Search

Objective: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old)., Method: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores., Results: Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores., Conclusion: The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use's impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.

Langerhans cell histiocytosis is a rare and clinically heterogeneous group of dendritic histiocytic disorders with typical onset in the neonatal period or infancy, although it can present at any age. Histiocytes accumulate in one or more organs, leading to a variable clinical presentation of disease. We report a case of biopsy-proven Langerhans cell histiocytosis in a newborn and discuss the workup and management of this disease, along with reviewing its clinical variants., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 by S. Karger AG, Basel.)

Muir-Torre syndrome, a Lynch syndrome variant, is characterized by sebaceous neoplasia plus one or more malignancies, typically colon cancer. The significance of DNA mismatch repair (MMR) deficiency detection by immunohistochemistry (IHC) in colorectal carcinomas is well established and is recommended as a screening tool for Lynch syndrome in newly diagnosed colorectal carcinomas. In comparison, literature on IHC application to detect MMR proteins (MLH1, MSH2, MSH6, and PMS2) in sebaceous neoplasia has been less studied and has been derived almost exclusively from tertiary care centers. Herein we describe the largest series to date characterizing MMR deficiency in sebaceous neoplasms, as well as the relative frequencies of each deficiency. Two hundred sixteen consecutive sebaceous neoplasms (216 patients) were analyzed from a community practice setting (133 sebaceous adenomas, 68 sebaceomas, 15 sebaceous carcinomas). One hundred forty-three were MMR deficient (66%), of which 90 were MSH2/MSH6 deficient (63%), 27 MLH1/PMS2 deficient (19%), 22 MSH6 deficient (15%), and 4 PMS2 deficient (3%). MMR deficiency was significantly associated with site, with tumors off of the head and neck more likely to be MMR deficient (specificity 96%). In contrast to prior reports, no significant trend in MMR-deficient versus -nondeficient tumors was seen in age at presentation (median age, 68 versus 66), tumor-infiltrating lymphocytes, or tumor type. Given the low sensitivity of age < 60 years (30%), location off of the head and neck (41%), or presence of tumor-infiltrating lymphocytes (29%) in MMR deficiency detection, IHC screening programs should test all sebaceous neoplasms for MMR deficiency, regardless of their clinicopathological features., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We present a case of a 33-year-old female who was incidentally found to have cutaneous leiomyomata during a routine skin examination. Further history revealed that she also suffered from uterine fibroids and that her mother had died at an early age from renal cell carcinoma. This case serves as a reminder of the often-subtle cutaneous clues, as well as the importance of a multidisciplinary approach, for early diagnosis of potentially fatal conditions.

Vascular anomalies may be appropriately classified into two broad categories, vascular tumors and vascular malformations, which are distinguished by the presence of cellular proliferation in contrast to aberrations in morphogenesis, respectively. This system of classification is based upon histological features that may in large part be differentiating, but nevertheless, may show morphological overlap. Advances in immunophenotyping allow for more precise diagnoses as well as further delineation of cell origins. In the discussion, we present the clinical, histological, and, when applicable, the immunophenotypic presentation of vascular anomalies commonly seen in infancy and early childhood., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process., (Copyright © 2011 John Wiley & Sons A/S.)

Background: De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD) is a newly characterized lesion that is associated with a personal and/or family history of malignant melanoma (MM) and/or dysplastic nevi (DN). However, the biological significance is still uncertain and the persons predisposed to this lesion have not been adequately described., Methods: Clinicopathologic data of 258 patients, from 263 biopsies diagnosed with DNIEMD, was obtained. A brief voluntary questionnaire was used to obtain demographic, risk factor and disease history., Results: There is an 82% (n=263) predominance of women with DNIEMDs. For men and women, the distributions of these lesions occur on the lower extremities (71%), the upper extremities (24%) and trunk (5%). Thirty-one percent of the 258 patients responded to the questionnaires. 48% of the 60 respondents had green or blue eyes. 26% of 62 respondents had a history of non-melanoma skin cancer (NMSC). Combined data revealed that 68% of 134 patients had a history of DN. As well, 24% of 89 patients had personal histories of melanoma, while 24% of 72 patients had a family history of melanoma., Conclusion: Most of these DNIEMD lesions are found on the lower extremities of women and men, and they have an increased association with MM, DN and NMSC.

Incontinentia pigmenti (IP), or Bloch-Sulzberger syndrome, is a rare X-linked dominant genodermatosis primarily affecting females. Although IP affects many organ systems, the hallmark feature of this disease is its characteristic cutaneous eruption along the lines of Blaschko that evolves through four distinct stages: inflammatory/vesiculobullous, verrucous, hyperpigmented and hypopigmented/ atrophic. We describe a case of IP in its vesicular stage that completely resolved with topical Protopic (tacrolimus) 0.1% ointment. The treatment successfully halted the progression of disease through its subsequent disfiguring stages.

It has been postulated that phospholipases of fungal origin can affect in vitro susceptibility testing of amphotericin B lipid complex (ABLC). We used specific phospholipase-deficient mutants of Candida albicans and Cryptococcus neoformans in susceptibility testing and demonstrated that extracellular fungal phospholipase activity does not influence the in vitro susceptibilities of these two fungi to ABLC.

