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Biomedical subjects

S Shuster

Publications and source records attributed to S Shuster.

At least 37 records · Page 2Linked to original sources

Contact dermatitis with negative patch tests: the additive effect of allergens in combination.

We deduced on theoretical grounds that conventional patch testing would be inadequate for the detection of sensitivity to multiple allergens. Fourteen patients with positive patch tests to two unrelated allergens were studied and the response to those two allergens was measured when tested singly or in combination, using 10 different pair combinations from 15 common allergens. With serial dilutions in chloroform (14 patients) and paraffin (four patients), the response was related to the log-dose of the allergen, and change in skin-fold thickness corresponded well with clinical grading. Single allergens diluted below the threshold for a patch-test response gave a response when given in combination, the threshold for a response to one allergen being lowered by the presence of another. On the linear part of the dose-response curves the response to the mixture of allergens was additive, the combined response being the sum of the individual components. Approaching the plateau region the response to the combination was greater than to the individual allergens but less than the sum of the single responses. The same results were obtained with allergens in paraffin. We conclude that conventional single allergen patch testing by itself is inadequate for the diagnosis of contact dermatitis.

Allergens

The permissive effect of sebum in seborrhoeic dermatitis: an explanation of the rash in neurological disorders.

The hypothesis that sebum permits the growth of Pityrosporum ovale, and hence the development of seborrhoeic dermatitis, was tested by observing whether a reduction of sebum production by isotretinoin would improve the disorder. In 10 male patients with seborrhoeic dermatitis, treatment with isotretinoin for 6 weeks reduced the mean sebum excretion rate by 70% and improved the severity of the rash, but with a site difference in magnitude of response. It is concluded that the residual pool of sebum is important for the growth of P. ovale and that, within the physiological range, sebum has a permissive effect on the growth of this yeast. Variation in the pools of residual sebum explains a number of features of the disease such as site of involvement and greater prevalence in males than females. The pathological increase in the residual pool of sebum due to immobility explains the frequent occurrence of seborrhoeic dermatitis in patients with a variety of neurological disorders.

Adult

Relapse rates in moderately severe chronic psoriasis treated with cyclosporin A.

Seventeen patients with chronic psoriasis were given cyclosporin A (CsA) 5 mg/kg per day. Twelve patients cleared within 3 months and their relapse rate, 41% at 6 months, was not significantly different from that previously reported with dithranol or PUVA. This pilot study also suggests that continuing CsA for up to 4 weeks after clinical clearance confers no advantage with regard to relapse. Significant adverse effects on renal function and blood pressure did not occur.

Adult

Control and function of sebaceous glands.

This review describes the various types of sebaceous glands, their locations, and where possible their different functions. All sebaceous glands are similar in structure and secrete sebum by a holocrine process. However, the nature of this secretion and the regulation of the secretory process seem to differ among the various types of glands. Methods for measuring sebum secretion and assessing sebaceous gland activity are also described. The area of major interest during the last 20 years has undoubtedly been the mechanisms that control sebaceous gland function. Most studies have focused on the endocrine control and in particular on the role of androgens and pituitary hormones, although evidence suggests that nonendocrine factors may also be important. However, many questions remain and during the next few years attention will certainly be given to the role of retinoids and their mode of action in the treatment of acne.

Animals

Antihistamines in the treatment of urticarial disorders.

A number of studies of the effects of antihistamines on chronic idiopathic urticaria and itch are reviewed. In chronic idiopathic urticaria, terfenadine has been shown to control the number, size, and duration of skin whealing as well as itch. Likewise, in chronic dermatographic urticaria, the minimal force required to produce whealing is increased, while severity of itch is decreased following treatment with terfenadine. In both conditions, however, wheal formation is not completely inhibited, suggesting the involvement of a mechanism unrelated to histamine. In nonurticarial disease in which histamine is not involved in the pathogenesis, antihistamines appear to work as antipruritics, but by a sedative-related property and not by antagonism of H1-receptors.

Astemizole

Cyclosporine in dermatology.

The entry of Cs into dermatology has been remarkable. It is too soon to say that the consequences will be revolutionary, but if the drug continues with its present promise and if toxicity does not prove a problem it could indeed promote a therapeutic revolution. In addition to this, Cs is likely to induce many new thoughts about possible mechanisms in dermatology and perversely in immunology, especially if it transpires that the mechanism of action of the drug is local and on an effector pathway. Thus it is too soon to predict what might be the place for Cs in dermatology. For the moment it is clear that there is an immense area in which a good deal of work has to be done to know whether the drug will fulfill its very great promise and the further prospect too that new analogues and topical preparations may take the therapeutic possibilities even further.

Cyclosporins

A comparison of structure-activity relationships within alpha-MSH on melanophores of Anolis carolinensis and Rana pipiens.

We have compared the structure-function relationship of the tridecapeptide alpha-melanocyte stimulating hormone (alpha-MSH) on the melanophores of the lizard Anolis carolinensis and the frog Rana pipiens by determining the melanosome-dispersing potency of 15 shorter peptide sequences and 8 substituted alpha-MSH analogues. Major differences were found between the lizard and the frog in their response to alpha-MSH peptide fragments and analogues. In Anolis, the sequence Ser-Tyr-Ser- is not as important for the pigmentary response as in Rana since alpha-MSH-(4-13) was nearly as potent (89%) as alpha-MSH-(1-13) (100%), whereas in Rana alpha-MSH-(4-13) potency was reduced to 7.5%. In addition, loss of potency due to removal of residues Pro and Val was more marked in Rana (alpha-MSH-(1-11) = 0.1%) than in Anolis (alpha-MSH-(1-11) = 1%), suggesting that this C-terminal sequence is necessary for pigmentary activity in the frog melanophore. These results together with those of other peptide fragments and analogues have led us to define the minimal pigmentary sequence of alpha-MSH as alpha-MSH-(4-12) in Anolis in contrast to alpha-MSH-(1-13) in Rana. This suggests that Anolis and Rana alpha-MSH receptors recognise different message amino acids of the alpha-MSH peptide sequence even though the final response (melanosome dispersion) is the same.

