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Biomedical subjects

N J Lowe

Publications and source records attributed to N J Lowe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Microwave delivery system for lower leg telangiectasia.

BACKGROUND: The treatment of telangiectasia of the lower limbs has mainly consisted of injection sclerotherapy and the use of a variety of different lasers. Some patients do not respond well and others have a variety of local side-effects. Alternative treatments would be helpful in managing many patients. OBJECTIVE: To evaluate a microwave device for the treatment of lower limb telangiectasia less than 2 mm in diameter. METHODS: Twenty subjects were enrolled and evaluated with clinical and photographic assessment before and for up to 3 months after treatment. RESULTS: Improvement was seen in 18 of 20 patients. Two patients achieved greater than 75% improvement, six patients 51-75%, four patients 26-50% and six patients less than 25% improvement. CONCLUSION: A microwave delivery device improved lower limb telangiectasia in 18 of 20 patients.

Adult↗
PubMed1999

Optimizing therapy: tazarotene in combination with phototherapy.

Phototherapy is often used in combination with other antipsoriatic treatments in an attempt to improve efficacy and reduce patients' cumulative exposure to radiation. Although this aim has been achieved with some combinations, the additional therapies often introduce a potential risk of other tolerability and safety problems. The efficacy of tazarotene reported in clinical trials to date suggest that this drug may help to improve the efficacy of phototherapy, and perhaps reduce the ultraviolet light exposure required without introducing additional, clinically significant problems. Preliminary results from the first 10 patients in a clinical trial investigating such combination therapy are reported here. They demonstrate that the addition of tazarotene to UVB phototherapy increases the percentage of patients achieving treatment success (> or = 50% global improvement in psoriasis) from 60% to 100% at Day 81. The UVB plus tazarotene combination achieved consistently greater reductions in the elevation and scaling of difficult-to-treat psoriatic plaques than UVB phototherapy alone or UVB phototherapy plus vehicle gel. The tazarotene combination therapy also achieved initial treatment success in less than half the time needed with phototherapy alone (median of 32 vs. 67 days). Combining UVB phototherapy with tazarotene treatment appears to offer a valuable therapeutic option that is more efficacious and faster than UVB phototherapy alone.

Adult↗
PubMed1999

Lasers and adjunctive treatments for facial scars: a review.

A variety of facial scars--erythematous, pigmented, atrophic and hypertrophic--may occur as a result of trauma, surgery, burns and skin disease such as acne. Surgery with other adjunctive methods including radiotherapy, intralesional steroids and pressure therapy have shown variable results. Laser treatment has been attempted for scar revision since the 1980s. The continuous wave lasers, including continuous wave carbon dioxide (CO2), argon and Nd:YAG achieved some improvement; however, their use was limited by the inherent problems of continuous mode lasers. The pulsed dye laser has been successfully used in erythematous and hypertrophic scars. Pigment-specific Q-switched lasers have shown a good improvement for pigmented scars. Skin resurfacing lasers (both CO2 and erbium-YAG) have been used successfully to improve selected atrophic facial scars. The results may be improved by using lasers together with scar subcision and injectable or implantable fillers.

Cicatrix↗
PubMed1999

CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris.

Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

Abatacept↗
PubMed1998

The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis.

OBJECTIVE: To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques. DESIGN: Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study. SETTING: Medical center outpatient dermatology services. PARTICIPANTS: One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms. INTERVENTIONS: Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B). MAIN OUTCOME MEASURES: Treatment success and plaque elevation, scaling, and erythema vs time. RESULTS: The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily. CONCLUSION: The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.

Administration, Cutaneous↗
PubMed1998

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Adolescent↗
PubMed1998

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Antifungal Agents↗
PubMed1998

Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis.

BACKGROUND: A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed. OBJECTIVE: Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis. METHODS: Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial. RESULTS: Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy. CONCLUSION: Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.

Administration, Cutaneous↗
PubMed1998

Botulinum toxin type A for facial rejuvenation. United States and United Kingdom perspectives.

BACKGROUND: Botulinum A toxin has been well documented as a successful treatment for hyperfunctional upper facial expression lines. Currently, there are two commercial sources for botulinum toxin--Botox and Dysport. Only Botox is currently available in the United States; however, both Botox and Dysport are available in a number of European and other countries. OBJECTIVES: There are several differences between these two sources of botulinum toxin, including different potency of their dosage units. This article will review the uses of these two sources of botulinum toxin and discuss the dilution and dosing of botulinum toxin for facial expression lines. RESULTS: One unit of Botox is approximately equivalent in potency to 4 U of Dysport. CONCLUSIONS: Both commercial types of botulinum toxin can be used interchangeably with appropriate dosage selection.