Terbinafine has previously been shown to be highly active against dermatophytes and many other filamentous fungi. However, its activity against yeasts is controversial, with earlier reports suggesting that it has low activity, while more recent studies demonstrated that terbinafine is effective against yeasts. In this study, the in vitro activity of terbinafine was evaluated against a broad range of fungal isolates. We examined the susceptibility of 100 yeast strains (10 species including Candida albicans, non-C. albicans, fluconazole-susceptible and -resistant candidal strains), and 184 strains of filamentous fungi and dermatophytes (29 species including Aspergillus, Fusarium, Sporothrix, Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis and Epidermophyton floccosum), using the NCCLS M27-A microdilution methodology for yeasts and a modified M38-P methodology for moulds. The endpoint for terbinafine was defined as 80% inhibition compared with the growth control well. The mean yeast and filamentous fungi minimum inhibitory concentration values +/- SEM (in microg ml(-1)) for terbinafine were: 6.60 +/- 0.73 and 1.04 +/- 0.28, respectively. In conclusion, our data suggest that terbinafine, in addition to its potent activity against dermatophytes, is considerably effective against a broad range of yeasts and filamentous fungi in vitro. Therefore, investigations concerning its antifungal activity in vivo against such organisms should be pursued.

A standardized reference method for dermatophyte in vitro susceptibility testing is lacking. In a previous study, Norris et al. (H. A. Norris, B. E. Elewski, and M. A. Ghannoum, J. Am. Acad. Dermatol. 40(6, part 2):S9-S13) established the optimal medium and other growth variables. However, the earlier study did not address two issues: (i) selection of an optimal medium for conidial formation by dermatophytes and (ii) validation of the method with a large number of dermatophytes. The present study addresses these two points. To select which agar medium best supported conidial growth, representative isolates of dermatophytes were grown on different agars. Preliminary experiments showed that only oatmeal cereal agar supported the production of conidia by Trichophyton rubrum. We tested the abilities of 251 T. rubrum isolates to form conidia using three different cereal agars and potato dextrose agar. Overall, oatmeal cereal and rice agar media were comparable in their abilities to support T. rubrum conidial growth. Next, we used the oatmeal cereal agar for conidial formation along with the optimal conditions for dermatophyte susceptibility testing proposed by Norris et al. and determined the antifungal susceptibilities of 217 dermatophytes to fluconazole, griseofulvin, itraconazole, and terbinafine. Relative to the other agents tested, terbinafine possessed the highest antifungal activity against all of the dermatophytes. The mean +/- standard error of the mean MICs of fluconazole, itraconazole, terbinafine, and griseofulvin were 2.07 +/- 0.29, 0.13 +/- 0.01, 0.002 +/- 0.0003, and 0.71 +/- 0.05 microgram/ml, respectively. This study is the first step in the identification of optimal conditions that could be used for the standardization of the antifungal susceptibility testing method for dermatophytes. Inter- and intralaboratory agreement as well as clinical correlations need to be established.

We investigated the in vitro activity of voriconazole compared to those of fluconazole and itraconazole against 566 clinical isolates of Cryptococcus neoformans from Africa (164) and the United States (402). Isolates were obtained from cerebrospinal fluid (362), blood (139), and miscellaneous sites (65). Voriconazole (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 to 0.25 microg/ml) was more active than either itraconazole (MIC90, 0.5 microg/ml) or fluconazole (MIC90, 8.0 to 16 microg/ml) against both African and U. S. isolates. Isolates inhibited by >/=16 microg of fluconazole per ml were almost all (99%) inhibited by

We compared the yeast nitrogen base (YNB) broth microdilution method with the National Committee for Clinical Laboratory Standards (NCCLS) M27-A microdilution reference method for measuring the in vitro susceptibility of Cryptococcus neoformans isolates to fluconazole. A total of 149 isolates of C. neoformans var. neoformans from Ugandan AIDS patients was tested by both methods. An overall agreement of 88% between the two microdilution methods was observed. All isolates grew well in both RPMI 1640 and YNB media, and MICs could be read after 48 h of incubation by both methods. The range of fluconazole MICs obtained with the YNB method was broader than that obtained with the NCCLS method. The extended range of MICs provided by the YNB method may be of clinical value, as it appears that the clinical outcome may be better among patients infected with strains inhibited by lower concentrations of fluconazole as determined by the YNB method. The YNB method appears to be a viable option for testing C. neoformans against fluconazole.

MICs for clinical Candida and Cryptococcus isolates were determined by a method incorporating the colorimetric indicator 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] -2H-tetrazolium hydroxide (XTT), and the results were compared with MICs obtained by the National Committee for Clinical Laboratory Standards approved standard method (M27-A). One hundred percent of all isolates demonstrated agreement within 2 dilutions between the MICs of amphotericin B, fluconazole, itraconazole, ketoconazole, and flucytosine obtained by the two methods. These data suggest that an XTT-based method could provide a useful means for the determination of antifungal susceptibility of yeasts.