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Biomedical subjects

J Yeager

Publications and source records attributed to J Yeager.

At least 19 recordsLinked to original sources
PubMed2003

The efficacy and safety of a topical alprostadil cream, Alprox-TD, for the treatment of erectile dysfunction: two phase 2 studies in mild-to-moderate and severe ED.

In two multicenter, placebo controlled, phase 2 studies, patients with mild-to-moderate (n=161, Study 1) or severe (n=142, Study 2) erectile dysfunction (ED) were randomized to receive placebo, 0.05, 0.1, or 0.2 mg (Study 1) or placebo, 0.1, 0.2, or 0.3 mg (Study 2) of topically applied alprostadil (containing a proprietary skin permeation enhancer). The primary efficacy end point in both studies was the change in erectile function (EF) score from baseline to final visit. The changes from baseline for EF scores were -0.8+/-1.1, 1.8+/-1.1, 0.7+/-1.2, and 3.7+/-1.2 (P<0.01; Study 1) and 2.7+/-1.3, 6.29+/-1.4, 6.49+/-1.5, and 9.44+/-1.5 (P<0.001; Study 2) for ascending dose groups in each study. Topical alprostadil was well tolerated with the most common adverse event being urogenital pain. These results suggest this topical alprostadil formulation may be a potentially useful agent for the treatment of ED.

Administration, Topical↗
PubMed2002

Cholesterol embolization syndrome: cutaneous histopathological features and the variable onset of symptoms in patients with different risk factors.

Cholesterol embolization syndrome (CES) may not only be due to direct dislodgement of cholesterol crystals from atherosclerotic plaques on the walls of arteries by surgery, angiogram or trauma, but may occur after anticoagulant and thrombolytic therapy. The latter two therapies both weaken the fibrin clot that stabilizes the atheromas in place; however, these two therapies commonly have different onsets of CES after their institution. We present three patients with different risk factors for CES who all presented with the pathognomonic triad of leg and/or foot pain, livedo reticularis and good peripheral pulses. In all three patients cholesterol emboli were demonstrated in cutaneous biopsy sections. In two patients there was associated renal involvement, which was fatal in one case. These cases illustrate that cutaneous biopsy may be diagnostic in patients with livedo reticularis, which progresses to necrosis and gangrene. In addition, they illustrate the problems and contradictions involved in treating patients with CES.

Aged↗
PubMed2001

Pseudocyst of the auricle: diagnosis and management with a punch biopsy.

A case of pseudocyst of the ear diagnosed and treated with a punch biopsy is reported. Pseudocyst of the ear is considered to be a benign, asymptomatic condition seen infrequently in clinical practice. Our patient is a 45-year-old white man who presented with a 5-month history of a painless nodule on his left auricle without any preceding history of trauma. Although many treatments have been reported, none appear satisfactory, and many surgical treatment modalities are cumbersome. This is the first report, to our knowledge, of a case of a pseudocyst of the ear confirmed and treated with a 3-mm punch biopsy of the inferior border of the pseudocyst, followed by a pressure bolster.

Biopsy↗
PubMed2000

Fixed drug eruptions to human immunodeficiency virus-1 protease inhibitor.

Despite numerous drug interactions that occur with human immunodeficiency virus-1 protease inhibitors, there are relatively few drug reactions. We present two patients receiving saquinavir who developed fixed drug reactions. Both reactions cleared while patients received a therapeutic dose of the medication, and in one patient a flare was seen when the patient later stopped and then restarted the medication. Although fixed drug reactions are relatively inconsequential, it is important to know that these eruptions may clear when the patient is given uninterrupted therapy of a human immunodeficiency virus-1 protease inhibitor, with only post-inflammatory hyperpigmentation.

Adult↗
PubMed1999

Micrococcus folliculitis in HIV-1 disease.

Organisms with little pathogenic potential in immunocompetent hosts may produce disease in HIV-1 + patients. We describe three HIV-1 + patients in late disease who presented with pruritic papules with central ulceration over the face and arms. In all the patients the eruptions had been present for months, and the patients did not develop sepsis. Biopsy specimens in all the patients showed large Gram-positive cocci, forming tetrads. Colony morphology, catalase positivity and coagulase negativity, and resistance to nitrofurantoin were used to separate micrococci from staphylococci. Micrococcus species are usually considered normal inhabitants of the skin; however, in patients with HIV-1 disease, Micrococcus species can produce localized cutaneous infections.

Adult↗
PubMed1999

The effect of decreasing digital image resolution on teledermatology diagnosis.

