Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance].

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups. PATIENTS AND METHODS: In a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N = 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression. RESULTS: Lower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction = 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS. CONCLUSIONS: The association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers. GOV IDENTIFIER: NCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.

Comparative evaluation of MCP gene in worldwide strains of Megalocytivirus (Iridoviridae family) for early diagnostic marker.

Members of the Iridoviridae family have been considered as aetiological agents of iridovirus diseases, causing fish mortalities and economic losses all over the world. Virus identification based on candidate gene sequencing is faster, more accurate and more reliable than other traditional phenotype methodologies. Iridoviridae viruses are covered by a protein shell (capsid) encoded by the important candidate gene, major capsid protein (MCP). In this study, we investigated the potential of the MCP gene for use in the diagnosis and identification of infections caused Megalocytivirus of the Iridoviridae family. We selected data of 66 Iridoviridae family isolates (53 strains of Megalocytivirus, eight strains of iridoviruses and five strains of Ranavirus) infecting various species of fish distributed all over the world. A total of 53 strains of Megalocytivirus were used for designing the complete primer sets for identifying the most hypervariable region of the MCP gene. Further, our in silico analysis of 102 sequences of related and unrelated viruses reconfirms that primer sets could identify strains more specifically and offers a useful and fast alternative for routine clinical laboratory testing. Our findings suggest that phenotype observation along with diagnosis using universal primer sets can help detect infection or carriers at an early stage.

Incidence and prevalence of idiopathic interstitial pneumonia and idiopathic pulmonary fibrosis in Korea.

SETTING: Although the incidence and prevalence of idiopathic interstitial pneumonia (IIP) and idiopathic pulmonary fibrosis (IPF) have been assessed in Western countries, their epidemiology has not been analysed in Asian countries, including the Republic of Korea. OBJECTIVE: To estimate the prevalence and incidence of IIP, including IPF, in Korea, using a large, nationwide database. DESIGN: The Health Insurance Review and Assessment Services claims database, which includes information on every patient with diagnostic codes for IPF and IIP from 2010 to 2013, was reviewed. Age- and sex-specific IPF and IIP prevalence and incidence rates were estimated. RESULTS: Among Korean males and females, IPF prevalence from 2010 to 2013 was estimated at respectively 39.7 and 24.3 per 100 000 population, while IIP prevalence was estimated at respectively 97.1 and 66.5/100 000. The annual incidence rates among Korean males and females during 2011 and 2012 were respectively 16.4 and 9.7/100 000, for IPF, and respectively 42.3 and 27.5/100 000 for IIP. CONCLUSIONS: IPF is more prevalent in Korea than previously reported; its prevalence may be similar to or higher than in the United States and in European countries.

Peptide fragment of thymosin ß4 increases hippocampal neurogenesis and facilitates spatial memory.

Although several studies have suggested the neuroprotective effect of thymosin ß4 (TB4), a major actin-sequestering protein, on the central nervous system, little is understood regarding the action of N-acetyl-serylaspartyl-lysyl-proline (Ac-SDKP), a peptide fragment of TB4 on brain function. Here, we examined neurogenesis-stimulative effect of Ac-SDKP. Intrahippocampal infusion of Ac-SDKP facilitated the generation of new neurons in the hippocampus. Ac-SDKP-treated mouse hippocampus showed an increase in ß-catenin stability with reduction of glycogen synthase kinase-3ß (GSK-3ß) activity. Moreover, inhibition of vascular endothelial growth factor (VEGF) signaling blocked Ac-SDKP-facilitated neural proliferation. Subchronic intrahippocampal infusion of Ac-SDKP also increased spatial memory. Taken together, these data demonstrate that Ac-SDKP functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss.

Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.

Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. We found that early apoptotic cell death of the immature neurons occurred in the DG region following transient forebrain ischemia/reperfusion in mice. Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3ß/ß-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice.

Development of an encapsulation-vitrification protocol for Rubia akane (nakai) hairy roots: a comparison with non-encapsulation.