Botulinum Toxins, Type A↗
PubMed1997

Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.

BACKGROUND: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Administration, Topical↗
PubMed1996

Topical calcipotriene has no short-term effect on calcium and bone metabolism of patients with psoriasis.

BACKGROUND: The biologically active form of vitamin D3, calcitriol, is effective in the treatment of psoriasis but can alter calcium metabolism. Calcipotriene is an analog of calcitriol that has low calcemic activity and aids in clearing psoriasis. OBJECTIVE: The purpose of this study was to determine the safety of topical therapy with calcipotriene particularly in relation to calcium and bone metabolism. METHODS: In a double-blind, randomized, parallel, vehicle-controlled trial, 78 adults with plaque psoriasis were treated twice daily with topical calcipotriene ointment (50 microgram/gm, maximum usage, 120 gm per week) or vehicle for 8 weeks. After a screening visit, patients were admitted to the hospital at weeks 0 (baseline), 1,2,4, and 8. Blood and urine chemistry analysis included parathyroid hormone, serum calcium, bone-specific alkaline phosphatase, urinary hydroxyproline, and 24 hour urinary calcium excretion. Bone densitometry measures were performed at baseline and week 8. RESULTS: No incidences of calcipotriene treatment-related hypercalcemia, calcium mobilization from bone, or clinically significant changes in bone density wer noted during this study. CONCLUSION: Topical application of up to 120 gm per week of calcipotriene ointment for 8 weeks is safe and effective for plaque psoriasis. There were no adverse effects on calcium and bone metabolism during this 8 week study.

Administration, Cutaneous↗
PubMed1996

Botulinum A exotoxin for glabellar folds: a double-blind, placebo-controlled study with an electromyographic injection technique.

BACKGROUND: Botulinum A exotoxin (BTX) has been used successfully to treat a variety of hyperkinetic movement disorders. BTX is also capable of reducing hyperkinetic facial lines including prominent glabellar frown lines. OBJECTIVE: The purposes of this study were to (1) confirm the efficacy of BTX in a double-blind, placebo-controlled investigation; (2) evaluate the use of an electromyogram attached to the injection needle to confirm intramuscular corrugator placement of the BTX; and (3) determine the optimum direction injection technique. METHODS: Length and depth of glabellar frown lines were measured before treatment and 4 and 12 weeks after injection of 10 units of BTX or saline solution. RESULTS: Patients treated with BTX had a highly significant reduction in depth and length of glabellar frown lines compared with control subjects. CONCLUSION: BTX appears to be effective and safe for reduction of glabellar frown lines.

Botulinum Toxins, Type A↗
PubMed1996

Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure.

BACKGROUND: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known. OBJECTIVE: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects. METHODS: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function. RESULTS: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension. CONCLUSION: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.

Adult↗
PubMed1995

Low doses of repetitive ultraviolet A induce morphologic changes in human skin.

Repetitive exposure of skin to sunlight is known to result in dermatoheliosis, characterized by photoaging and carcinogenesis. It has been demonstrated previously that relatively large amounts of ultraviolet (UV) A can produce photodamage and it is believed that UVB plays a major role in the induction of photodamage and photocarcinogenesis. The study reported here determines the cutaneous effects of minimal erythemal amounts of solar-simulated UV radiation as well as suberythemal and minimal erythemal doses of UVA. Previously non-sunexposed human skin was irradiated twice weekly for 24 weeks. Biopsies were obtained 12, 24 and 36 weeks after the initial irradiation and assessed for both epidermal and dermal alterations. Dermal elastic tissue content was measured via computerized image analysis. All UV treatment regimens produced observable epidermal and dermal changes. These alterations were observed after only 12 weeks of twice-weekly irradiation and were still evident 12 weeks after the final irradiation. Interestingly, UVA irradiation produced a decrease in elastic tissue content whereas solar-simulated UV produced a slight increase. Most notable were the changes produced by the suberythemal dose of UVA. Surprisingly, this relatively low UVA dose produced a reduction in elastic tissue content. The results of this investigation demonstrate that small amounts of UVA or solar-simulated UV are capable of producing cutaneous photodamage. These findings suggest that even suberythemal doses of repetitive UVA may lead to photoaging of the skin and that there is a need for daily broad spectrum UV protection.

Adult↗