OBJECTIVE: To determine the effect of degraded digital image resolution (as viewed on a monitor) on the accuracy and confidence of dermatologic interpretation. MATERIALS AND METHODS: Eight dermatologists interpreted 180 clinical cases divided into three Logical Competitor Sets (LCS) (pigmented lesions, non-pigmented lesions, and inflammatory dermatoses). Each case was digitized at three different resolutions. The images were randomized and divided into (9) 60-image sessions. The physicians were completely blinded concerning the image resolution. After 60 seconds per image, the viewer recorded a diagnosis and level of confidence. The resultant ROC curves compared the effect of LCS, level of clinical difficulty, and resolution of the digital image. One-way analysis of variance (ANOVA) compared the curves. RESULTS: The areas beneath the ROC curves did not demonstrate any consistently significant difference between the digital image resolutions for all LCS and levels of difficulty. The only significant effect observed was amongst pigmented lesions (LCS-A) where the ROC curve area was significantly smaller in the easy images at high resolution compared to low and medium resolutions. For all other ROC curve comparisons within LCS-A, at all other levels of difficulty, as well as within the other LCS at all levels of difficulty, none of the differences was significant. CONCLUSION: A 720 x 500 pixel image can be considered equivalent to a 1490 x 1000 pixel image for most store-and-forward teledermatology consultations.

Analysis of Variance↗
PubMed1999

Increased soft tissue in the posterior cervical and upper back area of patients on HIV-1 protease inhibitors.

BACKGROUND: Corticosteroids as well as sex hormones affect the redistribution of subcutaneous fat and the percentage of lean body mass. In addition, some stromal cells express steroid receptors, and the quantity and distribution of these receptors vary at different body sites and between sexes. Inhibitors of HIV-1 protease may affect steroid hormone metabolism through their effect on cytochrome P450. OBJECTIVES: To determine the changes in the tissue of the back in three HIV-1+ patients who developed increased soft tissue in posterior cervical and upper back areas while on HIV-1 protease inhibitors. METHODS: Punch biopsies of the involved posterior cervical and upper back areas were done. These included subcutaneous adipose tissue. Routine hematoxylin and eosin-stained sections, along with special stains for elastic and stromal mucin, and immunohistochemical stains for CD34 (HPCA-1 and Factor XIIIa) were evaluated. RESULTS: Histologically all three patients showed identical features. There was expansion of the dermis with decreased periadnexal fat and marked widening of the fibrous septa within the expanded subcutaneous fat. CONCLUSIONS: The posterior cervical and upper back area appears to be a common site for localization of mesenchymal tumours that show some fat differentiation and produce an increase in stromal matrix material. Mesenchymal cell populations within this area are also affected by systemic diseases. A male predominance pattern occurs with these conditions, and steroid receptors are expressed on some mesenchymal cells, that vary with the body location. Thus, this observation may be related to the effects of protease inhibitors on steroid hormone metabolism through their inhibition of cytochrome P-450.

Adipose Tissue↗
PubMed1998

Is CD30 (Ki-1) immunostaining in cutaneous eruptions useful as a marker of Th1 to Th2 cytokine switching and/or as a marker of advanced HIV-1 disease?

CD30 is a member of the tumour necrosis factor/nerve growth factor receptor superfamily, which is expressed on CD4+ and CD8+ T-cell clones which produce T helper (Th) 2-type cytokines. It has been proposed that disease progression in HIV-1 is associated with Th1 to Th2 cytokine switching. In 70 cutaneous biopsies from HIV-1 positive patients in different stages of disease, we performed a battery of immunohistochemical stains. These included antibodies to CD3, UCHL-1, OPD-4, L-26, KP-1 and CD30 (Ki-1). In addition, we used a similar battery of stains on cutaneous biopsies of HIV-1 negative patients with inflammatory dermatoses which are established as Th1 or Th2 dominant, e.g. polar leprosy. CD30+ cells were rarely present in early stages of HIV-1 disease, but commonly present in later stages of disease. However, there were cases of late HIV-1 disease which did not contain CD30+ cells. Increased numbers of CD30+ cells were more commonly seen in later stages of HIV-1 disease. However, the expression of CD30 appeared to be better in predicting other established Th2 cutaneous infiltrates in HIV-1 negative patients than in predicting a Th2 cutaneous cytokine pattern in advanced HIV-1 disease.

Biomarkers↗
PubMed1998

Lymphoid markers, activation markers, and adhesion molecules in cutaneous biopsy specimens from HIV+ patients with disease progression. The Military Medical Consortium for the Advancement of Retroviral Research.

