Biomedical subjects

H Skelton

Publications and source records attributed to H Skelton.

At least 19 recordsLinked to original sources

PubMed2006

A procedure for image enhancement in chromosome painting.

An image enhancement procedure was developed to produce high-contrast chromosome paint images. This procedure is well suited for images where brightness-contrast enhancement is subjective. Three examples are given to show that the procedure is very efficient to remove non-specific hybridization signals from the chromosome paint image. Chromosomes of roe deer contain large amounts of centromeric heterochromatic DNA. Echidna chromosomes show specific heterochromatic DNA distributed over several chromosomes. In both cases chromosome identification was hampered by bright heterochromatic regions. The enhancement tool was fully used in cross-species chromosome painting, which is the last example. The three examples show that the procedure is very simple to use and removes background in a controlled and defined manner.

Animals↗

PubMed2004

Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern.

Imidazoquinolines are topical immune response modifiers. Imiquimod (IMI), the first imidazoquinoline, is approved for the treatment of genital human papillomavirus disease and has shown success as a therapeutic agent for cutaneous premalignant and malignant tumours. To define the pattern of polarization of the local immune response to invasive cutaneous squamous cell carcinoma (SCC) we pretreated 10 SCCs that were > 3 cm in diameter for 2 weeks with IMI. The tumours were treated on Monday, Wednesday and Friday and excised the next Monday. A battery of immunohistochemical markers was used to define the mononuclear cell populations in the diagnostic, and the excisional biopsy specimens. The total inflammatory infiltrate was increased after IMI therapy: the greatest increase was in the CD8 T cells with a marked relative decrease in the CD68 monocytic/macrophages; the majority of the CD8 T cells showed expression of cytotoxic granules, T cell-restricted intracellular antigen (TIA) and granzyme B. The relative numbers of monocytes/macrophages were decreased after therapy with IMI with a decrease in CD68+, CD23+, and CD14+ cells and an increase in MAC-397+, and factor XIIIa+ cells. The epidermal dendritic cells showed a > 75% decrease in CD1a+ cells. The immunohistochemical marker profile after IMI therapy is consistent with that induced by a Th1 and M1 cytokine polarization pattern. This cytokine pattern is known to be more effective in defence against tumours as well as viral infections.

Administration, Topical↗

PubMed2002

Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E.

Histologically, granuloma annulare (GA) is a common non-infectious necrobiotic granulomatous reaction pattern that correlates with a number of different, but relatively specific clinical presentations. The cause or causes of GA are unknown: when localized, it is usually self-limiting, but it may be persistent when disseminated. We present three women who had had disseminated GA for more than 1 year. One patient had previously been treated with isotretinoin with no response. All three patients were treated with vitamin E 400 IU daily and zileuton 2400 mg daily. All responded within 3 months with complete clinical clearing. The anti-inflammatory and immune regulatory effects of vitamin E and zileuton may be an effective treatment in some patients with prolonged disseminated/generalized GA.

Drug Therapy, Combination↗

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

Peroxisomes in dermatology. Part II.

BACKGROUND: Peroxisomes are small cellular organelles that were almost ignored for years because they were believed to play only a minor role in cellular functions. However, it is now known that peroxisomes play an important role in regulating cellular proliferation and differentiation as well as in the modulation of inflammatory mediators. In addition, peroxisomes have broad effects on the metabolism of lipids, hormones, and xenobiotics. Through their effects on lipid metabolism, peroxisomes also affect cellular membranes and adipocyte formation, as well as insulin sensitivity, and peroxisomes play a role in aging and tumorigenesis through their effects on oxidative stress. OBJECTIVE: To review genetically determined peroxisomal disorders, especially those that particularly affect the skin, and some recent information on the specific genetic defects that lead to some of these disorders. In addition, we present some of the emerging knowledge of peroxisomal proliferator activator receptors (PPARs) and how ligands for these receptors modulate different peroxisomal functions. We also present information on how the discovery of PPARs, and the broad and diverse group of ligands that activate these members of the superfamily of nuclear binding transcription factors, has led to development of new drugs that modulate the function of peroxisomes. CONCLUSION: PPAR expression and ligand modulation within the skin have shown potential uses for these ligands in a number of inflammatory cutaneous disorders, including acne vulgaris, cutaneous disorders with barrier dysfunction, cutaneous effects of aging, and poor wound healing associated with altered signal transduction, as well as for side effects induced by the metabolic dysregulation of other drugs.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Peroxisomes in dermatology. Part I.

