Developing a prototype for integrated dental and diabetes care: understanding needs and priorities.

BACKGROUND: Periodontal treatment may be a useful adjunct to medical management of diabetes; however, oral health has not been integrated into multidisciplinary diabetes care in Australia. This study aimed to understand the needs of patients and staff at a diabetes clinic to inform a prototype of integrated dental and diabetes care. METHODS: Quantitative and qualitative data were collected from patients and staff at West Moreton Diabetes Clinic (WMDC) between September-October 2019. Clinical information, survey responses and dental screening results were analysed for 41 patients. Semi-structured interviews were held with six patients and a focus group with seven staff. RESULTS: Most patients (83%) had not seen a dentist in the previous year. Of the 37 patients with remaining natural teeth, 84% required periodontal assessment and 46% had multiple carious lesions. Unmet treatment needs and rates of access were similar for private and public dental patients. Staff and patients reported high levels of support for incorporation of dental care at WMDC. CONCLUSIONS: Integrating oral health into diabetes management is well-supported by patients and staff to address significant unmet dental needs for both public and private dental patients. Incorporating dental screening/services within diabetes clinics may increase uptake and improve awareness of its importance in diabetes management.

Dentomaxillofacial radiology in Australia and dentist satisfaction with radiology reports.

BACKGROUND: Dentomaxillofacial Radiology (DMFR) is comprised of the smallest cohort of specialists in Australia. A survey was undertaken to assess awareness of DMFR, radiology reporting and referring protocols as well as dental practitioners' satisfaction with their radiology reporting arrangements. METHODS: An original online survey created using Checkbox† was sent to dental practitioners. The survey was promoted on Australian-based dental Facebook forums and emailed to targeted members via Australian professional dental associations. RESULTS: A total of 399 responses were received, with over 80% of respondents aware of DMFR as a specialty. Approximately 40% of practitioners were self-reporting their imaging. There was correlation between increased satisfaction with external reporting and utilization of DMFR services and decreased satisfaction with medical radiology services. More than 90% of general dentists and greater than 85% of dental specialists prefer DMFR reports to medical radiology reports. Approximately 80% of practitioners believed that their satisfaction would change positively if they had access to a DMFR report. CONCLUSION: The research indicates a high degree of self-reporting or non-reporting by dental practitioners. There is low satisfaction with external reporting performed by Medical Radiologists primarily due to a lack of dental knowledge or detail and a preference for DMF Radiology reports.

A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults.

Population aging has prompted considerable interest in identifying modifiable factors that may help protect the brain and its functions. Collectively, epidemiological studies show that leisure activities with high mental and social demands are linked with better cognition in old age. The extent to which socio-intellectual activities relate to the brain's structure is, however, not yet fully understood. This systematic review and meta-analysis summarizes magnetic resonance imaging studies that have investigated whether cognitive and social activities correlate with measures of gray and white matter volume, white matter microstructure and white matter lesions. Across eighteen included studies (total n = 8429), activity levels were associated with whole-brain white matter volume, white matter lesions and regional gray matter volume, although effect sizes were small. No associations were found for global gray matter volume and the evidence concerning white matter microstructure was inconclusive. While the causality of the reviewed associations needs to be established, our findings implicate socio-intellectual activity levels as promising targets for interventions aimed at promoting healthy brain aging.

Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary.

BACKGROUND: Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease. OBJECTIVE: To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). METHODS: Qualitative: patient focus group and interviews to address content validity. Quantitative: secondary data analyses to test reliability and validity. RESULTS: Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male. Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure. Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male. Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score. Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively. VALIDITY: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms). RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05). E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001). CONCLUSIONS: Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD. Further study of sensitivity to change is warranted.

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis.

