Predictors of higher number of stages in Mohs micrographic surgery for the treatment of squamous cell carcinoma of the head

BACKGROUND - Squamous cell carcinomas of the skin of the bead are better treated with Mobs micrographic surgery which has the lowest recurrence rates and allows spare normal tissue. There are some characteristics of squamous cell carcinoma that can be related to a higher number of surgical stages. OBJECTIVE - To study characteristic of head squamous cell carcinoma that predicts a higher number of Mohs surgical stages. METHODS - A retrospective analysis of 51 squamous cell carcinomas of the bead treated with Mobs surgery was performed to determine risk factors for a higher number of surgical stages. The characteristics analyzed were clinical limits, morphology, recurrence, histological differentiation and size and compared to the number of surgical stages. The analysis was performed by Fisher`s exact test and multivariate logistic regression. RESULTS - The recurrent squamous cell carcinomas showed a tendency for a higher number of stages (p=0,081). The Odds Ratio for a higher number of Mobs stages was three for inaccurate limits; although not statistically significant, it corroborates clinical and previous publication. CONCLUSION - Clinical characteristics of squamous cell carcinoma as recurrence and inaccurate limits would not predict, but could indicate tendency of a higher number of Mobs micrographic surgery stages.

Severe Posterior Epistaxis-Endoscopic Surgical Anatomy

Objective: To describe the anatomy of the sphenopalatine foramen (SPF) region and possible anatomical variations. Study Design: Prospective study accomplished from September, 2006, to January, 2007. Methods: The sphenopalatine foramen (SPF) of 61 cadavers were carefully dissected. Presence of the ethmoidal crest, location of sphenopalatine and accessory foramens, and the number of arterial branches emerging through foramens were observed. Data were analyzed in relation to gender, racial group, and symmetry of the cadaver. Prediction of the presence of accessory foramen was evaluated. Results: Mixed race cadavers prevailed in 122 nasal fossae dissected (75% males). Ethmoidal crest was present in 100% of the cadavers, being anterior to the SPF in 98.4% of the cases. The most frequent SPF location was the transition of the middle and superior meatus (86.9%). Mean distance from the SPF and accessory foramen to anterior nasal spine was 6.6 cm and 6.7 cm, respectively. Accessory foramen was present in 9.83% of the cases. A single arterial stem emerged through the SPF in 67.2% of the cases, and 100% through accessory foramens. The prevalence analyses showed no differences that were statistically significant (P > 0.05) between gender and racial group. The symmetry analyses showed a strong conformity (P < 0.01) between nasal fossae in relation to the SPF location. There was no statistically significant conformity between nasal fossae and accessory foramen (P = 0.53). None of the variables of interest presents any statistically significant (P > 0.05) association with the presence of the accessory foramen. Conclusions: There are anatomical variations in the lateral nose wall that should be considered for successful endoscopic surgical treatment of severe epistaxis.

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy

Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

Negative Anti-C1q Antibody Titers May Influence Therapeutic Decisions and Reduce the Number of Renal Biopsies in Systemic Lupus Erythematosus

In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE. Copyright (C) 2011 S. Karger AG, Basel

Decreased recent thymus emigrant number in rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

Objectives To determine TCR excision circle (TREC) levels, a marker of recent thymic emigrants, in the peripheral lymphocyte pool of rheumatoid factor-negative (RF circle divide) polyarticular juvenile idiopathic arthritis (JIA) children. Materials and methods We studied TREC levels in peripheral blood mononuclear cells (PBMC) in 30 RF circle divide polyarticular JIA children with active disease and in 30 age- and gender-matched healthy controls. Signal-joint TREC concentration was determined by real-time quantitative-PCR as the number of TREC copies/mu g PBMC DNA gauged by a standard curve with known number of TREC-containing plasmids. Results TREC levels in PBMC were significantly lower in JIA (4.90 +/- 3.86 x 10(4) TRECs/mu g DNA) as compared to controls (10.45 +/- 8.45 x 10(4) TRECs/mu g DNA, p=0.001). There was an inverse correlation between age and TREC levels in healthy children (r=-0.438, p=0.016) but not in JIA. No clinical association was observed between TREC levels and disease activity and use of oral steroids and methotrexate. Conclusions The finding of decreased PBMC TREC levels in RF circle divide polyarticular JIA children is consistent with a low proportion of recent thymus emigrants. This may interfere with the equilibrium between populations of polyclonal and naive T cells versus oligoclonal memory auto-reactive T cells and, therefore, may hinder the maintenance of immune tolerance in this disease.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

The effect of the number of biopsy cores on the concordance between prostate biopsy and prostatectomy Gleason score - A prostate volume-controlled study

