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Microcystic adnexal carcinoma. Case report and review of the literature

Mon, 06/02/2014 - 3:05pm

Microcystic adnexal carcinoma is an aggressive, locally destructive cutaneous neoplasm with a high rate of recurrence. This tumor is often misdiagnosed clinically and histologically. It usually occurs in middle-aged to older adults. We describe a 44-year-old man with a large microcystic adnexal carcinoma that was present for more than 20 years. The tumor invaded the perichondrium, muscle, nerve, and blood vessel adventitia. A review of the literature suggests that these tumors are often histologically misdiagnosed because the biopsy specimens may be too small to reveal all the characteristic histologic features. The clinical presence of marked induration, a smooth surface, and, possibly, sensory changes should alert the clinician to the possibility of this neoplasm. The initial biopsy specimen must be large enough to demonstrate the identifying histologic features. Mohs surgery is currently the treatment of choice for microcystic adnexal carcinoma, as it often spreads far beyond clinically evident tumor.

Arsenic in Dermatology

Mon, 06/02/2014 - 3:05pm

BACKGROUND: Arsenic is a chemical carcinogen that exists naturally and in the workplace.

OBJECTIVES: Review exposure, clinical signs of arsenic exposure, and the carcinogenic potential.

METHOD: Review of literature.

RESULTS: Arsenic is a known carcinogen that occurs both naturally and in the workplace. It causes cutaneous malignancies, hyperpigmentation, palmer and plantar keratosis, and internal malignancies, especially of the lung and bladder.

CONCLUSION: Exposure risks need to be well publicized. Those people with known exposure need regular full skin exams as well as close follow-up by their primary care physician.

Stump the experts. Apocrine hidrocystoma

Mon, 06/02/2014 - 3:05pm

Malignant melanoma with clinical and histologic features of Merkel cell carcinoma

Mon, 06/02/2014 - 3:05pm

We describe a patient with malignant melanoma that resembled a Merkel cell carcinoma both clinically and histologically. Immunohistochemical studies showed focally positive staining with S-100 protein and strongly positive staining with HMB-45. Ultrastructural study confirmed the diagnosis by demonstrating premelanosomes and melanosomes. Although the tumor appeared to be clinically unimpressive, it was a deep melanoma with a Breslow level of 3.8 mm that necessitated aggressive treatment. Small cell melanoma must be considered in the differential diagnosis of small cell tumors, which also includes lymphoma, eccrine carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. The diagnosis of amelanotic melanoma, including the small cell variant, may require electron microscopic studies.

Management of a hidradenoma with Mohs micrographic surgery

Mon, 06/02/2014 - 3:05pm

BACKGROUND: Hidradenomas are adnexal tumors that may grow to be very large and frequently recur after excision. Malignant transformation and metastatic spread can occur and histologic distinction of benign from malignant hidradenomas can be very difficult. Some tumors with bland histology have demonstrated aggressive behavior.

OBJECTIVE: To decide the benefits of management with Mohs micrographic surgery of large hidradenomas.

METHODS: The literature was reviewed, including both the clinical course of the tumor and histologic features. The case of our report was interpreted in light of the review.

RESULTS: Three stages of Mohs surgery were required for complete removal of the hidradenoma. The patient remains free of recurrence.

CONCLUSION: This report highlights the difficulties in distinguishing benign from malignant hidradenomas and emphasizes the benefits of Mohs surgery for large or recurrent tumors.

Frequency of postoperative allergic contact dermatitis to topical antibiotics

Mon, 06/02/2014 - 3:05pm

BACKGROUND AND DESIGN: Topical antibiotics are one of the most common causes of allergic contact dermatitis and are frequently used in postoperative wound care. We prospectively followed up patients having cutaneous surgery to determine the frequency of allergic contact dermatitis to topical antibiotics used on postoperative wound care.

