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Biomedical subjects

H Skelton

Publications and source records attributed to H Skelton.

At least 37 records · Page 2Linked to original sources

The cutaneous cellular infiltrate to stingray envenomization contains increased TIA+ cells.

Stingrays result in approximately 2000 stings annually in the U.S.A., and thus are one of the most important venomous marine animals. After envenomization, there is immediate, intense pain with subsequent oedema, cyanosis followed by local erythema and petechiae. Progressive local necrosis and ulceration is variable, sometimes leading to gangrene. To characterize the inflammatory infiltrate at the site of a stingray injury, we examined tissue obtained approximately 4 days after stingray envenomization. Routine histology and immunohistochemical stains for lymphoid markers, including CD3, CD4, CD8, CD20, KP-1 and TIA were performed, and demonstrated a central area of haemorrhagic necrosis with a surrounding infiltrate of lymphoid cells and eosinophils. Approximately one-third of the mononuclear cells were TIA+, and these cells appeared mainly to correspond to the cells which were CD3+ and CD4+. The inflammatory cells, including the lymphoid populations, suggest that an immunological reaction may contribute to the delayed healing of stingray injuries.

Adult↗

Cholesterol metabolsim defect associated with Conradi-Hunerman-Happle syndrome.

We present a 6-week-old black girl with Conradi-Hunerman-Happle syndrome (CHS). The mother had no past medical history of illness, and the pregnancy progressed normally to a spontaneous vaginal delivery at 36 weeks. There was no known significant family history. A diagnosis of chondrodysplasia punctata was made at birth from physical examination and X-ray findings. On physical examination at 6 weeks, a koala face, a saddle nose, and a right-sided cataract were noted (Fig. 1a,b). There was unilateral left-sided ichthyosis well demarcated at the midline, with whorled brown fine scale following Blashko's lines on the patient's right side. Orthopedic complications were bilateral but were more pronounced on the left side. There was bilateral shortening of the humerus, with polydactyly of the right hand, arachnodactyly of the left fingers, bilateral clubbing, and mild contractures of the feet. X-Rays showed multiple calcifications along the spine, proximal and distal femoral epiphysis, and proximal humeral epiphysis (Fig. 2). The patient was treated with emollients (aquaphor) twice daily with continuing improvement in ichthyosis. The clubbed feet were treated with splinting and the polydactyly was corrected by surgery. Ophthalmology was to follow the patient for her right-sided cataract. At the patient's 4-month follow-up, the ichthyosis showed a marked improvement with some residual hypo- pigmented atrophoderma noted. The distribution remained unchanged. Biopsies taken of ichthyotic lesions showed compact hyperkeratosis and follicular plugging. Vesicles within the stratum corneum contained amorphous material (Fig. 3a,b). The granular cell layer was thickened with retained oval nuclei. The epidermal and adnexal epithelium were disorganized. Increased apoptotic/dyskeratotic keratinocytes were seen within the epidermis, but were most evident within the follicular epithelium. Ultrastructural studies showed saccular dilations of the acellular space within the stratum corneum. These acellular spaces were filled with unprocessed lamellated pleated sheets and vesicle complexes and processed lamellae. Dyskeratotic cells were seen within the stratum spinosum. Red blood cell (RBC) plasmalogen levels and polyunsaturated fatty acids (PUFA), including decosahexaenoic acid (DHA), were within normal limits. Plasma very long chain fatty acids (VLCFA), including C26 : 0/C22 : 0 ratios, phytanic and pristanic acids, plasmalogen, and phytanic/pristanic ratios, trihydroxycholestanic acid (THCA) and dihydroxycholestanoic acid (DHCA) including their ratios, THCA/cholic acid and DHCA/chenodeoxycholic acid, and PUFAs including DHA were within normal limits. Urine organic acids and piecolic acid were within normal limits. Despite these normal values, there was an increase in cholest-8(9)-en-3beta-ol of 6.8 microg/mL (normal, 0.01-0.10 microg/mL) and an increase in 8-dehydrocholesterol (5.1 microg/mL) (normal, <0.10 microg/mL).

