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Biomedical subjects

C N Ellis

Publications and source records attributed to C N Ellis.

At least 91 records · Page 5Linked to original sources
PubMed1990

Management of patients and side effects during cyclosporine therapy for cutaneous disorders.

Cyclosporine has been used in the experimental treatment of multiple inflammatory diseases of presumed autoimmune origin, including insulin-dependent diabetes mellitus, uveitis, rheumatoid arthritis, inflammatory bowel diseases, Graves' disease, and myasthenia gravis. In dermatology, the drug has been used successfully as primary therapy for psoriasis and psoriatic arthritis, alopecia areata, pyoderma gangrenosum, Behçet's disease, atopic dermatitis, and lichen planus. At a dose of 3 to 5 mg/kg per day, cyclosporine is well tolerated by most patients. However, because of concerns about its potential short- and long-term side effects, patients who use this drug require close monitoring. This review discusses appropriate clinical and laboratory evaluations, common and unusual side effects and their management, drugs that might alter the pharmacokinetics of cyclosporine metabolism, and criteria for dosage adjustments.

Cyclosporins↗
PubMed1990

Effects of cyclosporine on renal function in psoriasis patients.

Several prospective studies have documented the effectiveness of oral cyclosporine in the treatment of psoriasis. Despite this, the use of cyclosporine has been limited because of concern about the possibility of drug-induced renal dysfunction. We review the effects of cyclosporine on renal function.

Cyclosporins↗
PubMed1990

The erythromycin breath test as a predictor of cyclosporine blood levels.

The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.

Adult↗
PubMed1990

Changes in photo-aged human skin following topical application of all-trans retinoic acid.

Although topical applications of retinoids on rodents and humans have been shown to cause epidermal hyperplasia, a detailed study of the influence of retinoids on epidermal differentiation in vivo has not been performed. In order to assess the pharmacologic effects of chronic topical tretinoin application used to improve the appearance of patients with photoaged skin, cutaneous biopsies from 25 patients in a controlled clinical study were examined histologically and immunocytochemically. Chronic application of tretinoin causes epidermal thickening (25 of 25 samples), stratum granulosum thickening (15 of 25), parakeratosis (13 of 25), a marked increase in the number of cell layers expressing epidermal transglutaminase (13 of 25), and focal expression of two keratins, K6 (12 of 25) and K13 (8 of 25), not normally expressed in the epidermis. The morphologic changes correlated with immunohistochemical abnormalities; neither of these correlated with the subjective cosmetic response. Three major epidermal differentiation products, keratins K1, K10, and K14 were not altered, within the limits of the methods used. Thus, chronic topical tretinoin reprograms some, but not all, aspects of human epidermal differentiation in vivo.

Administration, Topical↗
PubMed1990

Mechanisms of cyclosporine A inhibition of antigen-presenting activity in uninvolved and lesional psoriatic epidermis.

To elucidate how cyclosporine A affects antigen-presenting cell subsets and their function in human skin, we studied patients with psoriasis undergoing a therapeutic trial of cyclosporine A. Immunologic parameters abnormal in psoriatic epidermis were evaluated before and early in the course of therapy. We quantitated function and numbers of skin biopsy-derived epidermal cells with potential antigen-presenting cell (APC) activity. The antigen-presenting capacity of epidermal cells from normal-appearing skin to activate allogeneic T cells was profoundly inhibited (81% decrease) 7 d after the onset of therapy (p less than 0.05). Thus, cyclosporine A therapy inhibited T-cell activation mediated by Langerhans cells in uninvolved skin. By contrast, in lesional skin epidermal allo-antigen presenting activity was only partially inhibited at this early time point (55 +/- 7% decrease) (p less than 0.01, n = 8). The percentage decrease in allo-antigen-presenting cell activity correlated with reduced clinical activity of the lesions, r = 0.84. In three patients also examined at 14 d, we found an additional 42 +/- 5% decrease between day 7 and 14. Decreased allo-antigen-presenting activity in lesional skin was not associated with a decrease in the number of CD1+ Langerhans cells or epidermal cell release of detectable amounts of cyclosporine A or other soluble factors that abrogate T-cell alloreactivity. The time course and degree of inhibition of antigen-presenting capacity within involved psoriatic skin correlated best with a significant (p less than 0.01) reduction in non-Langerhans cell DR+ leukocytes (from 3.0 +/- 1.2% to 1.0 +/- 0.6% at day 7) (r = 0.71). Cyclosporine A therapy was associated with a rapid and complete loss of HLe1-DR+ keratinocytes (94% decrease at 7 d) in lesional skin despite the skin still being quite involved with psoriasis at this point and antigen-presenting cell activity being only 60% reduced. In conclusion, cyclosporine A interferes with T-cell activation by human epidermis through at least two mechanisms: 1) in uninvolved skin, rapid inhibition of Langerhans cell-mediated activation of T cells, and 2) in lesional skin, delayed inhibition of antigen-presenting activity which appears to correlate with the time course and level of reductions in non-Langerhans cell DR+ leukocytes. The antigen-presenting activity of the latter cells appears to be cyclosporine A resistant. In psoriatic lesions, early and complete loss of DR expression on lesional keratinocytes during cyclosporine A therapy is likely due to decreased lesional T-cell lymphokine production critical for keratinocyte DR expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Presenting Cells↗
PubMed1990

Efficacy of cyclosporin A in psoriasis: a summary of the United States' experience.