BACKGROUND: So far, no comprehensive answer has emerged to the question of whether transcranial direct current stimulation (tDCS) can make a clinically useful contribution to the treatment of major depression. We aim to present a systematic review and meta-analysis of tDCS in the treatment of depression. METHOD: Medline and Embase were searched for open-label and randomized controlled trials of tDCS in depression using the expressions ('transcranial direct current stimulation' or 'tDCS') and ('depression' or 'depressed'). Study data were extracted with a standardized data sheet. For randomized controlled trials, effect size (Hedges' g) was calculated and the relationships between study variables and effect size explored using meta-regression. RESULTS: A total of 108 citations were screened and 10 studies included in the systematic review. Six randomized controlled trials were included in the meta-analysis, with a cumulative sample of 96 active and 80 sham tDCS courses. Active tDCS was found to be more effective than sham tDCS for the reduction of depression severity (Hedges' g=0.743, 95% confidence interval 0.21-1.27), although study results differed more than expected by chance (Q=15.52, df=6, p=0.017, I2=61.35). Meta-regression did not reveal any significant correlations. CONCLUSIONS: Our study was limited by the small number of studies included, which often had small sample size. Future studies should use larger, if possible representative, health service patient samples, and optimized protocols to evaluate the efficacy of tDCS in the treatment of depression further.

Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression.

BACKGROUND: Neuropsychological impairment is a key feature of late-life depression, with deficits observed across multiple domains. However, it is unclear whether deficits in multiple domains represent relatively independent processes with specific neural correlates or whether they can be explained by cognitive deficits in executive function or processing speed. METHOD: We examined group differences across five domains (episodic memory; executive function; language skills; processing speed; visuospatial skills) in a sample of 36 depressed participants and 25 control participants, all aged ≥ 60 years. The influence of executive function and processing speed deficits on other neuropsychological domains was also investigated. Magnetic resonance imaging correlates of executive function, processing speed and episodic memory were explored in the late-life depression group. RESULTS: Relative to controls, the late-life depression group performed significantly worse in the domains of executive function, processing speed, episodic memory and language skills. Impairments in executive function or processing speed were sufficient to explain differences in episodic memory and language skills. Executive function was correlated with anisotropy of the anterior thalamic radiation and uncinate fasciculus; processing speed was correlated with anisotropy of genu of the corpus callosum. Episodic memory was correlated with anisotropy of the anterior thalamic radiation, the genu and body of the corpus callosum and the fornix. CONCLUSIONS: Executive function and processing speed appear to represent important cognitive deficits in late-life depression, which contribute to deficits in other domains, and are related to reductions in anisotropy in frontal tracts.

Persistence and adherence in the treatment of overactive bladder syndrome with anticholinergic therapy: a systematic review of the literature.

Overactive bladder syndrome (OAB) is a chronic condition that has an impact on patients' daily activities and health-related quality of life (HRQL). Anticholinergic therapy is often prescribed following insufficient results with behaviour modification alone; however, rates of treatment discontinuation are consistently high. This study systematically reviewed persistence and adherence data in patients with OAB treated with anticholinergic therapy. A search focused on the intersection of OAB, persistence/adherence, and anticholinergic therapy was conducted in MEDLINE and EMBASE. Articles published after 1998 were reviewed and selected for inclusion based on prespecified criteria. A total of 147 articles and two abstracts were included in the review. Results from 12-week clinical trials showed high rates of discontinuation, ranging from 4% to 31% and 5% to 20% in treatment and placebo groups, respectively. Unsurprisingly, rates of discontinuation found in medical claims studies were substantially higher, with 43% to 83% of patients discontinuing medication within the first 30 days and rates continuing to rise over time. Findings from medical claims studies also suggest that over half of patients never refill their initial prescription and that adherence levels tend to be low, with mean/median medication possession ratio (MPR) values ranging from 0.30 to 0.83. The low levels of persistence and adherence documented in this review reveal cause for concern about the balance between the efficacy and tolerability of anticholinergic agents. Strategies should be identified to increase persistence and adherence. New agents and non-pharmacologic alternatives with good efficacy and minimal side effects should be explored.

Assessing patients' descriptions of lower urinary tract symptoms (LUTS) and perspectives on treatment outcomes: results of qualitative research.

