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Biomedical subjects

K B Gordon

Publications and source records attributed to K B Gordon.

At least 19 recordsLinked to original sources
PubMed2005

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial.

BACKGROUND: Psoriasis is a chronic disease that significantly diminishes the health-related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor alpha monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. OBJECTIVES: The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. METHODS: In this double-blind, placebo-controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg(-1) of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. RESULTS: Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3- and 5-mg kg(-1) groups showed a median percentage improvement in DLQI scores of 84.0% and 91.0%, respectively, compared with 0% in the placebo group (P < 0.001). The median decrease from baseline in DLQI score at week 10 was 8.0 and 10.0 for the 3 and 5 mg kg(-1) infliximab groups, respectively, compared with 0 in the placebo group (P < 0.001). Thirty-three per cent and 40% of patients in the 3 and 5 mg kg(-1) infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0.001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0.61, P < 0.001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50-75% improvement in PASI during the same period (60%). CONCLUSIONS: Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.

Adult↗
PubMed2005

The tumour necrosis factor-alpha inhibitor adalimumab rapidly reverses the decrease in epidermal Langerhans cell density in psoriatic plaques.

BACKGROUND: The pathophysiology of psoriasis is poorly understood, and the mechanism of action of biological agents interfering with tumour necrosis factor (TNF)-alpha that improve psoriatic plaques is completely unknown. OBJECTIVES: To begin to unravel the mechanism of action, cellular changes occurring in plaques following administration of adalimumab, a humanized monoclonal antibody against TNF-alpha, were investigated. METHODS: Thirteen different patients underwent sequential biopsies as part of a clinical trial. Each biopsy was immunostained and evaluated to calculate the relative density of epidermal Langerhans cells (LCs) before and after treatment (days 2, 7, 28, 84). To explore the basis for reduced epidermal LC densities in plaques, a SCID-Hu animal model was utilized. Acute psoriatic lesions were created within 2 weeks by injection of superantigen-activated CD4+ T cells into engrafted symptomless skin. RESULTS: Compared with symptomless skin, untreated plaques had a significantly reduced density of epidermal LCs. There was a rapid increase in density of epidermal LCs in plaques following treatment with adalimumab beginning as early as day 7. The paucity of epidermal LCs in plaques was contrasted to the prominent density of LCs in other skin disorders with chronic inflammation and alterations in keratinization, including lichen planus and inflamed seborrhoeic keratosis. Rapid creation of plaques using the SCID-Hu model was accompanied by loss of epidermal LCs, indicating that diminished LC density occurs at an early stage of lesion formation. CONCLUSIONS: These data shed light on a new immunopathological perspective highlighting a rapid loss of epidermal LCs in acute psoriatic lesions, with sustained decreased density of LCs in chronic plaques. Furthermore, an unexpected insight into the mechanism of action was uncovered for adalimumab, in which rapid restoration of epidermal LC density was observed.

Adalimumab↗
PubMed2001

Ocular manifestations of leukemia: leukemic infiltration versus infectious process.

OBJECTIVE: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available. INTERVENTION: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs. MAIN OUTCOME MEASURES: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records. RESULTS: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection. CONCLUSIONS: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.

Adult↗
PubMed2001

Safety of the new macrolide immunomodulators.

With the wide acceptance of cyclosporine in the treatment of skin disease, there has been an effort to find new immunomodulating agents with superior safety profiles for use in dermatology. Among the most promising of the classes are the new macrolide immunomodulators, including tacrolimus and pimecrolimus. Of these, only tocrolimus has had widespread use for nondermatologic indications, primarily solid organ transplantation. Both of these agents have been studied for inflammatory diseases of the skin. In this article, we review the systemic and topical toxicities of these macrolide immunomodulators.

Humans↗
PubMed2000

Botulinum toxin type A for the treatment of axillary Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease is an inherited acantholytic disorder affecting the intertriginous areas of the body which is exacerbated by sweat, moisture, and friction. The disease is frequently resistant to conventional nonsurgical treatment. OBJECTIVE: To evaluate whether chemodenervation of sweat glands would improve the course of the disease in a patient with Hailey-Hailey. METHODS: We used low-dose treatment of the left axilla with botulinum toxin type A, the right axilla being used as a control, followed by treatment of both axillae with the optimal dose routinely used for the treatment of axillary hyperhidrosis. RESULTS: After one treatment with a low dose of botulinum toxin type A, we observed partial improvement of the treated axilla. With subsequent treatment of both axillae with the recommended dose for axillary hyperhidrosis, we observed a sustained complete remission of the disease in the treated axillae. CONCLUSION: Botulinum toxin type A may be an effective and safe nonsurgical alternative for the treatment of benign familial pemphigus in intertriginous areas such as the axillae.

