenced by the unexplained rise in serum zinc values in the control group. A possible weak beneficial effect of zinc might also have been camouflaged by the seasonal variation in the severity of acne which was noted in this study.

Acne Vulgaris

Electron microscopic cytochemistry for demonstration of sodium fluoride sensitive adenyl cyclase in normal human epidermis.

Adenyl cyclase activity in normal human epidermis was detected by an electron microscopic cytochemical technique. The sodium fluoride sensitive receptors were demonstrated on the outer sheath of the cell membranes. Adenyl cyclase activity was demonstrated in the basal cells and in the 4-5 lower layers of the Malpighian cells, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The findings confirm and extend previous biochemical studies and provide a clue to the conception of the adenyl cyclase enzyme as a transmembrane arranged system.

Adenylyl Cyclases

Penicillamine-induced pemphigus foliaceus.

A 61-year-old man suffering from active generalized scleroderma developed pemphigus foliaceus after 9 months of D-penicillamine therapy, 900-1200 mg daily. At the same time, he developed proteinuria. Upon discontinuation of the drug, the proteinuria quickly resolved, but the bullous disease was still active one year later, with development of fresh blisters and intercellular deposits of immunoglobulin G and complement C3. The theory is proposed that D-penicillamine alters the epidermal cement substance, rendering it antigenic and thus initiating a vicious circle.

Humans

Acquired hypertrichosis lanuginosa. A skin marker of internal malignancy.

A 54-year-old woman had acquired hypertrichosis lanuginosa. She developed excessive growth of lanugo-like hair all over her body two years prior to the sudden appearance of a rapidly growing, localized, solid mammary tumor. Of 12 published cases, nine have been associated with an internal malignant neoplasm and obviously, as in the present case, the cutaneous symptoms may serve as a skin marker by preceding the tumor diagnosis for up to two years.

Adult

Cutaneous reactions to propranolol (Inderal).

Six patients wit psoriasiform cutaneous eruptions that developed during long-term therapy with propranolol (Inderal) have been studied. The cutaneous changes closely resembled those seen during treatment with practolol (Eraldin). The duration of treatment before the rash was recognized averaged 10 months, which is about the same latency period as in patients with practolol-induced exanthemas. The exanthemas disappeared gradually within 1-5 weeks after treatment with propranolol had been stopped. In 4 of 5 patients the skin eruptions reappeared within 2-4 days after oral challenge with propranolol. In the fifth patient, who developed a rash after challenge with practolol and severe abdominal colics after challenge with oxprenolol, no further provocation tests with propranolol were attempted. Skin biopsies obtained from 3 patients showed a microscopical picture similar to that seen in practolol exanthemas. The pathogenetic mechanism responsible for these adverse cutaneous reactions is unknown. However, since the possibility exists, that these changes may be caused by blockade of the epidermal beta-receptors, it is recommended that all patients receiving beta-blocking drugs should be examined carefully for similar adverse reactions. Special attention should be drawn to the reversible skin changes, since during treatment with practolol these have often preceded serious complications from other organs.

Aged