BACKGROUND: A comparison of different cryopreservation techniques should be based on the characteristics of both the methodology and the material in question using an optimized procedure. OBJECTIVE: This study aimed at developing an encapsulation-vitrification procedure for hairy roots of Rubia akane using alternative loading and vitrification solutions, based on the existing optimized droplet-vitrification procedure. MATERIALS AND METHODS: Encapsulated roots were first precultured in liquid medium with 10% sucrose for 3 days, then with 17.5 % sucrose for 1 day, after which they were osmoprotected with solution C6-40 % (20 % glycerol + 20 % sucrose) for 50 min, cryoprotected with solution A3-90 % (37.5 % glycerol + 15 % DMSO + 15 % EG + 22.5 % sucrose, w/v) on ice for 40 min, cooled and warmed in 2 ml cryovials, and unloaded in 35% sucrose solution for 60 min. RESULTS: Through the application of this procedure to aged-clustered roots, up to 97.5 % post-cryopreservation regeneration was observed. In our previous study, droplet-vitrification of hairy roots of R. akane resulted in 83.8 % post-rewarming regeneration following preculture with 10 % sucrose for 2 days and 17.5 % sucrose for 4-5 h, and osmoprotection with solution C4-35 % (17.5 % glycerol + 17.5 % sucrose) for 30 min, and cryoprotection with solution A3-70 % (29.2 % glycerol + 11.7 % DMSO + 11.7% EG + 17.4% sucrose, w/v) on ice for 20 min. In the present study, higher post-cryopreservation regeneration was observed by using a higher concentration of vitrification solution (A3-70 % → A3-90 %, B5-80 % → B1-100 %) and/or a longer cryoprotection duration (A3-70 % at room temperature (RT) for 8 min → 15-30 min, on ice for 20 min → 40-80 min; B5-80 % for 15 min → 30-60 min). CONCLUSION: Even though encapsulation provided some degree of protection from the cytotoxicity of vitrification solutions to cytotoxicity-sensitive R. akane hairy roots, an overall higher post-cryopreservation regrowth was obtained using the droplet-vitrification procedure under optimized conditions. This result implies that this sensitive material was not sufficiently cryoprotected, and thus, rapid cooling and warming using foil strips was more efficient than cryopreservation of encapsulated samples.

Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study.

BACKGROUND: Isotretinoin has been frequently used for acne therapy. However, it has limitation in acceptance because of its adverse effects. Although antihistamine recently revealed to decrease the lipogenesis, evidence is lacking regarding the clinical relevance of antihistamine in the treatment of acne. OBJECTIVES: To evaluate the clinical efficacy and tolerability of antihistamine as an adjuvant treatment of isotretinoin. METHODS: Forty patients with moderate acne were included in this randomized, controlled comparative study. Twenty patients were treated with isotretinoin and 20 patients were treated with additional antihistamine, desloratadine. Assessment was made at baseline, after 2, 4, 8 and 12 weeks of treatment. RESULTS: At week 12, compared with isotretinoin only group, isotretinoin with additional antihistamine group showed more statistically significant decrease in acne lesion counts (non-inflammatory lesions: 44.8% vs. 17.8%; inflammatory lesions: 55.8% vs. 22.9%; total lesions: 45.6% vs. 18.7%; all P < 0.05). Significant decrease was also observed in the score of global acne grading system and the measured value of sebum and erythema. Moreover, acne flare during the treatment occurred less frequently and adverse events of isotretinoin were more tolerable in additional antihistamine group. CONCLUSIONS: This results provide early evidence that antihistamine has a synergic effect with minimizing the side-effect of isotretinoin, and may be used as an adjuvant treatment of moderate acne.

Dose-related effect of urinary cotinine levels on pulmonary function among Korean women.