BACKGROUND: One important factor in understanding the pathogenesis of human immune deficiency virus (HIV) disease is documenting the patterns of immune dysregulation present in HIV-positive patients. The cells which home to skin are mainly certain subsets of T cells and, as opposed to the peripheral blood, where circulating factors may inhibit terminal phenotypic differentiation, the cutaneous environment potentiates differentiation during cutaneous eruptions. OBJECTIVE: The authors' aim was to characterize the inflammatory dermatoses in biopsy specimens from HIV-positive patients with immunohistochemical stains for lymphoid markers, activation markers, and adhesion molecules and to determine if there was any correlation with the type of dermatosis and the HIV-disease stage. METHODS: Lymphoid and activation markers as well as adhesion molecules were studied on cutaneous biopsy specimens from 96 inflammatory dermatoses in HIV-positive patients. The dermatoses included psoriasiform dermatoses with and without a lichenoid component, perivascular lymphoid dermatoses, perivascular and periadnexal inflammatory dermatoses, spongiotic dermatoses, granulomatous dermatoses, and neutrophilic dermatoses with and without vasculitis. RESULTS: Although there was a decrease in CD4/CD8 ratios in the cutaneous inflammatory dermatoses with progression of the disease, the ratios of CD4/CD8 cells were far higher than those in the peripheral blood. There were also increasing numbers of CD23+ cells and increased E-Selectin expression on endothelial cells from the early stages of disease, with no consistent pattern of ICAM-1 expression on epithelial cells with disease progression. CONCLUSIONS: The expression of lymphoid markers, activation markers, and adhesion molecules in the skin with progression of HIV disease, is consistent with a T helper (Th)1 to Th0/Th2 cytokine pattern of immune dysregulation. This cytokine pattern may be modified by the cytopathic effects of HIV on lymphoid and dendritic populations and by effects of other concurrent infections. Significant numbers of CD4+ T cells in skin infiltrates, with low peripheral CD4 T-cell counts, suggest that the cutaneous T-cell populations may be distinctive.

Antigens, CD↗
PubMed1997

Pityriasis lichenoides et varioliformis acuta in HIV-1+ patients: a marker of early stage disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

BACKGROUND: The high incidence of cutaneous disease in HIV-1+ patients may be a marker of the chronic state of immune activation. In addition, specific cutaneous diseases may be related to the pattern and degree of immune dysregulation present in the patients at the time of the eruption. We have observed that HIV-1+ patients with pityriasis lichenoides et varioliformis acuta (PLEVA) were in the early to midstage of HIV-1 disease. MATERIALS AND METHODS: To determine if there was a correlation between the phenotype of the lymphoid infiltrate and surface markers of the epidermis and the known changes in early or late-stage HIV-1 disease, we studied five HIV-1+ patients with PLEVA. Cutaneous biopsy specimens were obtained and immunohistochemical stains were used to determine the expression of ELAM-1, ICAM-1, and HLA-DR and the phenotype of the lymphoid infiltrate. RESULTS: The HIV-1+ patients showed increased expression of HLA-DR on keratinocytes as well as on the mononuclear and dendritic cell populations in the epidermis and dermis. The majority of T cells were activated CD8+ cells. CONCLUSIONS: Immunophenotyping of the inflammatory infiltrate in these patients is consistent with a pattern of immune dysregulation seen only in earlier stages of HIV-1 disease. Thus, PLEVA may be useful as a marker of early to midstages of HIV-1 disease.

Adult↗
PubMed1997

Increased cutaneous toxicity to ionizing radiation in HIV-positive patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

BACKGROUND: There are reports of increased reactions in HIV-1+ patients to ultraviolet light sometimes in association with medication. In addition, there are also reports of increased morbidity associated with radiation therapy in HIV-1+ patients. METHODS: Three HIV-1+ patients developed cutaneous toxic reactions to radiation therapy; two with Kaposi's sarcoma (KS) and one with non-Hodgkin's lymphoma. CONCLUSIONS: Although the mechanisms which resulted in these reactions are not clear, they may be related to depletion of endogenous scavengers and may be accentuated by the pattern of immune dysregulation present in HIV-1 disease.

Adult↗
PubMed1997

Histopathologic features seen in cutaneous photoeruptions in HIV-positive patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

BACKGROUND: There have been scattered reports of HIV+ patients with increased reactions to light as well as anecdotal reports of HIV+ patients with increased morbidity secondary to radiation therapy. METHODS: As a part of a military study of HIV+ patients, we followed 987 patients for cutaneous disease for 4 years. All patients were questioned on a periodic basis about increased sensitivity to light. These patients received a physical examination at each protocol visit, and they were given the opportunity to receive all their dermatologic care within the HIV clinic. Fourteen of the patients with photo-induced eruptions were evaluated clinically at the time of the eruption, and 11 of these were biopsied. RESULTS: Thirty-three of the patients reported photo-induced reactions unrelated to oral medications. Although sensitivity to light often began in the early stages of HIV disease, reactions became more severe and more chronic with disease progression. Histologic features varied from few to numerous apoptotic/necrotic keratinocytes within the mid to upper levels of the epidermis associated with a perivascular inflammatory infiltrate, to apoptotic/necrotic keratinocytes throughout an acanthotic epidermis with a lichenoid/interface infiltrate. CONCLUSIONS: Although the pathogenesis of these light reactions is not known, these reactions may be related to depletion of endogenous scavengers which results in increased oxidative stress and is modulated by the pattern of immune dysregulation and metabolic dysregulation induced by HIV disease.