Context.-Studies analyzing the concordance of biopsy and radical prostatectomy (RP) Gleason scores have limitations. Some included 2 or more centers, used historical controls from the early prostate specific antigen era or lacked a clear definition of the biopsy schemes. Furthermore, most did not control the results for prostate volume. Objective.-To confirm whether prediction of RP Gleason score can be optimized by taking more biopsy cores in a contemporary series of patients, with pathologic samples analyzed by the same pathologist, and controlling these results for prostate volume. Design.-The study comprised a retrospective case-control analysis of 393 patients with prostate cancer treated with RP. Patients were divided into 3 groups: those in group 1 underwent a 6-core biopsy; group 2, an 8-core biopsy; and group 3, a 10 or more-core biopsy. Concordance rates between biopsy and RP Gleason scores, as well as the rates of undergrading and overgrading, were determined for each biopsy scheme. Results.-Concordance rates were 60.9%, 58.3%, and 64.6% for patients from groups 1, 2, and 3, respectively (P = .18). When we analyzed patients with prostate volumes of less than 50 cm(3), concordance rates were 58.3%, 58.3%, and 65.1% for each group, respectively (P = .03). Among patients with prostate volumes of 50 cm3 or more, concordance rates were 70%, 58.1%, and 63.6%, respectively (P = .66). Conclusions.-Taking 10 or more cores can improve the prediction of RP Gleason score in patients with prostate volumes of less than 50 cm3. For patients with prostate volumes of 50 cm3 or more, increasing the biopsy cores to 10 or more did not improve prediction of RP Gleason score.

Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty

Background: A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective: To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. Subjects and methods: The GHSR coding region was directly sequenced in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults, and in 197 children with normal stature. The pharmacological consequences of GHSR non-synonymous variations were established using in vitro cell-based assays. Results: Five different heterozygous point variations in GHSR were identified (c.-6 G>C, c.251G>T (p.Ser84Ile), c.505G>A (p.Ala169Thr), c.545 T>C (p.Val182Ala), and c.1072G>A (p.Ala358Thr)), all in patients with CDGP. Neither these allelic variants nor any other mutations were found in 694 alleles from controls. Functional studies revealed that two of these variations (p.Ser84Ile and p. Val182Ala) result in a decrease in basal activity that was in part explained by a reduction in cell surface expression. The p.Ser84Ile mutation was also associated with a defect in ghrelin potency. These mutations were identified in two female patients with CDGP (at the age of 13 years, their height SDS were -2.4 and -2.3). Both patients had normal progression of puberty and reached normal adult height (height SDS of -0.7 and -1.4) without treatment. Conclusion: This is the first report of GHSR mutations in patients with CDGP. Our data raise the intriguing possibility that abnormalities in ghrelin receptor function may influence the phenotype of individuals with CDGP.

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Variations of Jitter and Shimmer Among Women in Menacme and Postmenopausal Women

The objective of the study was to analyze comparatively the jitter and shimmer values of spoken voice among women in menacme and menopausal women using or not hormonal replacement therapy (HRT). Forty-five women were studied, divided into the following groups: Control Group (CG), 15 women aged 20-40 years with regular menstrual cycles who did not take hormonal contraceptives, Treated Group (TG), 15 women aged 45-60 years with at least 2 years of menopause, under continuous HRT with I mg estradiol valerate + 90 mu g norgestimate per day for at least 6 months; Untreated Group (UG), 15 women aged 45-60 years with at least 2 years of menopause who did not use HRT. Mean age was 30.3, 54.5, and 56.5 years for CG, TG, and UG, respectively. All subjects were submitted to acoustic analysis of jitter and shimmer for the sustained vowels /e/ and /i/. Mean jitter values were 0.56%, 0.64%, and 0.56% for the vowel /e/ and 0.88%, 0.79%, and 0.68% for the vowel /i/ for CG, TG, and UG, respectively. Mean shimmer values were 4.17%, 4.38%, and 4.77% for the vowel /e/ and 5.19%, 4.59%, and 5.37% for the vowel /i/ for CG, TG, and UG, respectively. There were no significant differences between the groups studied. The results obtained here by the methodology used suggest that there were no significant differences in jitter and shimmer when we assessed the sustained vowels /i/ and /e/ between menopausal women using or not HRT or between young and menopausal women treated or not.

Number of expressed cancer/testis antigens identifies focal adhesion pathway genes as possible targets for multiple myeloma therapy

Considering that the importance of cancer/testis (CT) antigens in multiple myeloma (MM) biology is still under investigation, the present study aimed to: (1) identify genes differentially expressed in MM using microarray analysis of plasma cell samples, separated according to the number of expressed CTs; (2) examine possible pathways related to MM pathogenesis; (3) validate the expression of candidate genes by quantitative real-time PCR (RQ-PCR). Three samples predominantly positive (>6 expressed), including the U266 cell line, and three samples predominantly negative (0 or 1 expressed CT for the 13 analyzed CT antigens), were submitted for microarray analysis. Validation by RQ-PCR from 24 MM samples showed that the ITGAS gene was downregulated in predominantly positive (>6 expressed CTs, p = 0.0030) and in tumor versus normal plasma cells (p = 0.0182). The RhoD gene was overexpressed in tumor plasma cells when compared to normal plasma cells (p = 0.0339). Results of the microarray analysis corroborate the hypothesis that MM could be separated into predominantly positive and predominantly negative expression. The differential expression of ITGA5 and RhoD suggests disruption of the focal adhesion pathway in MM and offers a new target field to be explored in this disease.