Since its discovery in 1972, cyclosporin A (CyA) has been widely used in the experimental treatment of multiple inflammatory diseases considered to be of immune-mediated aetiology. In dermatology, oral CyA is most effective in the treatment of psoriasis and has been used successfully for plaque-type, pustular and erythrodermic forms of the disease. While dosages ranging from 1 to 14 mg/kg/day have been used, a starting dose of 4 mg/kg/day gives a rapid response with few side-effects. Nephrotoxicity remains the greatest concern in long-term use of the drug. Although intralesional CyA has proven effective in psoriasis, topical preparations have not. It is hoped that future research will provide effective topical formulations of CyA which are efficacious without the risks inherent in systemic administration.

Cyclosporins↗
PubMed1990

Topical tretinoin: its use in daily practice to reverse photoageing.

The effect of 0.1% tretinoin cream for the treatment of photoageing was studied in a double-blind, placebo-controlled trial. All patients applied tretinoin cream to one forearm and the vehicle cream to the other, and half of the patients also applied tretinoin cream to the face and the other half used the vehicle cream. Tretinoin treatment produced an improvement in the signs of extrinsic ageing compared with the vehicle-treated areas. Fine wrinkling was improved most, although coarse wrinkling, brown spots, tactile roughness and overall skin colour also showed clear improvement. The majority of lentigines and sun-induced freckles showed some reduction in coloration with extended treatment. It is important when using tretinoin that the treatment procedure is carefully explained to the patients and that they are warned about a retinoid reaction. It should be stressed that improvement is gradual and that regular application of the cream must continue even after improvement has been achieved. Patients should be assured that there is no evidence of carcinogenicity in humans. Although no teratogenic effects of tretinoin have been reported when applied topically, it is not advisable to use the cream when trying to conceive or when pregnant.

Administration, Topical↗
PubMed1990

The role of fish oil in psoriasis. A randomized, double-blind, placebo-controlled study to evaluate the effect of fish oil and topical corticosteroid therapy in psoriasis.

In a randomized, double-blind, placebo-controlled study, patients received 10 fish or olive oil capsules three times daily for the whole study in addition to applying betamethasone diproprionate to their psoriatic plaques for the first 3 weeks. Most patients gradually worsened upon discontinuation of corticosteroids. Using survival analysis methods, no significant difference was found between the fish and olive oil groups. The authors attempt to put the role of fish oil in the therapy of psoriasis into perspective and discuss the efficacy of fish oil when used alone versus in combination therapy.

Adult↗
PubMed1990

Psychiatric aspects of the treatment of mild to moderate facial acne. Some preliminary observations.

The improvement of acne appears to be associated with decreased depression and anxiety and greater satisfaction with aspects of body image that are generally unrelated to the appearance of the skin, ie, body shape and weight. The latter emphasizes the profound effect of the appearance of the skin upon the patient's overall body image. Our preliminary findings underline the need for larger controlled studies of psychosomatic factors among patients with mild to moderate acne.

Acne Vulgaris↗
PubMed1990

The aging face: a psychocutaneous perspective.

The cutaneous stigmata of aging may affect an individual's mental well-being, body image, and quality of life. Before proceeding with treatment, the dermatologist should take into consideration the patient's overall life situation and evaluate whether or not there is severe psychopathology and body image distortion.

Aged↗
PubMed1990

Sulfasalazine improves psoriasis. A double-blind analysis.

In an 8-week double-blind trial of sulfasalazine for the treatment of moderate-to-severe psoriasis, 23 and 27 patients received the active and placebo tablets, respectively. At the end of the double-blind phase, there were 17 assessable patients receiving sulfasalazine; 7 (41%) had marked improvement, 7 (41%) had moderate improvement, and 3 (18%) demonstrated minimal change. Only 1 patient receiving placebo demonstrated moderate improvement, whereas the rest had minimal improvement or worsening of psoriasis. When the randomization code was broken, patients receiving sulfasalazine were allowed to continue therapy for an additional 4 weeks in an open manner, while those using placebo left the study. Six of 23 patients discontinued sulfasalazine therapy during the double-blind phase because of side effects, 4 due to the development of a cutaneous eruption and 2 due to nausea. Fourteen of 17 patients, who were assessable at the end of the 8-week double-blind phase, completed the additional 4 weeks of sulfasalazine therapy. Of these 14 patients, marked improvement occurred in 8 (57%), moderate improvement in 2 (14%), and minimal improvement in 4 (29%), compared with pretherapy. The low incidence of severe side effects makes sulfasalazine a consideration for oral therapy in patients whose disease severity does not justify use of methotrexate, etretinate, or psoralen plus UV-A, but whose disease severity is too widespread for safe and practical use of topical corticosteroids.