SETTING: Country-wide general population in South Korea. BACKGROUND: The dose-response relationship between smoking and pulmonary function in women may have been significantly over-estimated by studies that employed a self-reporting questionnaire. OBJECTIVE: To evaluate whether this relationship was still observed among Korean women when smoking levels were determined by urinary cotinine measurements. DESIGN: A total of 4584 Korean women from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included. Analysis of covariance was performed to estimate the dose-related effect of urinary cotinine levels on pulmonary function after adjusting for covariates in this country-wide cross-sectional study. RESULTS: Compared to urinary cotinine levels (cut-off 50 ng/ml), the false-positive rate of self-reported smoking was 53.2%. After the smokers were divided into deciles, the regression coefficients for percentage forced expiratory volume in 1 second (FEV1%) and percentage forced expiratory volume/forced volume capacity (FEV1/FVC) ratio (FEV1/FVC%) were -0.2903 and -0.2680 (%/decile), respectively (both P < 0.001). CONCLUSION: It is necessary to use objective methods when determining the smoking status of Korean women. Even after reducing information bias, smoking affected pulmonary function in a dose-dependent manner.

Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are known to be associated with response to primary systemic therapy (PST) in breast cancer. This study was conducted to assess the association of TIL subsets with pathological complete response (pCR) after PST in breast cancer in relation to breast cancer subtype, breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition (EMT). METHODS: The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+ TILs), BCSC phenotype, and the expression of EMT markers were evaluated by immunohistochemistry and were correlated with pCR after PST. RESULTS: Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated with pCR, and CD8+ TILs were found to be an independent predictive factor for pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in subgroup analyses. CONCLUSION: These findings indicate that CD8+ cytotoxic T lymphocytes are a key component of TILs associated with chemo-response and can be used as a reliable predictor of response to anthracycline- or anthracycline/taxane-based PST in breast cancer.

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.

BACKGROUND: The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas. METHODS: MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma. RESULTS: Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis. CONCLUSION: MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

High FOXP3+ regulatory T-cell density in the sentinel lymph node is associated with downstream non-sentinel lymph-node metastasis in gastric cancer.

BACKGROUND: We aimed to evaluate the immunologic nature of sentinel lymph nodes (SLNs) in gastric cancer patients and to determine whether it can predict non-SLN metastasis. METHODS: Sentinel lymph node samples were collected from 64 gastric carcinoma patients who had undergone gastrectomy with SLN biopsy. One representative SLN sample was selected from each patient and was subjected to immunostaining for CD8, CD57, FOXP3, and DC-LAMP. The numbers of marker-positive cells in each sample were counted. The relationships between various immune cell densities and clinicopathologic parameters or metastasis status of SLNs and non-SLNs were sought. RESULTS: High FOXP3+ Treg density of the SLN was found to be significantly associated with the presence of metastasis in either SLNs or non-SLNs. DC-LAMP+ cell density of the SLN was the highest at the isolated tumours cell level, and this decreased along with an increase in tumour metastasis in either SLNs or non-SLNs. Univariate and multivariate logistic regression models revealed that high FOXP3+ Treg density of the SLN was an independently significant predictor of non-SLN metastasis. CONCLUSIONS: This study is the first to indicate an important role of SLNs in metastatic dissemination of gastric cancer. Our findings suggest that Tregs could be a new therapeutic target for regulating the metastasis of gastric cancer.

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer.

BACKGROUND: The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer. METHODS: Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry. RESULTS: A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen. CONCLUSION: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.

Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer.

The study aims to determine whether type and density of tumour-infiltrating lymphocytes (TILs) can predict the clinical course in gastric cancer. Gastric carcinomas (n=220) were immunostained for CD3, CD8, CD20, and CD45RO and evaluated for clinicopathologic characteristics. Number of TILs that immunostained positively for each marker were counted using NIH ImageJ software. Tumours were grouped into low- and high-density groups for each marker (CD3, CD8, CD45RO). The densities of CD3(+), CD8(+), and CD45RO(+) TILs were found to be independent predictors of lymph node metastasis by multivariate analysis with odds ratios (95% CI) of 0.425 (0.204-0.885), 0.325 (0.150-0.707), and 0.402 (0.190-0.850), respectively. Kaplan-Meier survival analysis revealed that patients in the high-density groups for CD3, CD8, and C45RO had a significantly longer survival time than the patients in the corresponding low-density groups, respectively. In multivariate survival analysis, the densities of CD3(+), CD8(+), and CD45RO(+) TILs remained independent prognostic factors with hazard ratios (95% CI) of 0.549 (0.317-0.951), 0.574 (0.347-0.949), and 0.507 (0.298-0.862), respectively. In conclusion, density of TILs was found to be independently predictive of regional lymph node metastasis and patient survival in gastric cancer.