RESULTS: Nine (4.2%) of 215 patients who had undergone surgery who were using a topical antibiotic had an eruption develop postoperatively that was consistent with an allergic contact dermatitis from the topical antibiotic. Seven of the nine patients agreed to patch testing with the standard tray and selected topical antibiotics. Five patients had a positive patch test to neomycin sulfate and four had a positive patch test to bacitracin. The frequency of allergic contact dermatitis proved by patch testing to neomycin and bacitracin is five (5.3%) of 94 and four (2%) of 198, respectively, in the patients who used these antibiotics. All proved sensitivities to bacitracin occurred in patients using a topical antibiotic that also contained neomycin and were patch tested positive to the neomycin. No patients using only pure bacitracin had allergic contact dermatitis.

CONCLUSIONS: Allergic contact dermatitis to a topical antibiotic, especially neomycin, should be considered in any patient who has development of a dermatitis after cutaneous surgery. Because of the frequency of allergic contact dermatitis, neomycin-containing antibiotics should be avoided in postoperative wound care.

Pigmented basal cell carcinoma: investigation of 70 cases

Mon, 06/02/2014 - 3:05pm

BACKGROUND: Pigmented basal cell carcinoma (PBCC) is a clinical and histologic variant of BCC.

OBJECTIVE: Our purpose was to identify the histologic subtypes of BCC that were most often associated with pigment and to determine whether this correlated with outcome after excision.

METHODS: A series of PBCC was identified and the histologic subtype noted. Margins of all excisions were examined for residual tumor. These results were then compared with a series of nonpigmented BCCs.

RESULTS: In a series of 1039 consecutive BCCs, 70 (6.7%) contained pigment. The histologic growth pattern most frequently associated with pigment was the nodular/micronodular pattern (12.4%) followed by the nodular (7.7%), superficial (7.2%), micronodular (4.0%), and the nodular/micronodular/infiltrative (3.4%) patterns. Margins were examined for evidence of residual tumor in the 40 cases that were excised. In only one case (2.5%) was the margin positive for tumor. This was statistically significant (p less than 0.05) compared with 388 excisions of nonpigmented BCCs with comparable growth patterns in which 69 (17.7%) showed positive margins.

CONCLUSION: PBCC, as a clinical variant, is more frequently excised with adequate margins than are tumors of comparable histologic subtypes that do not contain pigment.

Cytomegalovirus diaper dermatitis

Mon, 06/02/2014 - 3:05pm

Cytomegalovirus inclusions have been reported in perineal ulcers from immunosuppressed adults. The importance of this finding is unknown. We report the first pediatric case of cutaneous cytomegalovirus infection in an infant with congenital human immunodeficiency virus infection, presenting as a diaper dermatitis. Cytomegalovirus was cultured from the skin biopsy specimen, and characteristic inclusions were seen on hematoxylin-eosin-stained sections. Results of this biopsy specimen analysis prompted further investigation revealing disseminated cytomegalovirus infection, including retinitis. Aggressive pursuit of a pathogen in common conditions such as diaper dermatitis is strongly recommended in immunosuppressed pediatric patients.

Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms

Mon, 06/02/2014 - 3:05pm

This study attempts to define histologic patterns in 1039 consecutive cases of basal cell carcinoma and to correlate these patterns with adequacy of margins of surgical excision. Five major histologic patterns were identified: nodular, 218 cases (21%); superficial, 181 cases (17%); micronodular, 151 cases (15%); infiltrative, 77 cases (7%); and morpheic, 11 cases (1%). A mixed pattern (two or more major histologic patterns) was present in 401 cases (38.5%). Our study indicates that nodular and superficial basal cell carcinomas can be completely removed by simple surgical excision in a high percentage of cases (93.6% and 96.4%, respectively) whereas the micronodular, infiltrative, and morpheic basal cell carcinomas have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision. Mixed patterns that consisted of combinations of the nodular, micronodular, or infiltrative types exhibited a behavior similar to the pattern that resulted in a greater chance of incomplete surgical removal.