Axilla↗
PubMed1999

In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model.

Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse interleukin-12 elevated tumoral and serum levels of interferon-gamma and tumor necrosis factor-alpha, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

Animals↗
PubMed1998

Presentation of proteolipid protein epitopes and B7-1-dependent activation of encephalitogenic T cells by IFN-gamma-activated SJL/J astrocytes.

There is controversy regarding the possible role of glial cells as APCs in the pathogenesis of central nervous system (CNS) demyelinating diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Microglia have been clearly shown to present Ag in the CNS, and due to the proximity of activated astroglial cells to infiltrating T cells and macrophages in demyelinating lesions, it is also possible that astrocytes positively or negatively regulate disease initiation and/or progression. We examined the capacity of IFN-gamma-treated astrocytes from EAE-susceptible SJL/J mice to process and present myelin epitopes. IFN-gamma activation up-regulated ICAM-1, VCAM-1, MHC class II, invariant chain, H2-M, CD40, and B7-1 as determined by FACS and/or RT-PCR analyses. B7-2 expression was only marginally enhanced on SJL/J astrocytes. Consistent with the expression of these accessory molecules, IFN-gamma-treated SJL/J astrocytes induced the B7-1-dependent activation of Th1 lines and lymph node T cells specific for the immunodominant encephalitogenic proteolipid protein (PLP) epitope (PLP139-151) as assessed by proliferation and activation for the adoptive transfer of EAE. Interestingly, IFN-gamma-activated astrocytes efficiently processed and presented PLP139-151, but not the subdominant PLP178-191, PLP56-70, or PLP104-117 epitopes, from intact PLP and a recombinant variant fusion protein of PLP (MP4). The data are consistent with the hypothesis that astrocytes in the proinflammatory CNS environment have the capability of activating CNS-infiltrating encephalitogenic T cells specific for immunodominant epitopes on various myelin proteins that may be involved in either the initial or the relapsing stages of EAE.

Adoptive Transfer↗
PubMed1998

Dermatologic manifestations of gastrointestinal disorders.

Many disorders of the gastrointestinal tract have cutaneous manifestations. Thus, a careful examination of the skin may uncover clues to underlying diseases of the liver, gastrointestinal tract, and pancreas. This article explores the alimentary-cutaneous relationship.

Digestive System Diseases↗
PubMed1998

Epitope spreading: lessons from autoimmune skin diseases.

Autoimmune diseases are initiated when patients develop aberrant T and/or B cell responses against self proteins. These responses presumably are directed to single immunogenic epitopes on these proteins. Recent data in animal models of autoimmune diseases suggest that the targets of immune responses in autoimmunity do not remain fixed, but can be extended to include other epitopes on the same protein or other proteins in the same tissue, a phenomenon termed "epitope spreading." The "epitope spreading" phenomenon also applies to situations in which tissue damage from a primary inflammatory process causes the release and exposure of a previously "sequestered" antigen, leading to a secondary autoimmune response against the newly released antigen. In experimental autoimmune animal diseases, "epitope spreading" seems to have significant physiologic importance in determining the course and duration of disease. In this paper, we review the current concepts in animal models of autoimmune diseases in order to define the "epitope spreading" phenomenon, and we then propose how this phenomenon might play a significant role in the development and the course of autoimmune skin diseases. Hopefully, an understanding of "epitope spreading" will help the dermatology community to better understand the pathogenesis of autoimmune skin diseases and to rationally fashion disease-specific immune therapy in the future.

Animals↗
PubMed1997

IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells.

Astrocytes may serve as effectual APCs for T cell-mediated immune responses to myelin components during multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Although astrocytes have been reported not to constitutively express MHC class II molecules, expression is up-regulated during active EAE and by in vitro incubation with IFN-gamma. Previous studies have reported that cytokine-activated astrocytes are able to activate Ag-specific previously activated T cells, but not naive alloreactive T cells. In the current study, we show that a subset of primary murine astrocytes constitutively expresses B7-2 molecules, as determined by FACS and PCR analyses, and up-regulates surface expression and mRNA levels of both B7-2 and B7-1 upon IFN-gamma stimulation. In contrast to earlier reports, we found that both untreated and IFN-gamma-treated astrocytes were able to stimulate proliferation of previously activated OVA-specific Th1 cells. In contrast, only IFN-gamma-treated astrocytes activated naive, transgenic OVA-specific T cells. Astrocyte-induced activation of both OVA-specific naive T cells and activated Th1 cells was dependent primarily on B7-2-mediated costimulation, as proliferation was inhibited by CTLA4-Ig and by anti-B7-2 mAbs. These results suggest that astrocytes in an inflammatory environment have the capacity to express the required MHC class II and B7 costimulatory molecules necessary for efficient activation of naive T cells. Since we have shown that T cells specific for endogenous myelin epitopes released during acute EAE play the major pathologic effector role in subsequent disease relapses (epitope spreading), astrocytes could play a role in the local activation and expansion of these responses.