Characteristics of KIT-negative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining.

AIMS: To characterise KIT-negative gastrointestinal stromal tumours (GISTs) clinically, pathologically, immunohistochemically and genetically, and to establish the usefulness of protein kinase C theta (PKC) as a diagnostic marker in KIT-negative GIST. METHODS: 252 consecutive cases of GIST were evaluated for clinicopathological characteristics and immunostained for various antibodies. Mutational analyses of KIT and platelet-derived growth factor receptor alpha (PDGFRA) were also performed in 62 cases. RESULTS: 20 (7.9%) GISTs showed negative immunostaining for KIT. KIT-negative GISTs were more likely to originate from omentum or peritoneum, have an epithelioid histology, and be classified as high risk. The overall survival rate of patients with KIT-negative GISTs (5-year survival rate 68.7% (SD 10.7%)) was lower than that of patients with KIT-positive GISTs (5-year survival rate, 79.9% (3.0%)) (p = 0.042, log-rank test). Negative KIT expression was an independent prognostic factor in multivariate Cox regression analysis when the risk of aggressive behaviour and the status of imatinib treatment were adopted as covariates. KIT-negative GISTs also showed lower expression rates of CD34, Bcl-2, and PKC than KIT-positive GISTs; mutational analysis revealed that 30% of KIT-negative GISTs harboured a PDGFRA exon 18 mutation. Immunostaining on PKC showed that 93.9% of all GISTs expressed PKC protein. However, 21.9% of 64 mesenchymal tumours other than GIST also showed positivity on PKC. CONCLUSIONS: KIT-negative GISTs had characteristics that differ from those of KIT-positive GISTs, and negative KIT expression was an independent prognostic indicator for overall survival of patients. Although PKC is a sensitive diagnostic marker for GIST, its usefulness is limited because of low sensitivity and low specificity in KIT-negative GISTs.

EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number.

AIMS: Epidermal growth factor receptor (EGFR) expression has been observed in a variety of solid tumours with the potential of new targeted therapeutic agents. The aim was to evaluate the EGFR status of gastric carcinoma (GC) using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). METHODS AND RESULTS: The EGFR status was evaluated in GC tissues from 511 patients using IHC and FISH. In addition, the clinicopathological characteristics were examined and the results were compared with the EGFR status. One hundred and forty cases (27.4%) showed EGFR overexpression by IHC. EGFR overexpression was associated with older age (P = 0.001), moderately or poorly differentiated histology (P = 0.001) and higher stage disease (P = 0.046). Sixteen cases (3.1%) showed high polysomy and 12 cases (2.3%) had gene amplification by FISH. The correlation between IHC and FISH results was statistically significant (P < 0.001). The patients with GC who had EGFR overexpression had an unfavourable prognosis and multivariate analysis showed that EGFR overexpression was a possible independent unfavourable prognostic factor. CONCLUSIONS: EGFR overexpression was observed in a subset of cases with GC and was associated with an unfavourable prognosis. It will be important to evaluate EGFR status to interpret future clinical trials properly using EGFR targeted agents.

The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer.