AIMS: Understanding the patient's experience and symptom descriptions is critical to assess outcomes. Thus, there is a need for qualitative research to better understand how patients describe their symptoms and treatment expectations. METHODS: Eight focus groups were conducted in two research phases: Phase 1 focused on eliciting patient's descriptions of urinary symptoms, and Phase 2 assessed patient perspectives on treatment outcomes. Participants with a range of lower urinary tract symptoms (LUTS) were recruited from urology clinics and community settings in the United States. All interviews were audio recorded and transcribed. Content and descriptive analyses were performed. RESULTS: A total of 33 men and 30 women participated. Mean ages for men and women were 55 and 61 in Phase 1, and 57 and 61 in Phase 2, respectively. About 73% of participants were white people, and most had a high school education or greater. A wide range of LUTS were emergently described, and the words, concepts and phrases were generally similar across groups. Most participants identified with the word 'bother', and thought it was important to assess both the frequency and bother of each symptom. Reasons for seeking care included symptom bother and fears about cancer and bladder infections. Most participants thought that a 50% improvement in a single symptom or group of symptoms would be a meaningful treatment outcome. CONCLUSION: This qualitative research provides a better understanding on how men and women describe their LUTS and their perspectives on treatment outcomes. This research can be used to inform the development of a new LUTS outcomes' tool.

Evaluating the Power of Food Scale in obese subjects and a general sample of individuals: development and measurement properties.

BACKGROUND: The Power of Food Scale (PFS) was developed to assess the psychological impact of today's food-abundant environments. OBJECTIVE: To evaluate the structure of the PFS in diverse populations of obese and nonobese individuals. DESIGN: Data were obtained from obese adults in a clinical trial for a weight management drug (n=1741), and overweight, obese and normal weight adults in a Web-based survey (n=1275). Exploratory and confirmatory factor analyses were used to investigate the PFS structure using the clinical data. The model developed was then tested using the Web-based data. Relationships between PFS domains and body mass index (BMI) were examined. Logistic regression was used in the Web-based survey to evaluate the association between obesity status and PFS scores. RESULTS: Clinical data indicated that the scale was best represented by a 15-item version with three subscale domains and an aggregate domain (average of three domains); this was confirmed with data from the Web-based survey (Comparative Fit Index: 0.95 and 0.94 for the clinical and Web-based studies, respectively). Cronbach's alpha for both data sets was high, ranging from 0.81 to 0.91. The relationships between BMI and each domain were weak (and approximately linear). A full category increase in PFS domain score (range 1-5) increased the odds of being obese 1.6-2.3 times. CONCLUSIONS: The 15-item PFS is best represented by three domains and an aggregate domain. The PFS may provide a useful tool to evaluate the effects of obesity treatments on feelings of being controlled by food in an obesogenic food environment.

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants.

BACKGROUND: The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale that measures three domains of eating behavior: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE). OBJECTIVES: To assess the factor structure and reliability of TFEQ-R21 (and if necessary, refine the structure) in diverse populations of obese and non-obese individuals. DESIGN: Data were obtained from obese adults in a United States/Canadian clinical trial (n=1741), and overweight, obese and normal weight adults in a US web-based survey (n=1275). Confirmatory factor analyses were employed to investigate the structure of TFEQ-R21 using baseline data from the clinical trial. The model was refined to obtain adequate fit and internal consistency. The refined model was then tested using the web-based data. Relationships between TFEQ domains and body mass index (BMI) were examined in both populations. RESULTS: Clinical data indicated that TFEQ-R21 needed refinement. Three items were removed from the CR domain, producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI)=0.91). Testing TFEQ-R18V2 in the web-based sample supported the revised structure (CFI=0.96; Cronbach's coefficient alpha of 0.78-0.94). Associations with BMI were small. In the clinical study, the CR domain showed a significant and negative association with BMI. On the basis of the web-based survey, it was shown that the relationship between BMI and CR is population-dependent (obese versus non-obese, healthy versus diabetics). CONCLUSIONS: In two independent datasets, the TFEQ-R18V2 showed robust factor structure and good reliability. It may provide a useful tool for characterizing UE, CR and EE.

Impact of adalimumab treatment on health-related quality of life and other patient-reported outcomes: results from a 16-week randomized controlled trial in patients with moderate to severe plaque psoriasis.

