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.
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 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
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
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
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.
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.
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.
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.
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.
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
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 versus 309 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.
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.
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.
Depression in Rheumatoid Arthritis and an Estimation of the Bi-directional Association of Depression and Disease Burden: A Dissertation
Depression is a common comorbidity in rheumatoid arthritis (RA), yet it may not be adequately recognized during routine clinical care. RA symptoms may confer a risk for depression, and vice versa; depression may affect RA disease activity and response to treatment. The study aims were to compare patient- and physician-reported depression measures, evaluate the temporal bi-directional association between RA disease activity and depressive symptomology, and assess depression as a moderator of RA treatment.
Patients were identified using a national RA registry sample (Consortium of Rheumatology Researchers of North America; CORRONA). Depression prevalence and incidence rates were estimated, and concordance and disagreement using measures reported separately by patients and physicians, as well as baseline cross-sectional associations between RA disease and a history of depression. A survival analysis was conducted to temporally predict the incident onset of self-reported depressive symptoms using the different metrics of RA disease activity. Also, mixed effects models were used to assess prospective changes in RA disease activity by prevalent and incident depressive symptom status. Lastly, logistic regression models compared the likelihood of clinical response to RA treatment during follow-up in those with and without depression when starting biologic disease modifying anti-rheumatic drug (DMARD) therapy.
Patient-reported depression rates were much higher and significantly different from physician based comorbidity estimates. Patient and physician RA disease activity measures were associated with an increased risk for depression onset, but not laboratory-reported serum biomarkers. Similarly, depression was temporally associated with significantly slower rates of decline regarding every patient-reported disease activity measure, some physician-reported metrics, but not acute phase reactants. Moreover, there was a significantly lower probability of achieving clinical remission among those with depression on a biologic DMARD after 6 months and an analogous effect at 12-months that was slightly lower in magnitude, which did not reach statistical significance.
Rheumatologists under-reported the occurrence of prevalent and incident depressive symptoms, and thus are likely unaware of its presence in their RA patients. Further, the results suggest the bi-directional effects between these conditions are related to the cognitive and behavioral aspects of depression and their interactions with disease activity, rather than shared immunological mechanisms in the context of cell-mediated immunity. When also considering the impact on clinical response to biologic DMARDS, the findings collectively imply that rheumatologists must address any challenges due to depression to provide the best care to their patients.
Secular trends in occurrence of acute venous thromboembolism: the Worcester venous thromboembolism study (1985 to 2009)
BACKGROUND: The clinical epidemiology of venous thromboembolism has changed recently due to advances in identification, prophylaxis, and treatment. We sought to describe secular trends in occurrence of venous thromboembolism among residents of the Worcester, Massachusetts, metropolitan statistical area (WMSA).
METHODS: Population-based methods were used to monitor trends in event rates of first-time or recurrent venous thromboembolism in 5025 WMSA residents diagnosed with acute pulmonary embolism and/or lower-extremity deep vein thrombosis during 9 annual periods between 1985 and 2009. Medical records were reviewed by abstractors and validated by clinicians.
RESULTS: Age- and sex-adjusted annual event rates for first-time venous thromboembolism increased from 73 (95% CI 64-82) per 100,000 in 1985/1986 to 133 (122-143) in 2009, due mostly to an increase in pulmonary embolism. The rate of recurrent venous thromboembolism decreased from 39 (32-45) in 1985/1986 to 19 (15-23) in 2003, and then increased to 35 (29-40) in 2009. There was an increasing trend in using non-invasive diagnostic testing, with about half of tests being invasive in 1985/1986 and almost all non-invasive by 2009.
CONCLUSIONS: Despite advances in identification, prophylaxis, and treatment between 1985 and 2009, the annual event rate of venous thromboembolism has increased and remains high. While these increases may be partially due to increased sensitivity of diagnostic methods, especially for pulmonary embolism, it may also imply that current prevention and treatment strategies are less than optimal.
Mini Symposia Program for the fifth annual UMass Center for Clinical and Translational Science Research Retreat, held Tuesday, May 20, 2014 at the Albert Sherman Center, University of Massachusetts Medical School, Worcester, MA. The program includes the Mini Symposia schedule and descriptions of each program.
List of posters presented during the Poster Session at the fifth annual UMass Center for Clinical and Translational Science Research Retreat, held Tuesday, May 20, 2014, at the Albert Sherman Center at the University of Massachusetts Medical School, Worcester, MA.
Recent breakthroughs in creating induced pluripotent stem cells (iPS cells) provide alternative means to obtain embryonic stem (ES) cell-like cells without destroying embryos by introducing four reprogramming factors (Oct3/4, Sox2, and Klf4/c-Myc or Nanog/Lin28) into somatic cells. However, the molecular basis of reprogramming is largely unknown. To address this question, we employed microRNAs, small molecules, and conducted genome-wide RNAi screen, to investigate the regulatory mechanisms of reprogramming.
First we showed that depleting miR-21 and miR-29a enhances reprogramming in mouse embryonic fibroblasts (MEFs). We also showed that p53 and ERK1/2 pathways are regulated by miR-21 and miR-29a and function in reprogramming.
Second, we showed that computational chemical biology combined with genomic analysis can be used to identify small molecules regulating reprogramming. We discovered that the NSAID Nabumetone and the anti-cancer drug OHTM could replace Sox2 during reprogramming. Nabumetone could also replace c-Myc or Sox2 without compromising self-renewal and pluripotency of derived iPS cells.
To identify the cell-fate determinants during reprogramming, we integrated a genome-wide RNAi screen with transcriptome analysis to dissect the molecular requirements in reprogramming. We found that extensive interactions of embryonic stem cell core circuitry regulators are established in mature iPS cells, including Utf1, Nr6a1, Tdgf1, Gsc, Fgf10, T, Chrd, Dppa3, Fgf17, Eomes, Foxa2. Remarkably, genes with non-differential change play the most critical roles in the transitions of reprogramming. Functional validation showed that some genes act as essential or barrier roles to reprogramming. We also identified several genes required for maintaining ES cell properties. Altogether, our results demonstrate the significance of miRNA function in regulating multiple signaling networks involved in reprogramming. And our work further advanced the reprogramming field by identifying several new key modulators.
The recurrent nature of the 3 most common vestibulopathies suggests a recurrent cause. Histopathology in temporal bones from patients with these syndromes - vestibular neuronitis (VN, n = 7), Meniere's disease (MD, n = 8) and benign paroxysmal positional vertigo (BPPV, n = 5) - shows focal degeneration of vestibular nerve axons and degenerated nearby facial nerve meatal ganglion cells. Transmission electron microscopic confirmation of intracytoplasmic viral particles in surgically excised vestibular nerves from patients with VN and MD support a viral etiology in these vestibulopathies. Antiviral treatment of these syndromes in a series of 211 patients with a 3- to 8-year follow-up resulted in complete control of vertigo in VN (88%), MD (90%) and BPPV (60%).