Pruritic urticarial papules and plaques of pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy

Mon, 06/02/2014 - 3:05pm

Thirty women who were seen at our institution between 1984 and 1988 for pruritic urticarial papules and plaques of pregnancy (PUPPP) were retrospectively evaluated and interviewed. We found a significantly increased maternal weight gain and newborn birth weight in patients with PUPPP, compared with age and parity-matched controls. The average weight gain during pregnancy was 18.1 +/- 0.9 (SEM) kg for the patients with PUPPP (excluding twin gestations) and 14.6 +/- 1.0 kg for the controls. The mean newborn birth weight was 3.6 +/- 0.09 kg for the PUPPP group and 3.3 +/- 0.08 kg for the control group. There were three twin pregnancies (10%), compared with the twin gestation rate at our institution of 1.6%. Therefore, based on our findings of an increased maternal weight gain and neonatal birth weight, an increased twin rate, and an abdominal eruption that occurs in primigravidas in their third trimester of pregnancy, we suggest that abdominal distention or a reaction to it may play a role in the development of PUPPP.

Lipids in the pathogenesis of ichthyosis: topical cholesterol sulfate-induced scaling in hairless mice

Mon, 06/02/2014 - 3:05pm

Although several abnormalities of lipid metabolism have been associated with abnormal cornification in humans, evidence that these lipids directly provoke abnormal scale is lacking. One recently described example of a lipid abnormality in ichthyosis is absence of the enzyme steroid sulfatase in recessive X-linked ichthyosis (RXLI). This enzyme normally desulfates cholesterol sulfate (CS) and sulfated steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). As a result of this enzyme deficiency, patients with RXLI accumulate CS in their blood and skin. To determine whether sulfated sterols are the specific cause of increased scale, we applied CS, DHEAS, cholesterol, or vehicle alone to the backs of hairless mice. In animals treated with CS, but not with DHEAS or with vehicle, visible scale without erythema appeared after 1 week, peaked at 2 weeks, and then diminished. When the dose of CS was doubled, abnormal scale reappeared and then decreased again. CS-induced scale was reversible, clearing within 3 days of discontinuation of treatment. Because there was no acanthosis, dermal inflammation, abnormal transepidermal water loss, or increased labeling index, it appears that the 3-fold increase in thickness of the stratum corneum in CS-treated animals is due to a direct effect on this layer.

Febrile ulceronecrotic Mucha-Habermann's disease

Mon, 06/02/2014 - 3:05pm

A patient with febrile ulceronecrotic Mucha-Habermann's disease manifested the characteristic features of this entity. These include a polymorphous eruption with histopathologic findings of Mucha-Habermann's disease, large ulceronecrotic skin lesions, intermittent high fever, and constitutional symptoms. The patient was unique in that he also had malabsorption and eosinophilia. This disease may represent a hypersensitivity reaction. To our knowledge, there are five previous cases of febrile ulceronecrotic Mucha-Habermann's disease reported in the world literature.

An easy method for removal of syringoma

Mon, 06/02/2014 - 3:05pm

Syringomas pose a cosmetic problem in some patients. In the past, surgical removal of large portions of the lower lid or electrodesiccation have been the usual methods of removal. This report describes a technique for individual excision of these tumors that is easily performed as an office procedure using a pair of fine ophthalmologic spring-action scissors and gives excellent cosmetic results.

Using Structured Telephone Follow-up Assessments to Improve Suicide-Related Adverse Event Detection

Fri, 05/30/2014 - 1:51pm

Adverse event (AE) detection and reporting practices were compared during the first phase of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE), a suicide intervention study. Data were collected using a combination of chart reviews and structured telephone follow-up assessments postenrollment. Beyond chart reviews, structured telephone follow-up assessments identified 45% of the total AEs in our study. Notably, detection of suicide attempts significantly varied by approach with 53 (18%) detected by chart review, 173 (59%) by structured telephone follow-up assessments, and 69 (23%) marked as duplicates. Findings provide support for utilizing multiple methods for more robust AE detection in suicide research.

How to Keep A Job: The Young Adults Guide

Wed, 05/28/2014 - 12:10pm

Starting and keeping a new job can be stressful for anyone. However, there are healthy ways to deal with this stress. This tip sheet has some tips to help you be more prepared to start and keep a new job, and hopefully be a little less stressed.

