Gilles J. Lauzon

Tobacco and the skin

Smoking negatively impacts the health of the skin as it does every organ system. This contribution reviews the effect of cigarette smoking on wound healing, wrinkling, and aging of the skin, skin cancer, psoriasis, and other inflammatory skin diseases, hidradenitis suppurativa, acne, alopecia, lupus erythematosus, polymorphous light eruption, and tobacco-associated oral lesions. Dermatologists need to encourage their patients to discontinue this deleterious habit.

Toxicity of combinations of arabinosylcytosine and 3-deazauridine toward neoplastic cells in culture

Abstract The antiproliferative effects of 3-deazauridine and arabinosylcytosine toward cells in culture (HeLa and RPMI 6410 lymphoblastoid cells) were potentiated when the agents were present together. The conversion of arabinosylcytosine to nucleotide metabolites in RPMI 6410 cells was greatly enhanced in the presence of deazauridine: this enhancement is thought to be the basis of the potentiation in antiproliferative activity. These drug combination effects did not occur in two RPMI 6410 sublines which were resistant to deazauridine and deficient in uridine kinase activity.

A population-based study of cutaneous melanoma in Alberta, Canada (1993-2002)

BACKGROUND There is evidence to suggest that melanoma incidence rates continue to rise in Canada and the United States. OBJECTIVE Our objective was to determine cutaneous melanoma trends from 1993 to 2002 in the province of Alberta and to compare the results to previously published provincial analyses for the decade of 1967-1976. METHODS A retrospective study of 3479 patients with cutaneous melanoma diagnosed in Alberta between 1993 and 2002 was conducted. Estimates of relative survival compared the survival of melanoma patients with the Alberta population to derive the likelihood of surviving melanoma in the absence of other causes of death. Further comparison to published Canadian data was also conducted. RESULTS For the period 1993-2002, the annual melanoma age-standardized incidence rates per 100,000 person-years ranged between 11.1 and 15.9 and between 9.8 and 14.1 among men and women, respectively. These rates are considerably higher than the previously reported (1976) highest Alberta incidence rates of 4.1 and 4.8 in men and women, respectively. The rates increased slightly for the period 1993-1999 with an average annual percentage change of +3.5%, but appeared to decrease for the interval 1999-2002 with an average annual percentage change of -6.4%. The majority of the tumors were less than 1.0 mm in thickness for both genders. On univariate analysis the following parameters were associated with decreasing patient survival: male gender, increasing age, head and neck tumors, Clark level of invasion, and Breslow tumor thickness. Multivariate analysis demonstrated that the strongest determinant of survival was Breslow tumor thickness. LIMITATIONS Melanomas in-situ were not included in this study. CONCLUSIONS Although melanoma incidence rates in Alberta are higher than previously reported, the incidence rates over the study period of 1993 to 2002 appear to have leveled and may in fact be declining over the past several years.

ISA247: quality of life results from a phase II, randomized, placebo-controlled study.

Background: Psoriasis is a chronic skin condition that can negatively affect a patients quality of life (QoL), often hindering social functioning. ISA247, a novel psoriatic agent, has shown clinical efficacy in moderate to severe psoriasis sufferers, but its effect on QoL is currently not reported. Objective: The objective of this study was to assess the effect of ISA247 on the QoL in patients with stable, plaque-type psoriasis. Methods: A phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study assessed the effects of ISA247 doses of 0.5 mg/kg/d (n = 77) or 1.5 mg/kg/d (n = 83) compared with placebo (n = 41) for 12 weeks. QoL was assessed using the Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) scales. Results: ISA247 treatment (pooled groups) significantly improved QoL scores as assessed by both the DLQI and the PDI compared with those receiving placebo (p < .05). Treatment with the higher dose of 1.5 mg/kg/d demonstrated a significantly greater response to many of the QoL scales compared with the 0.5 mg/kg/d group (p < .05). Conclusions: ISA247 appears to improve the QoL while also providing effective treatment for chronic, moderate to severe, plaque-type psoriasis.

Acrokeratosis paraneoplastica (Bazex syndrome) presenting in a patient with metastatic breast carcinoma: possible etiologic role of zinc.

Background: Bazex syndrome (acrokeratosis paraneoplastica) is a rare paraneoplastic syndrome that usually occurs in males over 40 years old and is particularly associated with squamous cell carcinoma of the upper aerodigestive tract and adenopathy above the diaphragm. Objective: The objectives of our article are (1) to describe a unique case of acrokeratosis paraneoplastica and (2) to review the current literature regarding skin findings, commonly associated neoplasms, and treatment options relative to this condition. Patient: We describe a 68-year-old female with lobular breast carcinoma, complicated by local and distant recurrences, who presented with a 1-year history of prominent acral skin and nail changes. Results: Our patients clinical skin findings improved significantly following treatment and partial remission of her underlying malignancy. Conclusions: Our patient represents one of few females described with this syndrome, which is especially rare in association with lobular breast carcinoma. Further, the patients presentation is unique as she was discovered to demonstrate laboratory findings consistent with coexistent porphyria cutanea tarda and relative zinc deficiency.

Cell cycle arrest as a basis of enhancement of 1-β-d-arabinofuranosylcytosine anabolism in human lymphoblastoid RPMI 6410 cells cultured with 3-deazauridine☆

Abstract The antiproliferative effect of 1-β- D -arabinofuranosylcytosine (araC) on RPMI 6410 cells in culture was potentiated in the presence of 3-deazauridine (DU). When the culture medium contained DU, proliferation ceased and cells did not progress in the replication cycle beyond early S phase. When cells from such DU-treated cultures were transferred to DU-free medium containing Cyd, a rapid, partially synchronous resumption of DNA synthesis occurred. Under these circumstances, the activity of dCyd kinase, assessed using araC as substrate, was enhanced in unfractionated extracts of DU-treated cells relative to extracts of untreated cells. It is suggested that the presence of DU in culture medium stopped the progression of cells through the replication cycle, arresting them in an araC-sensitive portion of S phase, and that the enhanced ability of DU-treated cells to anabolize dCyd and araC derived, at least in part, from the accumulation of cells in S phase, a portion of the cell cycle in which dCyd kinase is elevated.

Neoral® in the Treatment of Psoriasis: Consensus Treatment Guidelines

Background: The efficacy of cyclosporine in the treatment of psoriasis is well-recognized. A new microemulsion formulation of cyclosporine, Neoral®, has become available and will replace the original formulation, Sandimmune®. Objectives: In view of the new clinical experience with Neoral and changes in clinical practice, an expert panel was convened to review the treatment guidelines and make new recommendations for its use in the treatment of psoriasis. Results: Compared with the original formulation, Neoral is more rapidly absorbed and there is less intra- and interpatient variation in bioavailability. In clinical trials, Neoral had a faster onset of action than Sandimmune at equal doses; efficacy and safety profiles were comparable. Conclusion: Neoral is indicated in patients with severe psoriasis in whom systemic therapy is justified. Careful baseline clinical and laboratory evaluation is mandatory prior to initiation of Neoral therapy. The therapeutic goal is to maintain substantial improvement with the lowest possible dose of cyclosporine. If possible, intermittent therapy is preferable. Guidelines for monitoring and management of adverse effects are presented.