Aging↗

PubMed2001

CD34-positive cellular blue nevi.

BACKGROUND: Although cellular blue nevi (CBN) are well known and characterized, the histopathologic and clinical spectrum of these tumors continues to evolve. We report four CBN with a distinctive histologic and immunohistochemical pattern. METHODS: The histologic features and immunohistochemical staining for S-100 protein, HMB-45, Bcl-2 and CD34 of four CBN with distinctive features were evaluated using routine methods and compared to common CBN. RESULTS: All four of these distinctive CBN where known to be congenital, and all showed aggregates of plump spindled cells with round to oval nuclei in aggregates and more slender spindled cells with thin wavy nuclei. The slender, spindled cells showed an infiltrative pattern laterally into the dermis and deep into the subcutaneous fat. All four tumors showed diffuse expression of an immunohistochemical stain for CD34, as well as for S-100 protein, Bcl-2, and HMB-45. CONCLUSION: Positive immunohistochemical staining with the progenitor marker CD34 defines a subset of CBN. These tumors appear to fit within the spectrum of neurocristic cutaneous hamartomas and may arise from more primitive neurocristically derived cells. Further follow-up of these tumors will be necessary to determine whether this subset of CBN defines a subset with a characteristic biologic behavior.

Adolescent↗

PubMed2001

Metastatic adenocarcinoma of the esophagus to the skin: new patterns of tumor recurrence and alternate treatments for palliation.

BACKGROUND: Esophageal cancer, particularly adenocarcinoma of the esophagus (ACE), has been steadily increasing in incidence in the United States. In the past, patients usually died rapidly with locoregional disease that leads to inanition and aspiration. However, today when patients with ACE are treated successfully with induction chemotherapy and radiation therapy, followed by surgical excision, ACE usually does not recur locally, but presents with metatastic disease. We present a 62-year-old white male with ACE, which was treated with induction chemotherapy and radiation therapy followed by surgical excision. After approximately 1 year with no evidence of locoregional recurrence, the patient presented with diffuse cutaneous metastatic disease. METHODS: In addition to routine staining immunohistochemical stains for CK(AE1/AE3), CK7, CK 20, EMA, alpha-smooth muscle (SM) actin, S-100 protein, CD34, P53, Bcl-2, c-erbB-2 were performed. RESULTS: The immunohistochemical profile was consistent with an esophageal origin showing positive staining with CK20 and CK7 as well as AE1/AE3 and EMA. In addition, there was marked nuclear expression of p53, as well as membrane expression of c-erb-B2; consistent with progression of the disease and poor response to further cytotoxic therapeutic regimes. CONCLUSIONS: With new therapeutic protocols, we can expect to see more metastatic disease with recurrences of ACE. The histopathologic features and the immunohistochemical profile of the recurrent tumors may be helpful in determining alternate forms of therapy that either alone or in combination could be useful in palliation and delaying progression.

Adenocarcinoma↗

PubMed2001

Common variable immunodeficiency treated with a recombinant human IgG, tumour necrosis factor-alpha receptor fusion protein.

Common variable immunodeficiency (CVI) is characterized by a failure in B-cell differentiation and impaired immunoglobulin secretion, but with a variable clinical presentation, including the development of sarcoidal granulomas and autoimmune diseases, as well as an increased incidence of malignancies. We present a 21-year-old white man who carried a diagnosis of juvenile rheumatoid arthritis and presented 6 years later with scarring alopecia showing sarcoidal granulomas. Further work confirmed the diagnosis of CVI, and with increasing systemic symptoms, it was elected to treat the patient with a tumour necrosis factor (TNF)-alpha antagonist, a TNF-alpha receptor IgG1 fusion protein. The patient showed improvement in his systemic symptoms and some hair regrowth after 3 months of therapy, and continued improvement in his systemic disease with only mild scalp hair thinning in the areas of prior involvement after almost 1 year of therapy. CVI and sarcoid may have overlapping clinical and immunological findings. Previous therapies for CVI, including intravenous immunoglobulin, have not altered the mortality of the disease. TNF-alpha is a primary cytokine and is elevated in CVI, and specific inhibition of TNF-alpha in this patient was effective in moderating his disease, including his skin disease.

