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Biomedical subjects

V P Werth

Publications and source records attributed to V P Werth.

At least 19 recordsLinked to original sources
PubMed2001

Preserving medical dermatology. A colleague lost, a call to arms, and a plan for battle.

Change within dermatology as a clinical discipline is expected and inevitable. However dermatology may change as a medical specialty in the new millennium, there will still be patients with medical dermatologic disease whose optimal care will depend on skin disease specialists' having the highest level of training and experience in medical dermatology. Dermatologists who have subspecialized in medical dermatology will provide the role models for new generations of dermatologists, perform the patient-oriented research, and care for the more complicated patients. Thus, if during its evolution, dermatology loses the ability to train and support medical dermatologists, it will be weakened as the discipline that can best care for skin disease. Clearly, the loss of talented academicians such as the person whose career was outlined in the case report presented at the beginning of this article should be a huge warning sign that the future of medical dermatology as a specialty is uncertain. The Medical Dermatology Society hopes to develop a coalition with all other leadership organizations within dermatology to deal with this problem effectively. There is a need for a broader discussion within organized dermatology of the growing crisis in this area and how all dermatology leadership organizations working together can develop an action plan for effectively dealing with this important but challenging problem. Dermatology must ask itself what it wants to look like as a medical specialty in the future. Without an steady stream of young clinician-investigators focused on the many challenging problems in medical dermatology, dermatology will not exist as the specialty it is today.

Academic Medical Centers↗
PubMed2001

Papulosquamous disorders of the elderly.

Several papulosquamous skin conditions occur in the elderly, including inherited and acquired ichthyoses, psoriasis, cutaneous lymphoma, and cutaneous connective tissue diseases. The clinical presentations can be quite helpful in diagnosing these conditions, and confirmatory histology and immunologic testing can often better define the specific entities. Treatment often involves identifying underlying systemic causes, as well as specific approaches based on the diagnosis and severity of clinical presentation.

Aged↗
PubMed2000

Glucocorticoids induce a near-total suppression of hyaluronan synthase mRNA in dermal fibroblasts and in osteoblasts: a molecular mechanism contributing to organ atrophy.

Glucocorticoid (GC) administration induces atrophy of skin, bone, and other organs, partly by reducing tissue content of glycosaminoglycans, particularly hyaluronic acid (HA). We took advantage of the recent cloning of the three human hyaluronan synthase (HAS) enzymes (HAS1, HAS2 and HAS3), to explore the molecular mechanisms of this side effect. Northern and slot blots performed on RNA extracted from cultured dermal fibroblasts and the MG-63 osteoblast-like osteosarcoma cell line indicated that HAS2 is the predominant HAS mRNA in these cells. Incubation of both cell types for 24 h in the presence of 10(-6) M dexamethasone (DEX) resulted in a striking 97--98% suppression of HAS2 mRNA levels. Time-course studies in fibroblasts demonstrated suppression of HAS2 mRNA to 28% of control by 1 h, and to 1.2% of control by 2 h, after addition of DEX. Dose-response studies in fibroblasts indicated that the majority of the suppressive effect required concentrations characteristic of cell-surface GC receptors, a point confirmed by persistent DEX-induced suppression in the presence of RU486, an antagonist of classic cytosolic steroid hormone receptors. Nuclear run-off experiments showed a 70% suppression of HAS2 gene transcription in nuclei from DEX-treated fibroblasts, which is unlikely to fully explain the rapid 50--80-fold reduction in message levels. Experiments with actinomycin D (AMD) demonstrated that the message half-life was 25 min in cells without DEX, whereas the combination of AMD with DEX dramatically increased the half-life of HAS2 mRNA, suggesting that DEX acts by inducing a short-lived destabilizer of the HAS2 message. Direct assessment of HAS2 mRNA stability by wash-out of incorporated uridine label established a half-life of 31 min in cells without DEX, which substantially shortened in the presence of DEX. In conclusion, GCs induce a rapid and sustained, near-total suppression of HAS2 message levels, mediated through substantial decreases in both gene transcription and message stability. These effects may contribute to the loss of HA in GC-treated organs.

Atrophy↗
PubMed2000

Pemphigus vulgaris induced by D-penicillamine therapy in a patient with systemic sclerosis.

D: -Penicillamine-induced pemphigus occurs infrequently, typically in patients with rheumatoid arthritis. We describe a patient with systemic sclerosis who experienced this complication 3 months after starting D -penicillamine therapy. Nikolsky's sign, histopathologic findings, and direct immunofluorescence all confirmed the diagnosis. Termination of disease progression required intravenous pulse glucocorticoids, azathioprine, and 3 courses of plasmapheresis. The presentation, treatment, and etiology of D -penicillamine-induced pemphigus are reviewed, and the incidence of this complication in scleroderma patients is examined.

Aged↗
PubMed2000

Pulse glucocorticoids.