BACKGROUND: Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) are important in evaluating the impact of psoriasis and its treatment. OBJECTIVES: To assess the impact of adalimumab treatment on HRQOL and other PROs in patients with moderate to severe psoriasis. METHODS: A 16-week, double-blind, double-dummy, randomized controlled trial evaluated the efficacy and safety of adalimumab in 271 adults with moderate to severe chronic plaque psoriasis. Patients were randomized in a 2:2:1 ratio to adalimumab, methotrexate (MTX) or placebo. PROs were evaluated throughout the study and included the Dermatology Life Quality Index (DLQI), Patient's Global Assessment of disease severity, plaque psoriasis and psoriatic arthritis pain visual analogue scale (VAS), Psoriasis-Related Pruritus Assessment and EuroQOL 5D (EQ-5D). RESULTS: Statistically significant differences were observed between the adalimumab- and placebo-treated and the MTX-treated groups on mean DLQI total scores during the 16-week double-blind study (both P<0.001). Significant differences, favouring adalimumab compared with placebo, were also observed on the Patient's Global Assessment of disease severity (P<0.001), VAS for pain (P<0.001), Psoriasis-Related Pruritus Assessment (P<0.001), EQ-5D VAS (P<0.001) and EQ-5D index score (P<0.01). Compared with MTX, adalimumab resulted in statistically significantly greater improvements in the Patient's Global Assessment of disease severity (P<0.001), the VAS for pain (P<0.01) and the Psoriasis-Related Pruritus Assessment (P<0.001). CONCLUSIONS: Adalimumab was efficacious in improving dermatology-specific HRQOL, disease control and symptom outcomes in patients with moderate to severe psoriasis.

Generation and characterization of epidermolysis bullosa simplex cell lines: scratch assays show faster migration with disruptive keratin mutations.

BACKGROUND: Epidermolysis bullosa simplex (EBS) is an inherited skin fragility disorder caused by mutations in keratin intermediate filament proteins. While discoveries of these mutations have increased understanding of the role of keratins and other intermediate filaments in epithelial tissues, progress towards the development of therapy for these disorders is much slower. OBJECTIVES: Cell culture model systems that display these structural defects are needed for analysis of the cellular consequences of the mutations and to enable possible therapeutic strategies to be developed. Our aim was to generate immortalized cell lines as such model systems for the study of EBS. METHODS: We generated a series of stable cell lines expressing EBS-associated keratin mutations, by immortalizing keratinocytes from EBS-affected skin biopsies with either simian virus 40 (SV40) T antigen or human papillomavirus 16 (HPV16) E6/E7, and assessed their keratin expression (by immunofluorescence), proliferation rates and migratory behaviour (in outgrowth and scratch wound assays). RESULTS: Clonal immortalized keratinocyte cell lines KEB-1, KEB-2, KEB-3 (using SV40 T antigen) and KEB-4, KEB-7 and NEB-1 (using HPV16 E6/E7) were established. These include two lines from a single individual with Weber-Cockayne EBS (i.e. KEB-3 and KEB-4, mutation K14 V270M), and three cell lines from a second family, two from siblings carrying the same mutation (KEB-1, KEB-2 lines from Dowling-Meara EBS, mutation K5 E475G) and one from an unaffected relative (NEB-1). The sixth cell line (KEB-7), with a previously unreported severe mutation (K14 R125P), was the only one to show keratin aggregates in resting conditions. Despite variations in the immortalization procedure, there was no significant difference between cell lines in keratin expression, outgrowth capabilities or response to transient heat shock. However, cell migration, as measured by speed of scratch wound closure, was significantly faster in cells with severe EBS mutations. CONCLUSIONS: These cell lines provide useful culture systems in which to assess aspects of EBS-induced cell changes. The faster migration after scratch wounding of the EBS keratinocytes may be a consequence of the known upregulation of stress-activated kinase pathways in these cells.

Pregnancy-associated plasma protein-A accounts for the insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) proteolytic activity in human pregnancy serum and enhances the mitogenic activity of IGF by degrading IGFBP-4 in vitro.