Abnormalities, Multiple↗

Histopathologic features seen in Gianotti-Crosti syndrome secondary to Epstein-Barr virus.

BACKGROUND: Gianotti-Crosti syndrome (GCS) or infantile papular acrodermatitis presents as a symmetric erythematous lichenoid papular and papulovesicular eruption of the face, extremities, and buttocks, usually occurring in young children. GCS has been associated with hepatitis B and enteroviruses, as well as Epstein-Barr virus (EBV) and, rarely, cytomegalovirus. OBJECTIVE: The purpose of this study was to use immunohistochemical studies to determine the pattern of the lymphoid infiltrate and evidence for viral antigens in cases of EBV-associated GCS. METHODS: Routine histologic and immunohistochemical stains were evaluated in 3 patients with typical GCS. All 3 patients showed serologic evidence of an acute EBV infection. The immunohistochemical studies included monoclonal antibodies for CD3, CD4, CD8, CD20, TIA, S-100 protein, KP-1, EBV latent membrane antigen-1, and EBV-encoded nuclear antigen-2. RESULTS: All biopsy specimens showed minimal epidermal spongiosis with marked papillary dermal edema. The associated inflammatory infiltrate showed a mixed mononuclear cell infiltrate with rare eosinophils. Immunohistochemical stains for latent membrane antigen-1 and EBV-encoded nuclear antigen-2 were negative for EBV. The majority of mononuclear cells showed membrane staining for CD3, 30% to 40% of the CD3 mononuclear cells showed positive staining for CD4, and 50% to 60% showed positive staining with CD8. TIA(+) cells appeared to correspond to the CD8(+) cells. CONCLUSION: Although papillary dermal edema has been reported within the spectrum of histologic findings in GCS, it was marked and a consistent finding in the 3 cases in which EBV was the most likely etiologic agent. The presence of large numbers of cytotoxic T cells in the inflammatory infiltrate may have accentuated this histologic finding and may be a relatively distinctive histologic finding with GCS associated with EBV.

Acrodermatitis↗

Lichen planopilaris-like changes arising within an epidermal nevus: does this case suggest clues to the etiology of lichen planopilaris?

BACKGROUND: Lichen planopilaris shows a perifollicular lymphocytic infiltrate at the level of infundibulum and the isthmus of the hair bulge resulting in necrotic changes within keratinocytes and eventually hair loss. OBJECTIVE: We present a 14-year-old black male with a history of a raised epidermal lesion on the scalp that was present at birth. Over the past few years, the patient developed gradual hair loss and increased verrucous changes of the skin within the original lesion. Histologic sections of the area showed features consistent with an epidermal nevus peripherally, with a central area showing some features characteristic of those seen in lichen planopilaris. In addition, there was marked hyperkeratosis with increased yeast and bacteria within the follicles. CONCLUSIONS: Initiating factors in lichen planopilaris are not well defined. Overgrowth of microorganisms with hyperkeratosis results in factors that disrupt the immune privilege of the hair follicle, leading to an immunologic reaction that is limited to the follicle and spares surrounding eccrine structures. This case suggests possible mechanisms involved in the induction of lichen planopilaris.

Adolescent↗

Imiquimod therapy for molluscum contagiosum.