High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in a number of medical fields to avoid the complications and side effects of long-term glucocorticoid (GC) therapy and because of the perception that high-dose i.v. methylprednisolone may have "special" therapeutic effects. It is possible that aggressive early therapy with GCs allows for a more rapid taper of GCs and therefore prevents some of the dose-related side effects associated with long-term use. Some of the neurologic and rheumatologic literature related to multiple sclerosis and lupus nephritis suggest that i.v. methylprednisolone has therapeutic effects that are different from those of conventional doses of oral prednisone. There is still considerable debate about this in nondermatologic fields, and extrapolation of the role of pulse i.v. methylprednisolone to dermatologic disease, where trials are lacking, is difficult. Given this subset of possible candidates of this therapy as suggested by anecdotal reports, there is at least a rationale for considering the use of this modality in a subset of patients.

Clinical Trials as Topic↗
PubMed2000

Association of a promoter polymorphism of tumor necrosis factor-alpha with subacute cutaneous lupus erythematosus and distinct photoregulation of transcription.

Ultraviolet irradiation stimulates keratinocytes and dermal fibroblasts to release cytokines involved in apoptosis and immunomodulation, such as tumor necrosis factor-alpha and interleukin-1alpha. Recent work has associated the -308A polymorphism of the human tumor necrosis factor-alpha promoter with systemic lupus erythematosus and adverse outcomes in several infectious diseases. To explore the role of this polymorphism in ultraviolet-induced disease, we used two approaches. First, we examined its prevalence in individuals with different ultraviolet sensitivity. Compared with healthy controls, there was a substantially increased prevalence of -308A in subacute cutaneous lupus erythematosus, an extremely photosensitive form of cutaneous lupus erythematosus, but not in discoid lupus erythematosus, a less photosensitive form. Next, to examine molecular regulation by tumor necrosis factor -308A, cultured 3T3 fibroblasts were transiently transfected with chloramphenicol acetyl transferase reporter constructs under the control of either -308A or the wild-type -308G promoter. Without added interleukin-1alpha the two constructs produced similar baseline chloramphenicol acetyl transferase activity and similar responses to ultraviolet. The responses to interleukin-1alpha, a photoinduced cytokine, were markedly different: interleukin-1alpha without ultraviolet produced a 15-fold increase in chloramphenicol acetyl transferase transcription from the -308A construct without affecting the wild-type -308G. Interleukin-1alpha plus ultraviolet B caused a remarkable 300-fold increase in -308A chloramphenicol acetyl transferase transcription over baseline, while increasing the wild type to <15% of this level. These results indicate a clear difference between the two promoters, including a striking synergy between ultraviolet B and added interleukin-1alpha in the induction of transcription by the tumor necrosis factor-alpha -308A promoter. Overall, our findings indicate a strong linkage between the -308A polymorphism and subacute systemic lupus erythematosus, which is likely to directly contribute to the photosensitivity of these patients.

Chloramphenicol O-Acetyltransferase↗
PubMed2000

Annular erythema of Sjögren's syndrome in a white woman.

Annular erythema of Sjögren's syndrome (AE-SS) is believed to be the Asian counterpart of subacute cutaneous lupus erythematosus (SCLE) in white persons. We report the second case of a white person with AE-SS, diagnosed by clinical and serologic findings, as well as the absence of histologic criteria for SCLE. The diagnosis of AE-SS was established by symptoms of xerophthalmia and xerostomia, as well as by examination of skin and salivary gland biopsy specimens. Evaluation showed the presence of anti-Ro(SS-A) and anti-La(SS-B) autoantibody, with the presence of anti-Ro(SS-A) antibody against the 60-kd, but not the 52-kd, epitope, a pattern frequently seen in both the Asians with AE-SS and in white patients with SCLE. Both skin and sicca symptoms were alleviated with combination antimalarial therapy, which included hydroxychloroquine and quinacrine. This case demonstrates that AE-SS can occur in white patients and that the autoantibody profile is similar to that described in Asians with this disease.

Aged↗
PubMed2000

Leukocytoclastic vasculitis due to etanercept.

Recently etanercept, a soluble recombinant tumor necrosis factor receptor:Fc fusion protein, became available to treat patients with rheumatoid arthritis (RA). Among adverse reactions are cutaneous side effects, which occur in about 5% of patients. These have included mostly injection site reactions as well as urticarial reactions. We describe the first case of leukocytoclastic vasculitis associated with the use of etanercept in a patient with severe, deforming RA previously unresponsive to multiple therapies. Discontinuation of the drug led to complete resolution of the vasculitis.

Antirheumatic Agents↗
PubMed1999

Wavelength-specific synergy between ultraviolet radiation and interleukin-1 alpha in the regulation of matrix-related genes: mechanistic role for tumor necrosis factor-alpha.