Adult↗

PubMed2001

Trichophyton rubrum showing deep dermal invasion directly from the epidermis in immunosuppressed patients.

Trichophyton rubrum is the most widely encountered dermatophyte infection, and is usually regarded as exclusively keratinophilic often leading to chronic cutaneous and nail infections, even in healthy individuals. We present three patients with acute leukaemias, with ill-defined pre-existent cutaneous eruptions that were treated with a potent topical corticosteroid. All three patients received aggressive marrow toxic chemotherapy. These patients had progression of their cutaneous disease, which showed deep dermal invasion of T. rubrum, invading directly from the epidermis with no evidence of systemic spread. We conclude that systemic pancytopenia, in association with prolonged local immunosuppression, may increase the risk of direct dermal invasion of dermatophyte infections. However, even in these patients, the risk of systemic spread still appears very low. Amphotericin B did not appear effective in treating these dermatophyte infections.

Adolescent↗

PubMed2001

Neonatal lupus erythematosus: factors which may lead to clinical disease in the foetus even in the absence of disease in the mother.

Neonatal lupus erythematosus (NLE) occurs in neonates of mothers who, in almost all cases, have auto-antibodies to the SSA/Ro associated proteins, but who may have no clinical disease. However, only a small percentage of mothers with SSA/Ro antibodies have affected babies, predisposing factors specific to the foetus or neonate (i.e. HLA pattern) and/or fetal maternal interactions have been proposed to be important. We present a mother with a family history of autoimmune disease, but without clinical disease, whose baby developed cutaneous NLE. Autoantibody determinations as well as the HLA-DR/DQ were performed in the mother and baby. Factors other than the HLA-DR/DQ status of the mother appear to be important in determining whether or not the neonate will develop NLE. Auto-antibodies to endogenous antigens common to the mother, transiently expressed developmental antigens, and the isotype specificity of transferred antibodies may be important in determining disease in the baby.

Adult↗

PubMed2001

Histologic features seen in changing nevi after therapy with an 810 nm pulsed diode laser for hair removal in patients with dysplastic nevi.

BACKGROUND: The majority of lasers used for hair removal target melanin as the chromophore. In contrast with other cutaneous applications of lasers, lasers used for hair removal must generate a limited, controlled degree of thermal damage to permanently remove hairs. AIM: To remove excess back hair from two male patients, one with a history of multiple nevi, and prior biopsies showing features of dysplastic nevi, and the other with large nevi greater than 6 mm in diameter and a family history of malignant melanoma. METHODS: Both patients received monthly treatments with an 810 nm, pulsed, high-power diode laser using a fluence of 20 J/cm2 and 25-30 J/cm2, respectively, and a pulse duration of 30 ms. RESULTS: Both patients presented 1 month after their last treatment with changing nevi within the treatment areas. Neither patient had clinical inflammation or other alterations suggestive of change in the nevi related to treatment. Thus, the nevi were excised with no mention of the previous laser treatment. The histologic features in all nevi were similar. There was subepidermal blister formation with elongation and disruption of nevus cells. There was homogenization of the collagen within the papillary dermis in all lesions. Only small foci of nevus cells could be identified in the dermis in some of the biopsy specimens. In these biopsy specimens, the dermal stromal matrix homogenization extended into the reticular dermis. CONCLUSIONS: Laser targeting of nevus cells and surrounding structures may produce clinically atypical nevi in areas previously treated for hair removal. This should be kept in mind, especially in patients with a history of dysplastic nevi or with a personal or family history of malignant melanoma.

Adult↗

PubMed2001

Squamous cell carcinoma in situ (Bowen's disease) in renal transplant patients treated with 5% imiquimod and 5% 5-fluorouracil therapy.

