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Biomedical subjects

G F Webster

Publications and source records attributed to G F Webster.

At least 37 records · Page 2Linked to original sources
PubMed1996

Selective calmodulin antagonists fail to inhibit phorbol ester-induced superoxide anion release from human neutrophils: effects of antifungal azole derivatives.

The ability of antifungal azole derivatives to inhibit superoxide anion release from human leucocytes and the relevance of their documented calmodulin (CaM) antagonism was investigated with respect to anti-inflammatory drug activity. Econazole, miconazole and clotrimazole were found to inhibit phorbol ester-induced release of superoxide anions from human polymorphonuclear leucocytes effectively with IC50 values in the range of 36-162 mumol/l. In contrast, bifonazole and ketoconazole produced minimal or no inhibition, thus suggesting that mechanisms other than inhibition of superoxide anion release may largely account for their clinical activity in inflammatory skin disorders. The selective CaM antagonist J-8, which was used as a reference, failed to inhibit the release process, whereas W-7 as a dual CaM/protein kinase C inhibitor induced dose-dependent inhibition. When tested on protein kinase C activity in vitro, econazole, miconazole and clotrimazole were inhibitory, but bifonazole and ketoconazole were without significant effect. It is thus concluded that inhibition of superoxide anion release reflects the ability of these drugs to inhibit protein kinase C, but not their potency to antagonize CaM. Given the role of reactive oxygen species in tissue damage by neutrophils, we propose protein kinase C, rather than CaM, as another potential target of anti-inflammatory therapy.

Animals↗
PubMed1995

Inflammation in acne vulgaris.

Recent findings suggest that an overly vigorous immune response to Propionibacterium acnes may be the fundamental problem in patients with inflammatory acne. These data and evidence for the antiinflammatory effects of acne medications are reviewed.

Acne Vulgaris↗
PubMed1995

The role of surgery in the management of uncommon skin infections.

BACKGROUND: Some infections do not respond readily to antibiotic therapy. In particular, fungi and mycobacteria often require prolonged treatment, which is expensive and prone to adverse effects. OBJECTIVE: To investigate the role of surgery in the treatment of skin infections. METHODS: Literature review. RESULTS: Infections caused by atypical mycobacteria, certain fungi, and those involving joints often respond well to surgical treatments. In several situations excision produces a higher cure rate than antibiotic treatment. CONCLUSION: Excision, drainage, or debridement has been shown to be superior to drug therapy in several infections and a reasonable alternative in others.

Aspergillosis↗
PubMed1995

Local therapy for mucocutaneous Kaposi's sarcoma in patients with acquired immunodeficiency syndrome.

BACKGROUND: Kaposi's sarcoma (KS) accounts for significant morbidity in AIDS patients. Lessons are often numerous, disfiguring, painful, and may interfere with function. Although generalized therapy is available, local treatment is often more desirable. OBJECTIVE: To summarize the available data on local therapy for KS. METHODS: Literature was searched using Medline. RESULTS: Excision, laser destruction, cryotherapy, intralesional chemotherapy, immunotherapy, and radiation therapy were compared for success rate, cost, and convenience. CONCLUSION: Intralesional therapy, cryotherapy, and radiation all have substantial advantages over excision or laser surgery. Choice of the appropriate modality varies with different sites and patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Is dermatology slipping into its anec-dotage?

In recent issues, the Archives has run a feature entitled "In the Archives a Century Ago" in which a portion of a very old article is reprinted. These articles seem often to be chosen for comic interest and make good reading, seeing how widely our forefathers missed the mark. It is even better when the author is a familiar name. How could they think such crazy things? Usually a short while after feeling so smug, one of our residents, or perhaps a visiting internist, will give me a strange look after I state some dermatologic concept and ask how we have come to such a conclusion. Sometimes, it can be tough to defend (why do so many people get "insect bite reactions" in the dead of winter?), and I am left wondering how we know what we know.

Dermatology↗
PubMed1995

Treatment of recalcitrant warts using the pulsed dye laser.

Recalcitrant warts are a common therapeutic problem. We used the 585 nm pulsed dye laser to treat flat, common, plantar/palmar, and periungual warts that had failed to respond to keratolytic or destructive therapy. Flat warts were most responsive, but all wart types had a significant response to this benign treatment modality.

Humans↗
PubMed1994

Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and the activity of protein kinase C and calmodulin.

For many years, benzoyl peroxide has been used as a topical treatment for acne. Although the drug has been shown to interfere with a variety of pathways, believed to be of importance in the aetiopathogenesis of acne, its mechanism of action is thought to be principally antibacterial. Recent circumstantial evidence suggests that protein kinase C might serve as an additional pharmacological target of benzoyl peroxide. In the present study, we investigated the effects of benzoyl peroxide on the release of reactive oxygen species, regulated by protein kinase C and calmodulin, from human neutrophils, a potentially important step in acne inflammation. Micromolar drug concentrations were found to inhibit the release of reactive oxygen species, but there was marked drug-induced cytotoxicity in neutrophils. However, when tested in cell-free assays, benzoyl peroxide displayed marginal inhibition of protein kinase C, but failed to antagonize calmodulin. Further investigations on its mechanism of action revealed non-specific interference with nucleotide binding sites. Therefore, the data presented here indicate that, in contrast with our previous findings with tetracycline derivatives, the clinical anti-inflammatory activity of benzoyl peroxide is unlikely to be mediated by protein kinase C or calmodulin. The differential interaction of drugs with protein kinase C and calmodulin might help to explain their different clinical usefulness in various degrees of acne severity.