Ultraviolet light causes both acute and chronic changes in extracellular matrix. We sought to examine the effects of different ultraviolet wavelengths on expression of matrix-related genes in fibroblasts. We previously reported that tropoelastin gene expression in vivo decreases with acute ultraviolet B exposure, and interleukin-1 alpha-mediated upregulation of tropoelastin is blocked in vitro after ultraviolet B radiation. In this study, we found that only ultraviolet B, but not ultraviolet A or ultraviolet A1, blocked the ability of interleukin-1 alpha to stimulate tropoelastin expression in vitro. Ultraviolet B and interleukin-1 alpha synergistically increased tumor necrosis factor-alpha secretion by fibroblasts, a finding not seen with ultraviolet B alone nor with ultraviolet A or ultraviolet A1 combined with interleukin-1 alpha. Keratinocytes showed a similar ultraviolet B-specific induction of tumor necrosis factor-alpha production. Addition of tumor necrosis factor-alpha to cultured fibroblasts blocked interleukin-1 alpha-induced stimulation of tropoelastin message, and addition of anti-tumor necrosis factor-alpha antibodies restored the responsiveness of tropoelastin and collagen messages to exogenous interleukin-1 alpha after ultraviolet B exposure. We conclude that interleukin-1 alpha in combination specifically with ultraviolet B induces fibroblasts to secrete tumor necrosis factor-alpha, and that this ultraviolet B-specific induction of tumor necrosis factor-alpha secretion is responsible for effects of ultraviolet B on the expression of matrix-related genes in the skin.

Cells, Cultured↗
PubMed1998

Lack of correlation of skin thickness with bone density in patients receiving chronic glucocorticoid.

The objective was to test the hypothesis that there is a correlation between thinning of the skin and bone in patients on chronic oral glucocorticoids (GCs). This was a one-time cross-sectional analysis performed in an academic referral center. The study group consisted of 14 patients on GCs for a variety of disorders, including dermatomyositis, pemphigus vulgaris, pyoderma gangrenosum, and urticarial vasculitis. Skin thickness was compared with that of 24 sex- and age-matched controls. The main outcome measures were the bone density of the lumbar spine (L2-L4) and the skin thickness. The skin thickness (mm, mean +/- SEM) in GC-treated (n = 7) vs unmedicated age-matched Caucasian women (n = 20) was 0.84 +/- 0.04 vs 1.02 +/- 0.04 (t = 3.07, P < 0.01) in the upper arm, 1.13 +/- 0.09 vs 1.49 +/- 0.05 (t = 3.65, P < 0.002) in the dorsal forearm, and 0.96 +/- 0.07 vs 1.17 +/- 0.02 (t = 2.92, P < 0.01) in the ventral forearm. L2-L4 bone densities averaged 106 +/- 2% in the GC-treated female patients relative to the age and sex-matched controls. There was no correlation between skin thickness and bone density. In GC-treated (n = 4) vs unmedicated Caucasian men matched for age (n = 4), skin thickness was 1.09 +/- 0.4 vs 1.33 +/- 0.05 (t = 3.51, P < 0.02) in the upper arm, but was not significantly different at the two forearm sites. No correlation between skin thickness and bone density was observed. The level of type I procollagen mRNA in skin from three GC-treated patients was 45% of the value in three age-matched controls. In conclusion, GCs cause statistically significant thinning of skin independently of the effects on bone.

Absorptiometry, Photon↗
PubMed1998

Thrombocytopenia after a single test dose of methotrexate.

Low dose methotrexate (MTX) can cause numerous gastrointestinal, pulmonary, central nervous system, and hematologic toxicities. Risk factors include folate deficiency, decreased renal function, older age, increased mean corpuscular volume or concomitant use of trimethoprim-sulphamethoxazole, probenecid, or nonsteroidal antiinflammatory drugs (NSAIDs). We describe a case of isolated thrombocytopenia after a single oral dose of MTX in a 36-year-old woman with sarcoidosis. She had rheumatoid arthritis and her only other medications included NSAIDs. One week after her first oral dose of 7.5 mg MTX, diffuse petechiae developed on her chest, abdomen, and extremities; she had a platelet count of 25,000/mm3. Nine days after discontinuation of both MTX and the NSAID, her platelet count increased to 189,000/mm3.

Adult↗
PubMed1997

Pathogenetic mechanisms and treatment of cutaneous lupus erythematosus.

The mechanisms of cutaneous lupus erythematosus are under active investigation, and important advances have been made. Humoral mechanisms are likely important in subacute cutaneous lupus erythematosus, the cutaneous subset most associated with the Ro antibody. Many advances have been made in understanding the various Ro epitopes and the specificities of the Ro antibody response. Lupus mice experiments have provided insight into the contributing roles of various T-cell subsets. Variations in cytokine production related to genetic polymorphisms and induction by ultraviolet light combined with alterations in selectins and adhesion molecules contribute to the accumulation of inflammatory cells in cutaneous lupus erythematosus. It is important to institute aggressive systemic therapy when there is widespread scarring disease. Antimalarial agents continue to be first-line systemic drugs, and our understanding of the use of combination antimalarial agents and proper dosing limits problems with toxicity and improves efficacy. Other therapies, including thalidomide, are helpful for patients with resistant disease.

Animals↗