BACKGROUND: Molluscum contagiosum virus (MCV) is a large double-stranded DNA virus that is a member of the family Poxviridae, and which has a worldwide distribution. As with other poxviruses, MCV does not appear to develop latency but evades the immune system through the production of viral specific proteins. OBJECTIVE: To evaluate the therapeutic efficacy of imiquimod 5% cream for MCV. METHODS: Thirteen children >5 and <10 years old, 19 immune-competent adults and four adults with advanced, but stable HIV-1 disease with >10 MCV lesions were treated with topical 5% imiquimod cream three times weekly for up to 16 weeks. RESULTS: Fourteen of 19 immune-competent adults, four of four adults with HIV-1 disease, and six of 13 children had resolution of their MCV lesions in <16 weeks of imiquimod therapy. Children tended to have more pruritus and inflammatory reactions with imiquimod, although most treated lesions appeared to respond. The development of new MCV lesions resulted in a lower overall resolution of the lesions in children. Imiquimod appeared to be the most efficacious in patients with HIV-1 disease and in the genital area in immune-competent adults. CONCLUSION: Although topical imiquimod appears to have some efficacy in the therapy of MCV, in children the pruritus correlated relatively well with the development of new lesions. In adults, areas that would be expected to have better penetration appeared to respond more consistently. Although the HIV-1-positive patients had the largest clinical lesions at the onset of therapy, as a group they had the best overall response to therapy.

AIDS-Related Opportunistic Infections↗

Lamivudine (3TC)-induced contact dermatitis.

The nucleoside analogue lamivudine (3TC) is commonly used in multidrug therapy of human immunodeficiency virus-1 disease because it not only potentiates the antiviral effects of other reverse transcriptase inhibitors, but it is also relatively nontoxic. We present a patient who developed a contact dermatitis to lamivudine after prolonged exposure.

Adult↗

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↗

Accelerated growth of dermatofibrosarcoma protuberans during pregnancy.

Dermatofibrosarcoma protuberans (DFSPs) are uncommon skin tumors that have a high incidence of local recurrence even with wide surgical margin, but DFSPs rarely metastasize. Previous reports have suggested that DFSPs may enlarge more rapidly during pregnancy. We report 3 additional cases of DFSPs that showed accelerated growth during pregnancy. Immunohistochemical stains for CD34, S-100 protein, factor XIIIa, and estrogen and progesterone receptors were performed on biopsy specimens. The tumors in all 3 patients, and 4 additional DFSPs from 2 male and 2 female subjects, showed expression of progesterone receptor. As with many other stromal neoplasms, DFSPs appear to express low levels of hormone receptors, which may be one factor that accounts for their accelerated growth during pregnancy.

Adult↗

Adjuvant therapy with hyaluronidase prior to excision of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade cutaneous malignancies, which rarely metastasize. Although surgery is the main therapy for these tumors, they commonly recur in spite of wide excisions. Hyaluronidase (HD) has been used both intralesionally as well as intravenously as an adjuvant in therapy of both epithelial and mesenchymal malignancies to decrease local spread, to potentiate differentiation induced apoptosis, and to potentiate the tissue penetration of chemotherapeutic agents. In addition, there is a long history of intralesional HD use without significant complications. The biologic characteristics of DFSP including the observation that hyaluronic acid is commonly present and sometimes is increased in these tumors and the known effects of HD therapy in other malignancies suggested to us that HD pretreatment may be a helpful adjuvant in the surgical management of DFSPs. Following diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with intralesional HD injections. RESULTS: Based on margins necessary for complete excision from past studies, this patient had decreased margin width and thus had a postoperative wound size less than was expected. The patient has had no evidence of recurrence at 24 months follow-up.

Chemotherapy, Adjuvant↗

Stromal progenitor cells present within liposuction and reduction abdominoplasty fat for autologous transfer to aged skin.

BACKGROUND: Autologous fat is used for direct transfer to locally replace fat, as well as for use intradermally in the treatment of rhytids in aged skin. OBJECTIVE: To determine if the components of the autologous fat could be separated to produce a better agent for the treatment of rhytids. METHODS: Liposuction material from four patients and fat from abdominoplasty from five patients was processed by homogenization and centrifugation to separate mature lipocytes from other stromal cell populations in its associated extracellular matrix, and then to separate this from the blood and cellular debris. The cellular layer was evaluated histologically and with the immunohistochemical antibodies for CD34, SM-actin, S-100 protein, MIB-1, Bcl-2, and factor XIIIa. RESULTS: The cellular layer showed spindle cells, some small vascular structures, a small amount of mature fat, and extracellular matrix. CD34 showed diffuse staining of most spindle and endothelial cells in all sections, factor XIIIa showed only focal staining of spindle and dendritic cells, and Bcl-2 showed light to moderate staining in scattered cells within the cellular component. S-100 protein, SM-actin, and MIB-1 were negative. CONCLUSION: Processed liposuction and abdominoplasty processed fat may be ideal for the treatment of wrinkles in aged skin because it contains progenitor stromal cells that are known to be present within the fat and which may be concentrated by processing methods.