Utility Players: A Library's Research Services Easily Integrate into Translational Science Support

Wed, 05/28/2014 - 9:18am

Describes how an institutional repository of scholarly publications and other library services can be utilized to support the dissemination of translational science research by providing access to an institution's published research, collecting and archiving grey literature, publicizing individual and department collections, and measuring research impact via usage statistics.

Presentation during the National Program Committee Section on Translational Research, Medical Library Association Annual Meeting, May 2012, Seattle, WA.

Evening Snacking in Relation to Self-reported Declines in Sleep Quality during Pregnancy: Preliminary Results from the Decision-Making, Eating, and Weight Gain during Pregnancy (DEW) Study

Tue, 05/27/2014 - 9:20am

Background: Poor sleep in non-pregnant adults has been associated with increased evening snacking, which may contribute to weight gain. Sleep disturbances are common during pregnancy.

Objective: To examine the association between changes in sleep quality from pre-pregnancy and evening snacking.

Methods: In an ongoing prospective cohort study, pregnant women were recruited from UMMHC obstetric practices and the community. Participants are 18+ years, with singleton gestation <36 weeks, pre-pregnancy BMI 18.5-40 kg/m2, English-speaking, and with plans to deliver at UMMHC. Participants were asked “compared to the three months before you became pregnant, how is your sleep quality now?”; we combined responses of “about the same”/“a little better”/“a lot better” versus “a little worse”/“much worse”. Participants completed three 24-hour dietary recalls (2 weekdays, 1 weekend day). Evening snacks were defined as eating occasions after dinner but before bedtime during which food items other than water was consumed. Fisher’s Exact tests and t-tests provided comparisons for evening snacking (yes/no), number of snacks, and energy intake.

Results: Women with complete data (n=55) were 58% non-Hispanic White and aged 30.0 (SD: 4.3) years; gestational age at study visit was 23.0 (SD: 5.9) weeks. Of 866 meals reported, 94 were evening snacks. 71% (n=39) reported that their current sleep quality was worse than before pregnancy. Evening snacks were reported by 90% of women reporting worse sleep and 69% same/better (p=0.1028). While the number of snacks among snackers did not differ by change in sleep quality (M[SD]: 2.2[1.2] versus 1.6[0.8], p=0.2372), energy intake from these snacks was higher among women whose sleep quality had declined (M[SD]: 630[488] versus 309[331] kcal, p=0.0480).

Conclusions: Declines in sleep quality during pregnancy may be linked to evening snacking. More research is needed to understand the role of sleep quality, eating behavior, and weight gain during pregnancy.

Data from: The Vitamin D Status in Inflammatory Bowel Disease

Thu, 05/22/2014 - 2:43pm

This data set is the primary data source for the study that investigated the status of Vitamin D in children with inflammatory bowel disease (IBD). Manuscript has been submitted for publication by the authors.

Context: There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

Aim: To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

Hypothesis: Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

Subjects and Methods: A case-controlled retrospective study of subjects with IBD (n=58) of 2-20 years (male n=31, age 16.38 ± 2.21 years; female n=27, age16.56 ± 2.08 years) and healthy controls (n=116; male n=49, age 13.90 ± 4.59 years; female n=67, age 15.04 ± 4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (/mL) ( /L), overweight as BMI of ≥85th but <95th percentile, and obesity as BMI ≥95th percentile. Data were expressed as mean ± SD.

Results: Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69 ± 24.43 nmol/L, 53.26 ± 25.51, and 65.32 ± 27.97 respectively (ANOVA, p=0.196).

The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p=0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p=0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls.

However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p=0.025), as well as controls (65.3 ± 28.0 nmol/L vs. 49.5 ± 25.23, p = 0.045).

Conclusion: There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.