Pregnancy-associated plasma protein-A (PAPP-A) has been identified as the insulin-like growth factor (IGF)-dependent IGF-binding protein-4 (IGFBP-4) protease produced by human fibroblasts. Recently, we found that serum proteases induced during human pregnancy cleaved IGFBP-4 in both an IGF-II-dependent and an IGF-II-independent fashion. This study sought to determine whether PAPP-A is the predominant IGFBP-4 protease in human pregnancy serum (PS) and to assess the in vitro role of serum PAPP-A. Immunoprecipitation with PAPP-A antibody effectively depleted PAPP-A from the PS and completely abolished both IGF-II-dependent and IGF-II-independent IGFBP-4 proteolytic activity in PS. Direct addition of PAPP-A antibody to PS completely blocked IGFBP-4 proteolysis and partially blocked IGFBP-5 proteolysis, but had no effect on IGFBP-3 proteolysis. To evaluate the role of serum PAPP-A, we tested whether PAPP-A in PS modulated the inhibitory activity of IGFBP-4 on IGF-II-induced cell proliferation in human osteosarcoma MG63 cells. The wild-type IGFBP-4 (WTBP-4; 200 ng/mL) failed to inhibit proliferation of the cells treated with PS (0.1% or 0.3%) alone or in combination with IGF-II (40 ng/mL), whereas the inhibitory effect of WTBP-4 was observed in the cells treated with nonpregnancy serum alone or in combination with IGF-II (P < 0.05). In contrast to WTBP-4, a protease-resistant IGFBP-4 was able to inhibit proliferation of the cells treated with PS alone or in combination with IGF-II (P < 0.05). In the presence of PAPP-A neutralizing antibody, the inhibitory effect of WTBP-4 on proliferation of the cells treated with IGF-II and PS was restored. In summary, these data demonstrate 1) that PAPP-A represents the predominant IGFBP-4 protease in PS; 2) that PAPP-A may in part contribute to IGFBP-5, but not IGFBP-3, proteolytic activity in PS; and 3) that PAPP-A enhances the bioactivity of IGFs in vitro by degrading IGFBP-4.

Spontaneous keratinocyte cell lines representing early and advanced stages of malignant transformation of the epidermis.

A unique series of epidermal cell lines representing different stages of malignant transformation were spontaneously derived from a single adult immunosuppressed individual. Four keratinocyte lines (PM1-4) established from forehead skin are here compared with 4 squamous cell carcinoma (SCC) lines (MET1-4) derived respectively from a primary cutaneous tumour, two local recurrences and a distant metastasis of invasive SCC. Despite altered growth properties, the PM lines retained many features of normal keratinocytes including keratin phenotype, differentiation capacity and non-tumorigenicity in athymic mice. In contrast, from early passage, the MET lines displayed markedly reduced growth requirements, abnormal differentiation, aberrant K18 expression and tumorigenicity in athymic mice. The abnormal keratin profile of individual MET lines closely reflected the keratin phenotype of the tumour of origin. Although unusual HPV types were identified in the original tissue, there was no evidence of persistent virus within any cell line and it appears that HPV is not critical for maintenance of the immortal phenotype. The PM lines were distinctly different from invasive SCC lines and are likely to be useful for studies of mutations important early in neoplastic progression. The SCC series represent primary, recurrent and metastatic carcinoma. Availability of such a series from the same individual will facilitate genetic analysis of the malignant process.

Increases in neutral, Mg2+-dependent and acidic, Mg2+-independent sphingomyelinase activities precede commitment to apoptosis and are not a consequence of caspase 3-like activity in Molt-4 cells in response to thymidylate synthase inhibition by GW1843.

Thymidylate synthase (TS) inhibition causes cell death, and this enzyme is the target for the important chemotherapy regime 5-fluorouracil/leucovorin. GW1843 (1843U89) is a potent and specific folate analog TS inhibitor in clinical development. Because of the importance of TS as a chemotherapy target, we are studying the mechanism of TS inhibition-induced cell death by GW1843. Ceramide is a regulatory lipid generated by the action of sphingomyelinase and is believed to signal apoptosis. The role of the ceramide in apoptotic signaling was studied in Molt-4 human T-cell leukemia cells undergoing cell death after treatment with GW1843. In response to GW1843, Molt-4 cells undergo apoptosis with both acidic pH, Mg2+-independent sphingomyelinase (ASMase) and neutral pH, Mg2+-dependent sphingomyelinase (NSMase) activities elevated as early steps in the initiation of apoptosis before Molt-4 commitment to death. These activities lead to ceramide production with kinetics consistent with a role as an effector molecule signaling the initiation of apoptosis in Molt-4 cells. These changes were found to be independent of caspase 3-like (CPP32/apopain) activity and DNA degradation, but were not separable from membrane blebbing or cell lysis in this cell line. In this report, kinetic evidence is provided for a role of ceramide in initiating GW1843-induced cell death of Molt-4 T-cell leukemia cells.