Abatacept↗
PubMed1997

Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy.

Treatment of epidermolysis bullosa acquisita (EBA) with conventional therapy frequently does not result in improvement. Extracorporeal photochemotherapy (ECP) is a novel immunomodulating technique which might be of benefit in the treatment of autoimmune disease. We prospectively studied three patients with refractory EBA who were treated with ECP. All three patients had improvement in objective measurement of their disease severity while two of the three had significant subjective improvement in their skin fragility and the clinical activity of their disease. Both the objective and subjective manifestations of the disease continued to improve 6 months after completion of the protocol. ECP may be therapeutic option in the treatment of patients with EBA who are refractory to conventional therapy.

Aged↗
PubMed1996

The cutaneous manifestations of gastrointestinal disease.

Specific cutaneous manifestations are found to be associated with gastrointestinal disease. A careful examination of the skin, therefore, may uncover clues to underlying diseases of the gastrointestinal tract, pancreas, and liver. This article explores the alimentary cutaneous relationship.

Adenomatous Polyposis Coli↗
PubMed1996

Bowen's disease of the distal digit. Outcome of treatment with carbon dioxide laser vaporization.

BACKGROUND: Bowen's disease (squamous cell carcinoma in situ) is an intraepithelial neoplasm that can transform into invasive squamous cell carcinoma. The preferred method of eradication for Bowen's disease is surgical excision. However, when Bowen's disease occurs on the digit, surgical removal can lead to scar contracture and loss of use of the finger. OBJECTIVE: To assess the utility of carbon dioxide (CO2) laser vaporization in eradicating Bowen's disease of the finger while maintaining the full range of motion and use of the digit. METHODS: Five patients were treated with CO2 laser vaporization for Bowen's disease of the digit. Patients were followed postoperatively for recurrence, clinical appearance, especially for scar formation, and function of the involved joints over a 6-month to 3-year period. RESULTS: Four of five patients had no recurrence. Healing resulted in only modest alterations in the cosmetic appearance in comparison with the surrounding untreated skin. Posttreatment biopsy showed slight thinning of the epidermis and mild fibroplagia limited to the papillary dermis. Patients reported only mild post-procedure discomfort and no patients had any loss of function of the digit. CONCLUSIONS: CO2 laser vaporization may be a safe and effective means by which to eradicate Bowen's disease of the finger without the risk of scar contracture and loss of function of the digit.

Adult↗
PubMed1995

Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) is a common complication of patients infected with human immunodeficiency virus and can cause significant morbidity. Long term therapy with standard chemotherapeutic regimens has been limited by relatively short durations of response and potential toxicity. Once therapy is discontinued, the disease typically progresses. Liposome-encapsulated doxorubicin (DOX-SL) currently is being evaluated for treating patients with AIDS-related KS. Early reports suggest a high response rate and good patient tolerance permitting continued therapy for extended periods. METHODS: Patients with AIDS-related KS are treated with a DOX-SL regimen every 2-3 weeks and are followed carefully for evidence of adverse treatment effects. RESULTS: Two cases of hand-foot syndrome (HFS) in patients receiving DOX-SL for AIDS-related KS are reported. Tissue studies demonstrated changes consistent with a toxic effect of the drug on keratinocytes. Hand-foot syndrome was reversible once treatment stopped; however, treatment cessation resulted in primary disease recurrence. CONCLUSIONS: Hand-foot syndrome can be debilitating and may be a limiting factor in the prolonged use of DOX-SL for AIDS-related KS for some patients. It is critical for clinicians using this drug to identify this side effect to limit HFS-associated morbidity.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Late effects of radiation on the eye and ocular adnexa.

A clinically useful classification system is suggested that can be used in prospective trials to evaluate the effects of radiation on the visual system. We review radiation-induced pathophysiological and clinical changes of the various ocular structures as well as dose-response data and management of ocular complications. The rationale for the classification scheme chosen is also discussed.

Cataract↗