Acantholysis↗
PubMed1997

Histologically distinctive papular neutrophilic xanthomas in HIV-1 + patients.

Xanthomas may be associated with benign or malignant lymphoproliferative diseases, often with associated hypergammaglobulinema. In human immunodeficiency virus type 1 (HIV-1) disease, there is a high lymphoproliferative rate despite the immunodeficiency and increased cell death. We report three HIV-1-positive patients with facial papular xanthomatosis eruptions associated with hypergammaglobulinema, and an immunoglobulin A (IgA) gammopathy. Histopathologic features include lipid-laden macrophages, extracellular nuclear dust with phagocytosized nuclear debris, and hyalinization with areas of hyaline necrosis of collagen fibers. These distinctive papular xanthomas may be a marker of HIV-1 disease and of a pattern of immunodysregulation, immunodeficiency, and lymphoid proliferation seen in HIV-1 disease.

Adult↗
PubMed1997

Pruritus in HIV-1 disease: therapy with drugs which may modulate the pattern of immune dysregulation.

BACKGROUND: Pruritus in HIV-1+ patients is common and increases with disease progression. The causes of pruritus are numerous including xerosis, drug and photoeruptions, follicular and papular eruptions as well as infestations and infections by a wide range of organisms. One other possible factor contributing to pruritus is the pattern of immune dysregulation. With advancing HIV-1 disease there is Th1 to Th2 cytokine switching. METHODS: After some positive results with prostaglandin inhibitors, we undertook a study in which we randomly placed patients on four different forms of therapy for their pruritus. The therapies included hydroxyzine with or without doxepin at night, pentoxifylline, indomethacin and topical moisturization with medium-strength topical steroids. All patients were evaluated for both subjective relief as well as side effects. RESULTS: Patients placed on indomethacin obtained relief more consistently and more completely. Patients on pentoxifylline had the fewest side effects of all oral therapies. Patients on antihistamines with or without doxepin had the highest incidence of side effects, although more of these patients reported a greater degree of relief than patients on pentoxifylline. All patients on oral therapy overall had greater relief than patients using topical steroids. CONCLUSION: The systemic therapies which may modulate the pattern of immune dysregulation seen in HIV-1 disease may be beneficial in the pruritus seen in late-stage patients.

Administration, Cutaneous↗
PubMed1997

Increased drug reactions in HIV-1-positive patients: a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

Drug reactions are common in HIV-1 disease, with the incidence having been reported to increase with increasing stage and with CD4+ T-cell counts below 200/microliters. However, there have been numerous reports of patients in which rechallenge, dosing changes or continued therapy have resulted in no recurrence or else clearing of the eruption. We followed 974 HIV-1-positive patients for 46 months as a part of a military study of HIV-1 disease. Within this group there were a total of 283 drug eruptions, with cutaneous manifestations in 201 patients in which clinical characteristics were noted and 86 patients in which cutaneous biopsies were performed. Serological evidence of reactivation or acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections were also noted, as well as peripheral eosinophilia. The incidence of drug eruptions significantly increased with increasing Walter Reed stage and decreasing CD4 counts and CD4/CD8 ratio, as well as with increasing age and in patients with increased numbers of other dermatological diagnoses. In addition, white patients had significantly more drug eruptions than did black. Serological or culture evidence of acute or reactivated EBV or CMV was significantly increased in patients with drug eruptions. The majority of the eruptions were maculopapular or morbilliform with a predominantly perivascular mononuclear cell infiltrate. HIV-1 positive patients have an increased incidence of drug reactions, the incidence having been reported to increase in patients with less than 200 CD4+ T cells/microliter. However, at very low T4 counts, especially those less than 25/microliter, and at a CD4/CD8 ratio of less than 0.10, the probability of reactions to trimethoprim-sulphamethoxazole (TMP-SMZ) is decreased in late-stage HIV-1 patients. Maculopapular or morbilliform eruptions are the most common clinical presentations, often accompanied by one or more of the following: fever, arthralgias, eosinophilia, and serum transaminase elevation. Histologically the majority of these eruptions show a perivascular mononuclear cell infiltrate, sometimes with focal interface changes and apoptotic, necrotic cells within the epidermis. Acute hypersensitivity reactions and toxic epidermal necrolysis (TEN) or Stevens-Johnson's syndrome (SJS) with diffuse epidermal apoptosis and necrosis have also been less commonly described. In a study of cutaneous manifestations in an HIV-1 positive military population, drug reactions were evaluated in terms of clinical features, histopathology, demographic features and laboratory findings.

Adolescent↗