AIM: To investigate the effect of polysomy 17 on HER-2 status as evaluated by immunohistochemistry (IHC), dual-colour fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH). METHODS: Dual-probe FISH and single-probe CISH were performed to detect HER-2 gene amplification, and IHC to detect HER-2 expression, on 309 invasive breast cancers. RESULTS: Polysomy 17 was detected in 32.0% of the total number of breast cancers; it was detected in 12.3% of the IHC 0 or 1+ cases, 42.8% of the IHC 2+ cases and 66.0% of the IHC 3+ cases (p<0.001). In addition, there was a substantially higher rate of polysomy 17 in the IHC 2+ or 3+/FISH-negative cases than in the IHC 0 or 1+ cases (40.8% vs 12.3%; p<0.001). The FISH and CISH results were concordant in 299 cases (96.8%). Of the 10 discordant cases, FISH suggested amplification in five with disomy 17 and one with monosomy 17, whereas CISH pointed to borderline copy numbers in each of these six cases. The remaining four cases had high polysomy 17; CISH, but not FISH, indicated amplification. CONCLUSIONS: Results suggest that an increase of HER-2 gene copy number secondary to polysomy 17 leads to HER-2 overexpression in some IHC 2+/3+ breast cancers, without gene amplification. The high level of concordance between FISH and CISH suggests that CISH is a valid alternative to FISH for assessing HER-2 gene amplification. However, cases in which CISH indicates the presence of borderline copy numbers or low levels of amplification may need FISH to rule out polysomy 17 and to determine HER-2 gene amplification status accurately.

Carcinoma erysipelatoides from squamous cell carcinoma of unknown origin.

Carcinoma erysipelatoides, also known as inflammatory metastatic carcinoma, is a rare form of cutaneous metastasis from a malignancy. The characteristic histopathological finding is metastatic tumour cells inside the dermal lymphatic ducts. It is frequently observed in patients with breast carcinoma as well as adenocarcinoma of pancreas, rectum, lung, ovary and parotid gland. We present a 66-year-old man diagnosed to have metastatic squamous cell carcinoma by aspiration cytology from an enlarged neck lymph node and a core biopsy of a left axillary mass. He subsequently received radiotherapy; however, due to intolerance to erythema and swelling on local irradiated skin, radiotherapy was deferred. Skin lesions on upper chest and neck area, consisting of erythematous induration with telangiectasia and tenderness, progressed slowly and were treated as cellulitis. The erythema remained stationary with antibiotic treatment. Skin biopsy shows poorly differentiated squamous carcinoma cells within dermis and dilated dermal vessels.

Acute paronychia heralding the exacerbation of pemphigus vulgaris.

Acute paronychia, the suppurative inflammation involving the paronychium of the nails, is usually caused by bacterial or fungal infection and has been rarely reported as a presentation of pemphigus vulgaris (PV). We report a woman with PV who presented with suppurative paronychia of multiple fingernails and toenails, which preceded the exacerbation of other mucocutaneous lesions. A biopsy specimen of the paronychium revealed suprabasal vesicles due to acantholysis. Systemic corticosteroids and adjuvant immunosuppressants were effective in treating mucocutaneous lesions as well as nail disease. We conclude that in patients with PV, acute paronychia could be a manifestation of the disease per se, rather than an infectious process. Only the precise diagnosis with adequate immunosuppressive treatment can lead to good control of disease activity.

Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease.

We report a patient with hemoglobin sickle cell-hemoglobin C disease who developed the clinical syndrome of thrombotic thrombocytopenic purpura (TTP) during admission for typical acute pain crisis. The potential for multiorgan involvement secondary to vaso-occlusive crisis complicated the diagnosis and overlapped with the patient's clinical presentation of chronic bone pain and hemolytic anemia. Clinical improvement and normalization of laboratory parameters followed rapidly in response to plasma exchange therapy.

Stresses at the cervical lesion of maxillary premolar--a finite element investigation.

OBJECTIVES: The objective of this study was to use a three-dimensional (3-D) finite element model to investigate normal stress distribution to substantiate the tooth flexure mechanism. The study also compared the changes in the stresses by different occlusal loading sites and directions. METHODS: The 3-D finite element analysis was used. A maxillary premolar was selected to construct the simulation model. The model was constructed step-by-step for convergence and validity. Seven load conditions for various load sites and different directions were simulated to the model. RESULTS: The maximal principal stress and minimal principal stress distributions developed within the structures of seven load conditions were output and their stress distributions on z-plane at the vertical midline were shown. The peak tensile stress of the cervical area for various load conditions were compared and listed. CONCLUSIONS: This study has shown that the presence of tensile stresses in the cervical region of a maxillary premolar by various loading sites and different directions. The results coincided with the stress-induced theory, hence sustaining it. The relationship of the affected factors of leverage to the development of cervical abfraction lesions, was explored.