Amino Acid Sequence

The effect of topical dimethindene maleate on weal reactions.

The topical effect of the histamine H1-receptor antagonist dimethindene maleate on the wealing response to intradermal histamine, compound 48/80 and house dust mite antigen was studied in 16 subjects using a double-blind procedure. The mean reduction in weal area +/- s.e. mean was 44% +/- 13%, 43% +/- 13% and 31% +/- 13% for histamine, 48/80 and antigen respectively. We conclude that dimethindene maleate is a moderately potent H1-receptor antagonist, and that the inhibition of the 48/80 and house dust mite induced weals is accounted for by the antihistaminic effect of dimethindene maleate.

Adult

Effect of arachidonic acid on anthralin inflammation.

1 The effect of topical arachidonic acid on anthralin inflammation was studied using sequential measurements of erythema (reflectance photometry) and oedema (calipers). 2 Topical arachidonic acid in concentrations which produced a small short-lived inflammatory response greatly augmented the initial phase and depressed the later phase of the inflammatory response to anthralin. 3 The initial augmentation was inhibited by concomitant administration of alpha-tocopherol. 4 It is suggested that free radical formation by anthralin has a direct action on membrane substrates such as arachidonic acid forming inflammatory products by a non-enzymic process.

Administration, Topical

Lack of effect of topical indomethacin on psoriasis.

Topical 1% indomethacin had no effect on chronic stable plaque psoriasis in an open controlled study using subjective clinical scores nor in a randomised double-blind inert base controlled study using both subjective and objective measurements of lesional response; nor did it initiate or affect the development of psoriasis after cold injury. Previous studies are reviewed and it is concluded that the evidence does not support the hypothesis which relates psoriasis to eicosanoids produced by lipoxygenase activity.

Administration, Topical

The effect of nedocromil on weal reactions in human skin.

1. Nedocromil 2% iontophoresed into human skin had no effect on wealing produced by intradermal histamine, 48/80 or house dust mite antigen. 2. Iontophoresis of 0.002-2% nedocromil itself resulted in dose-related wealing. 3. This wealing was reduced by 62 +/- 8% s.e. mean by the H1-receptor antagonist terfenadine which decreased histamine wealing by 68 +/- 2% s.e. mean. 4. Nedocromil may therefore act as a weak agonist on a skin mast cell receptor concerned with histamine release.

Adult

Isotretinoin and serum lipids: studies on fatty acid, apolipoprotein and intermediary metabolism.

Thirteen patients with severe acne were treated for 16 weeks with 1.0 mg/kg/day isotretinoin. There were significant increases in serum cholesterol (P less than 0.02), triglycerides (P less than 0.02) and apolipoprotein B (P less than 0.02). No changes were found in serum apolipoprotein A-1, non-esterified fatty acids (NEFA), carnitine, lactate, pyruvate, glycerol, alanine, beta-hydroxybutyrate, glucose or insulin. We therefore found no evidence that the hyperlipidaemia of isotretinoin therapy is due to increased fluxes of NEFA from adipose tissue to the liver, although we cannot exclude the possibility that there are changes in the proportion of NEFA being esterified to triglyceride or undergoing beta-oxidation. We suggest that the hyperlipidaemia induced by isotretinoin may be due to an increase in circulating lipoprotein from increased production or impaired catabolism.

Acne Vulgaris

Reduction of anthralin inflammation by potassium hydroxide and Teepol.

Application of 1% potassium hydroxide (KOH) reduced subsequent development of anthralin inflammation without loss of its therapeutic effect on psoriasis. Teepol had a similar but smaller effect on subsequent development of inflammation. The action of KOH appears to have resulted from enhanced oxidation of anthralin to inactive products and the action of Teepol to have increased anthralin solubility and removal. The effect of KOH and Teepol decreased with time after anthralin application and both were ineffective by 24 h, indicating that anthralin persists on the skin in an active form for up to 24 h after a single application. The reduction of anthralin inflammation without loss of therapeutic effect is potentially useful in short contact anthralin therapy.

Adolescent

Treatment of seborrhoeic dermatitis with ketoconazole: II. Response of seborrhoeic dermatitis of the face, scalp and trunk to topical ketoconazole.

A randomized, double-blind, placebo-controlled study was made of 2% ketoconazole cream and shampoo in 20 patients with seborrhoeic dermatitis of the face. Sixteen also had seborrhoeic dermatitis of the scalp and five had seborrhoeic dermatitis of the chest or back. Responses were measured by clinicians and patients independently using a grading system and linear analogue scales, respectively. Face and scalp lesions, assessed by both patient and clinician, showed a significant improvement or complete clearance in the group treated with ketoconazole. The patients who had seborrhoeic dermatitis of the chest or back and were treated with ketoconazole also improved. There was no improvement with placebo. This study provides further evidence for the aetiological role of pityrosporon yeasts in seborrhoeic dermatitis and of the efficacy of topical ketoconazole in its treatment.

Administration, Topical