BACKGROUND: Depending upon the patient's age at transplant, skin type, sun exposure, and the need for immunosuppressive therapy to prevent rejection, there is escalation in the development of cutaneous malignancies in organ transplant patients a number of years after transplantation. Thus, with the expansion in these procedures over the past decades, and the ever-lengthening survival of these patients, we are seeing an increase in cutaneous malignancies in this patient population. OBJECTIVE: To determine if combined therapy with 5% 5-fluorouracil and 5% imiquimod may be useful in the treatment of squamous cell carcinoma in situ. METHODS: We present five renal transplant patients, all more than 10 years posttransplantation, three with insulin-dependent diabetes, who developed multiple areas of squamous cell carcinoma (SCC) in situ. All these patients were on chronic immunosuppressive chemotherapy to prevent rejection, but were otherwise doing well. All the patients had biopsy-proven SCC in situ on their lower extremities that even in normal patients may be a challenge to treat. RESULTS: We treated these five patients with a combination of a local immune therapy, imiquimod cream, and a topical chemotherapeutic agent, 5% 5-fluorouracil (5-FU), with clearing of the areas of SCC in situ. CONCLUSION: Although immunotherapy must be used with caution in organ transplant patients to avoid graft rejection, topical imiquimod is a local immune modulator that potentiates local innate and possible adaptive immunity without measurable effects on systemic immunity. In addition, there is evidence that cytokines induced by imiquimod may improve the therapeutic efficacy of topical 5% 5-FU in the treatment of SCC in situ.

Administration, Cutaneous↗

PubMed2001

Bowen's disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies. OBJECTIVE: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL. METHODS: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day. RESULTS: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy. CONCLUSION: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies.

Adjuvants, Immunologic↗

PubMed2001

Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis.

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.

Adult↗

PubMed2001

Spindle cell epithelioma of the vagina shows immunohistochemical staining supporting its origin from a primitive/progenitor cell population.

Spindle cell epitheliomas of the vagina (SCEVs) coexpresses epithelial and mesenchymal markers and were first described as a "mixed tumors of the vagina." However, unlike mixed tumors of other organs, which are believed to originate from myoepithelial cells, SCEVs neither immunohistochemically nor ultrastructurally show features of myoepithelial cells. The present expanded battery of immunohistochemical stains is presented on this rare tumor, including cytokeratin AE1/AE3, CK7, CK20, S100 protein, epithelial membrane antigen, alpha-smooth muscle actin, desmin, CD34, CD99, Bcl-2, vimentin, estrogen and progesterone receptors, and Ki-67. There was minimal expression of alpha-smooth muscle actin and negative staining with S100 protein, with coexpression of cytokeratins and vimentin and expression of estrogen and progesterone receptors, as previously reported in SCEVs. In addition, diffuse expression of CD34, CD99, and Bcl-2 immunohistochemical stains was found, which has not previously been reported. The coexpression of CD34, CD99, and Bcl-2 in SCEVs is consistent with its origin from a primitive/progenitor cell population.

Adult↗

PubMed2001

Delayed cutaneous hypersensitivity reactions to hirudin.

Hirudin is one of the new synthetic antithrombin agents, which is most commonly used in patients with type II heparin-induced thrombocytopenia and in patients with hypersensitivity reactions to unfractionated heparin as well as low-molecular-weight heparins. Hirudin is comparable to heparin as an antithrombotic agent and also has been studied as a primary treatment in patients who experienced acute myocardial infarctions. We describe a patient with a history of type II heparin-induced thrombocytopenia who was placed on intravenous hirudin therapy. After extravasation of the intravenous hirudin site, the patient developed a delayed hypersensitivity reaction that histologically showed an epithelioid granulomatous infiltrate. Although rare reports of hypersensitivity reactions to hirudin have been published, these reactions have not been well characterized and the histopathologic changes have not been described.

Biopsy↗

PubMed2000

Perspectives in dermatopathology: telomeres and telomerase in ageing and cancer; with emphasis on cutaneous disease.

Shortening of telomeres occurs with cell proliferation and correlates well with ageing in humans. Telomerase is a ribonucleoprotein, and is the body's most widely studied mechanism for extension of telomeres to circumvent cellular ageing. Telomerase levels remain at low or unmeasurable levels in most somatic cell populations with only a few exceptions. However, in transformed cell populations, upregulation of telomerase or some other mechanism for telomere extension is required for immortality. The telomere-telomerase system has been proposed to be an adaptation of organisms with prolonged lifespan to avoid malignant tumors, at the cost of the cellular dysfunctions associated with the aged phenotype. Therapies to modulate telomere length and telomerase levels hold promise for therapy of cancer and ageing as well as for genetic conditions that predispose to an aged phenotype.

Aging↗