Acne Vulgaris↗
PubMed1994

Acne. A review of optimum treatment.

Acne vulgaris is a disease of the pilosebaceous unit of the skin. It may have profound psychological sequelae. The lesions are due to abnormally adherent keratinocytes causing plugging of the follicular duct followed by accumulation of sebum and keratinous debris. This results in the formation of the primary lesion of acne, the comedo. Inflammation of comedones produces papules, pustules and nodules, which often prompt patients to seek treatment. Various effective treatments include topical anti-inflammatory, antibiotic and peeling agents, oral antibiotics, topical and oral retinoids, and hormonal agonists and antagonists. Useful combination regimens are discussed, and treatment approaches suggested. Mild cases of comedonal acne may respond to a topical retinoid or benzoyl peroxide, while inflammatory lesions benefit from topical antibiotics. More severe inflammatory acne is treated with systemic antibiotics. Recalcitrant cases often require oral isotretinoin or hormonal manipulation.

Acne Vulgaris↗
PubMed1994

Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C.

BACKGROUND AND DESIGN: Granulomatous inflammation is a common component of many diseases. In this study the ability of commonly used antibiotics to inhibit an in vitro model of granuloma formation were studied. The effect of protein kinase C inhibition in this system was also investigated. RESULTS: Ampicillin, cephalothin, metronidazole, rifampin, isoniazide, erythromycin, and clindamycin were inactive in inhibiting granuloma formation. Tetracycline, doxycycline, minocycline, and ciprofloxacin produced dose-dependent inhibition of the granuloma model in concentrations between 10(-4) and 10(-6) mol/L. The approximate order of descending potency was doxycycline equals minocycline greater than tetracycline greater than ciprofloxacin. The same drugs were tested for the ability to inhibit protein kinase C. Drugs inactive in the granuloma model had no effect on protein kinase C activity. The tetracyclines and ciprofloxacin all caused a dose-dependent inhibition of protein kinase C activity in the same order of relative potency as was found for inhibition of granuloma formation. CONCLUSIONS: These data demonstrate a previously unappreciated activity of the tetracyclines and ciprofloxacin. Inhibition of granuloma formation helps to account for the activity of these drugs in the severest forms of inflammatory acne.

Cells, Cultured↗
PubMed1993

Reflex sympathetic dystrophy: occurrence of chronic edema and nonimmune bullous skin lesions.

BACKGROUND: Reflex sympathetic dystrophy (RSD) is a poorly understood syndrome of post-traumatic pain, autonomic dysfunction, and progressive tissue atrophy. Classical descriptions of the cutaneous manifestations of RSD are usually limited to skin atrophy, vascular instability, and hyperhidrosis. OBJECTIVE: Our objective was to further delineate the cutaneous changes in RSD. METHODS: We have observed RSD-related inflammatory and bullous lesions in nine patients with active RSD. RESULTS: Eight patients had significant edema of involved skin, two patients had evidence of a pigmented purpura-like inflammatory dermatitis, and two other patients had bullae on involved skin. Ultrastructural studies on a biopsy specimen from one patient with recurrent bullae revealed a disrupted basement membrane and abnormal anchoring fibrils. CONCLUSION: Skin disease in RSD is more diverse than commonly appreciated and includes severe edema, inflammatory lesions, and a nonimmune bullous eruption.

Adult↗
PubMed1993

Direct interaction of antifungal azole-derivatives with calmodulin: a possible mechanism for their therapeutic activity.

Azole derivatives, such as ketoconazole and bifonazole, are well-established antifungal drugs. Recently, these compounds have been reported to have therapeutic efficacy also in inflammatory skin disorders. There is increasing evidence that calmodulin is involved in fungal infections as well as in inflammatory skin diseases. Therefore, we investigated the effects of various antifungal drugs on calmodulin activity, using calmodulin-dependent phosphodiesterase as an indicator for the calmodulin activity. All azole derivatives tested competitively inhibited calmodulin activity with 50% inhibitory concentration values in the low micromolar range. In contrast, antifungal drugs belonging to other chemical classes did not display inhibitory activity. Thus, this study provides evidence that direct interaction with calmodulin might contribute to the therapeutic activity of azole derivatives, particularly to their efficacy in the treatment of inflammatory skin disorders.

Antifungal Agents↗
PubMed1993

Exacerbation of psoriasis due to interferon-alpha treatment of chronic active hepatitis.

Interferon-alpha is an immune modulating drug which is indicated for the treatment of chronic viral hepatitis B and C. Several previous reports have suggested an association between treatment of patients with interferon-alpha and the development or exacerbation of autoimmune diseases. We report two patients with chronic viral hepatitis in whom treatment with interferon-alpha was associated with dramatic worsening of previously diagnosed psoriasis, necessitating discontinuation of the drug.

Adult↗