Tissue-specific cytokine production during experimental acute pancreatitis. A probable mechanism for distant organ dysfunction.

Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet. Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) mRNA and protein were detected within the pancreas early in the course of pancreatitis in both models, coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle. A significant delay between pancreatic and distant organ cytokine production was always observed. It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs.

Primary cutaneous Ewing's family sarcoma. Report of a case with immunostaining for glycoprotein p30/32 mic2.

The differential diagnosis of cutaneous small round cell malignancies is a relatively uncommon but recurrent problem that usually requires adjuvant techniques including special histochemical stains, immunohistochemistry (IHC), electron microscopy (EM), and cytogenetics (CG) to arrive at a definite answer. This report describes a case of a primary cutaneous malignancy that, after workup, fulfilled the criteria of extraskeletal Ewing's family sarcoma, which was corroborated by IHC with an antibody to glycoprotein p30/32 mic2 that is highly expressed in these neoplasms. The lesions consisted of a large nodular proliferation of poorly differentiated monotonous small round cells confined to the dermis and subcutaneous tissue. The cells had high nuclear to cytoplasmic (N/C) ratios, scattered prominent nucleoli, and indistinct cytoplasm. A periodic acid-Schiff (PAS) stain with and without diastase demonstrated abundant cytoplasmic glycogen. The glycogen was confirmed with EM, which did not show neurosecretory granules, but extensive sectioning of the tissue blocks demonstrated with light microscopy a single focus with pseudorosette formation. IHC was positive for monoclonal antibody (MAb) O13 to glycoprotein p30/32 mic2 and negative for lymphoid (CD45), neural (S-100, NF, GFAP), neuroendocrine (NSE), and muscle (MSA, desmin) markers. To the best of our knowledge, this is one of few reported cases of primary cutaneous (extraskeletal/extraosseous) Ewing's sarcoma (EEWS) and the first to use IHC with MAb O13, which recognizes the cell surface glycoprotein p30/32 mic2. This case further illustrates the continuum between EEWS and primitive peripheral neuroepithelioma and supports the unifying concept that these two entities are merely subtle morphologic variants of the same malignant neoplasm, which is better designated a Ewing's family sarcoma.

Mollaret's meningitis: case report with immunocytochemical and polymerase chain reaction amplification studies.

Mollaret's meningitis is a rare disease with a characteristic clinical course and distinctive cerebrospinal fluid (CSF) cytology. Although Mollaret originally described the large mononuclear cells seen in the CSF as endothelial, subsequent ultrastructural and immunocytochemical studies support a monocyte/macrophage lineage for these cells. To data, the pathogenesis of this entity remains uncertain, although an association with herpes simplex virus (HSV) has been reported in rare cases. In the current case study, immunocytochemistry for factor VIII-related antigen, leukocyte common antigen, and macrophage-specific antigen were performed and provide additional evidence of a monocyte/macrophage lineage for Mollaret cells. Polymerase chain reaction amplification for HSV DNA was done to further explore one possible etiology for this disease, but was negative.

Chondrosarcomatous cutaneous metastasis. A unique manifestation of sarcomatoid (metaplastic) breast carcinoma.

Breast carcinoma is the most common origin of cutaneous metastasis in women but is usually of ductal or lobular histotypes. Sarcomatoid (metaplastic) carcinoma of the breast, although a well-established aggressive neoplasm, is very uncommon. The metaplastic elements span all types of mesenchymal differentiation and have been demonstrated to be derived from carcinomatous elements. Skin metastasis from such lesions is extremely rare. A case of metastatic sarcomatoid breast carcinoma to the skin is described in which the histology of the metastases was that of chondrosarcoma.