Studies of HLA-DM in Antigen Presentation and CD4+ T Cell Epitope Selection: A Dissertation

Thu, 05/22/2014 - 12:32pm

Antigen presented to CD4+ T cells by major histocompatibility complex class II molecules (MHCII) plays a key role in adaptive immunity. Antigen presentation is initiated by the proteolytic cleavage of pathogenic or self proteins and loading of resultant peptides to MHCII. The loading and exchange of peptides to MHCII is catalyzed by a nonclassical MHCII molecule, HLA-DM (DM). It is well established that DM promotes peptide exchange in vitro and in vivo. However, the mechanism of DM-catalyzed peptide association and dissociation, and how this would affect epitope selection in human responses to infectious disease remain unclear. The work presented in this thesis was directed towards the understanding of mechanism of DM-mediated peptide exchange and its role in epitope selection.

In Chapter II, I measured the binding affinity, intrinsic dissociation half-life and DM-mediated dissociation half-life for a large set of peptides derived from vaccinia virus and compared these properties to the peptide-specific CD4+ T cell responses. These data indicated that DM shapes the peptide repertoire during epitope selection by favoring the presentation of peptides with greater DM-mediated kinetic stability, and DM-susceptibility is a strong and independent factor governing peptide immunogenicity.

In Chapter III, I computationally simulated peptide binding competition reactions and found that DM influences the IC50 (50% inhibition concentration) of peptides based on their susceptibility to DM, which was confirmed by experimental data. Therefore, I developed a novel fluorescence polarization-based method to measure DM-susceptibility, reported as a IC50 (change in IC50 in the absence and presence of DM). Traditional assays to measure DM-susceptibility based on differential peptide dissociation rates are cumbersome because each test peptide has to be individually labeled and multiple time point samples have to be collected. However, in this method developed here only single probe peptide has to be labeled and only single reading have to be done, which allows for fast and high throughput measure of DM-susceptibility for a large set of peptides.

In Chapter IV, we generated a series of peptide and MHCII mutants, and investigated their interactions with DM. We found that peptides with non-optimal P1 pocket residues exhibit low MHCII affinity, low kinetic stability and high DM-susceptibility. These changes were accompanied with conformational alterations detected by surface plasmon resonance, gel filtration, dynamic light scattering, small-angle X-ray light scattering, antibody-binding, and nuclear magnetic resonance assays. Surprisingly, all these kinetic and conformational changes could be reversed by reconstitution with a more optimal P9 pocket residue. Taken together, our data demonstrated that conformation of MHCII-peptide complex constrained by interactions throughout the peptide binding groove is a key determinant of DM-susceptibility.

B cells recognizing cognate antigen on the virion can internalize and process the whole virion for antigen presentation to CD4+ T cells specific for an epitope from any of the virion proteins. In turn, the epitope-specific CD4+ T cells provide intermolecular (also known as noncognate or heterotypic) help to B cells to generate antibody responses against any protein from the whole virion. This viral intermolecular help model in which CD4+ T cells provide help to B cells with different protein specificities was established in small size influenza virus, hepatitis B virus and viral particle systems. For large and complex pathogens such as vaccinia virus and bacteria, the CD4+ T cell-B cell interaction model may be complicated because B cells might not be able to internalize the large whole pathogen. Recently, a study in mice observed that CD4+ T cell help is preferentially provided to B cells with the same protein specificity to generate antibody responses against vaccinia virus. However, for larger pathogens such as vaccinia virus and bacteria the CD4+ T cell-B cell interaction model has yet to be tested in humans. In Chapter V, I measured in 90 recently vaccinated and 7 long-term vaccinia-immunized human donors the CD4+ T cell responses and antibody responses against four vaccinia viral proteins (A27L, A33R, B5R and L1R) known to be strongly targeted by cellular and humoral responses. We found that there is no direct linkage between antibody and CD4+ T cell responses against each protein. However, the presence of immune responses against these four proteins is linked together within donors. Taken together, our data indicated that individual viral proteins are not the primary recognition unit and CD4+ T cells provide intermolecular help to B cells to generate robust antibody responses against large and complicated vaccinia virus in humans.