Adult↗
PubMed1990

Oral cyclosporine in the treatment of inflammatory and noninflammatory dermatoses. A clinical and immunopathologic analysis.

Cyclosporine is known to be effective in the treatment of psoriasis. In this study, we have used oral cyclosporine (6 mg/kg per day) given for 5 to 30 weeks to 24 patients for the treatment of 12 different dermatoses. Patients with the following diseases demonstrated a marked response or total clearing: 1 patient each with pyoderma gangrenosum, pityriasis lichenoides chronica, and psoriasis of the acrodermatitis continua of Hallopeau type. Moderate to marked response occurred in both patients with epidermolysis bullosa acquisita and the patient with hidradenitis suppurativa. Minimal to moderate responses were obtained in both patients with granuloma annulare, 1 of 2 with acrodermatitis continua of Hallopeau, both patients with Darier's disease, and 1 of 6 patients with vitiligo. Little or no response was noted in both patients with sarcoidosis, all 3 patients with pityriasis rubra pilaris, 5 of 6 patients with vitiligo, 1 patient with pemphigus foliaceous, and 1 with pemphigus vulgaris. Clinical side effects were mild and transient and included dysesthesia, fatigue, hypertrichosis, nausea, and flushing. The most frequent clinically significant abnormalities were hypertension and renal dysfunction, with all factors normalizing within 1 month of discontinuation of cyclosporine therapy.

Administration, Oral↗
PubMed1990

Some psychosomatic aspects of psoriasis.

The contribution of psychosomatic factors toward the morbidity associated with psoriasis should be evaluated in the context of the patient's developmental stage and life situation. The skin, as a sensory organ, plays a critical role in an individual's physical and emotional growth in early life. The skin also plays an integral role as an organ of communication throughout life and greatly affects an individual's body image and self-esteem. If these factors are not taken into consideration, the morbidity associated with psoriasis may increase, or the patient may remain dissatisfied with treatment even in the face of clinically satisfactory treatment outcome. Some recent studies indicate that the adverse impace of psoriasis upon the quality of life can result in significant chronic stress, which may in turn exacerbate the psoriasis in a subgroup of patients. As disease-related stress is present in every patient to some degree, the dermatologist should regularly assess the psychosocial impact of the disease. Certain personality factors, such as a tendency to want the approval of others and difficulty with assertion of angry feelings, may make the patient with psoriasis more vulnerable to stress and contribute toward the stress reactivity of the disease. The presence of depression in psoriasis may modulate itch perception, exacerbate pruritus, and lead to difficulties with initiating and maintaining sleep. Helping the patient to develop assertiveness skills in addition to supportive psychotherapy may facilitate the patient's capacity to cope with the daily stresses associated with psoriasis. Treatment of depressive symptoms may prove to be a helpful adjunct in the management of pruritus and sleep difficulties in psoriasis.

Humans↗
PubMed1990

Tretinoin therapy: practical aspects of evaluation and treatment.

Tretinoin has previously been used for the treatment of acne. Recent studies, however, demonstrating the efficacy of topical tretinoin in the treatment of photodamaged skin have led to its widespread use for this entirely new indication. When prescribing tretinoin for photodamaged skin rather than acne, physicians must take into consideration a new set of issues. Patients must be selected based on their commitment to a total sun-avoidance regimen. Evaluation of photodamage must be careful and thorough prior to initiating topical tretinoin therapy. Global assessment of a patient's photodamaged skin should be made before therapy and at all follow-up visits. The patient population treated for photodamage tends to be older than that using topical tretinoin for acne; therefore, the treatment regimen must account for the different clinical and physiological characteristics of older patients' skin.

Humans↗
PubMed1990

Topical cyclosporine for oral mucosal disorders.

Topical cyclosporine may be effective in the treatment of various oral mucosal disorders. In three open trials and in one double-blind study, a topical formulation of this drug produced significant improvement in oral lichen planus. Cyclosporine blood levels were generally low in these studies and no abnormalities of laboratory values resulted during use. Of six patients with oral bullous diseases treated with topical cyclosporine, four showed a decrease in erythema, partial healing of ulcerations, and a reduction in pain. Three patients relapsed shortly after cyclosporine was discontinued. Four of eight patients with persistent aphthous stomatitis remained virtually free of ulcers during 8 weeks of topical cyclosporine therapy. These results indicate that topical cyclosporine is beneficial as a therapy for oral lichen planus and possibly other mucosal diseases.

Administration, Topical↗
PubMed1989

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A.

Since cyclosporin A (CsA) is an immunosuppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3, 7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1+ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1+DR+ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1+DR+), were also reduced after CsA, epidermal non-Langerhans CD1-DR+ cells (macrophages, activated T cells, DR- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1+DR+ Langerhans cells/non-Langerhans CD1-DR+ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