Abdomen↗

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↗

Pretreatment with intralesional hyaluronidase prior to excision of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSPs) are an uncommon malignancy that commonly recur, but rarely metastasize. The origin of DFSPs is controversial; however, they stain with the progenitor marker CD34. DFSPs usually show increased stromal mucin, mainly hyaluronic acid (HA). HA increases cellular proliferation, delays differentiation and increases cellular motion. We evaluated the pretreatment of DFSPs with intralesional injections of hyaluronidase (HD) prior to the surgical excision. Five of nine cases of DFSPs were pretreated with HD. In HD-pretreated cases the margins for excision of the residual tumor were reduced. HD pretreatment also decreased CD34 staining and increased polarizable collagen in the residual tumor.

Adult↗

Drug screening of patients who deliberately harm themselves admitted to the emergency department.

This study was a retrospective analysis of drugs present in blood and urine samples taken from patients (n = 200) admitted to the emergency department of a major teaching hospital with a provisional diagnosis of deliberate self-harm. The aim was to assess the current limited drug screening strategy to see whether it needed to be changed in any way. Drugs present in blood and urine were identified by immunoassay or chromatography, categorized, and concentration-toxicity effects evaluated when practicable. For each case, the various drugs/drug classes detected were correlated with those reported by the patient. A questionnaire evaluation of doctor's perceptions of the influence of the primary blood drug screen on patient destinations was administered. The rapid primary drug screen using a blood/plasma sample detected some 46% of all drugs identified. The doctors considered that it was influential in deciding on immediate patient destination, and therefore, it is likely to be a cost-effective measure. In addition, the screen detected toxic concentrations of drugs in a significant proportion of patients who did not report their ingestion correctly. A primary drug screen using a urine sample detected opiates, cannabinoids, and amphetamines but such detection was considered unlikely to alter short-term treatment. A high-performance liquid chromatography and gas chromatography-mass spectroscopy secondary screen using blood and urine detected a significant number of additional drugs, but was slow, costly, and not likely to alter short-term treatment. The authors conclude that the primary screen for alcohol, benzodiazepines, paracetamol, salicylate, and tricyclic antidepressants remains the optimal drug screening strategy. Quantitative or qualitative estimation of patient-reported drugs such as quinine, theophylline, verapamil, and antiepileptics may be justifiable in individual patients.

Adolescent↗

Cutaneous epithelioid schwannomas: a rare variant of a benign peripheral nerve sheath tumor.

Although benign epithelioid peripheral nerve sheath tumors have been described, they are rare, and benign epithelioid schwannomas have not yet been established as a specific histologic variant. We present four cases of tumors which we believe would meet criteria to be classified as benign epithelioid schwannomas. Biopsy specimens obtained from four different patients were examined with routine and immunohistochemical staining. All the tumors were well-circumscribed lesions that were surrounded by a capsule containing EMA-positive cells. The cellular component was composed of epithelioid cells, in which there was a lack of mitotic activity. Immunohistochemical studies showed the tumor cells were S-100 protein and Leu 7 positive and HMB-45 negative. In addition, type IV collagen encircled individual cells within the tumor, indicating a continuous basal lamina. We report a group of cutaneous epithelioid schwannomas. Although the presence of such tumors is not unexpected, this diagnosis may not be initially considered because of this rare cytologic feature.

Adult↗