Influence of dentin on pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination

The aims of endodontic treatment in cases of apical periodontitis are to reduce as much as possible the number of microorganisms inside the root canal system and to inactivate toxins produced by them. Most of the times, these objectives are not achieved solely by chemomechanical preparation, and intracanal dressing may be necessary. In these cases, calcium hydroxide is used as a root canal dressing due to its well-known and recognized antimicrobial activity. Chlorhexidine has a wide spectrum of antimicrobial activity and its association with calcium hydroxide has been recommended in an attempt to amplify antimicrobial effects of calcium hydroxide. It is also known that dentin exerts a buffering effect under wide pH variations, and may be responsible for decreasing the antimicrobial activity of drugs inside the root canal. The objectives of this study were to assess the pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination, as well as the influence of dentin on the pH of these compounds. Dentin powder was obtained from bovine teeth and added as 1.8% to the volume of the medications. All substances were individually stored in plastic flasks, in triplicate. A pH meter was used at five different moments to assess pH in viscous medium: immediately after preparation and after 24 h, and 7, 14, and 21 days. Results were analyzed by paired Student`s t-test. Statistically significant differences were observed in the 2% chlorhexidine gel group alone or associated with calcium hydroxide and added of dentin powder (P < 0.05). Mean pH values indicated the influence of dentin powder because of a significant increase in pH. Calcium hydroxide with propylene glycol as the vehicle always showed high pH, demonstrating that this compound was not affected by the presence of dentin.

Daily variations in human plasma fluoride concentrations

This study investigated the variations in human plasma fluoride concentrations ([F]) and sought to determine the causes. Five subjects (27-33 years old) received a low-F diet during the 5 days of the study. Plasma samples and urine were collected every 3 h from 8 a.m. to 8 p.m. F, PTH, Ca and P were analyzed with the electrode, by chemiluminescence, AAS and colorimetry, respectively. A trend for the plasma [F] was found. The peak [F], 0.55 +/- 0.11 mu mol L(-1), occurred at 11 a.m. and the lowest [F], 0.50 +/- 0.06 mu mol L(-1) occurred between 5 and 8 p.m. Plasma [F] were positively correlated with urinary F excretion rates and with serum PTH levels, but not with the Ca or P levels. Serum PTH levels were positively correlated with urinary F excretion rates and negatively correlated with plasma Ca. The results suggest that the renal system seems to control the daily fluctuations in plasma [F]. (c) 2008 Elsevier B.V. All rights reserved.

Functional polymorphisms in the promoter of the matrix metalloproteinase-9 (MMP-9) gene are not linked with significant plasma MMP-9 variations in healthy subjects

Background: Matrix metalloproteinase-9 (MMP-9) is involved in the degradation of the extracellular matrix during physiological and pathological processes. Two functional polymorphisms [C(-1562)T and microsatellite (CA)(13-25)] in the promoter region of the MMP-9 gene have been associated with several diseases. The aim of this study was to examine whether these MMP-9 polymorphisms and haplotypes are linked with plasma MMP-9 variations in healthy subjects. Methods: We studied 177 healthy male white volunteers (age range 20-55 years) who were non-smokers and not taking any medication. Genomic DNA was extracted from whole blood and genotypes for the C(-1562)T and the microsatellite (CA)(n) polymorphisms were determined. MMP-9 levels were measured in plasma samples by gelatin zymography. Results: The frequency of the alleles C and T for the C(-1562)T polymorphism were 90% and 10%, respectively. The frequency of the alleles with less than 21 CA repeats Q and with 21 repeats or higher (H) were 47% and 53%, respectively. We found no differences in plasma MMP-9 levels among the genotype groups or among different haplotypes (all p > 0.05). Conclusions: These findings suggest that functional polymorphisms in the promoter of the MMP-9 gene are not linked with significant plasma MMP-9 variations in healthy subjects.

Alpha-oestrogen and progestin receptor expression in the hypothalamus and preoptic area dopaminergic neurones during oestrous in cycling rats

A secretory surge of prolactin occurs on the afternoon of oestrous in cycling rats. Although prolactin is regulated by ovarian steroids, plasma oestradiol and progesterone levels do not vary during oestrous. Because prolactin release is tonically inhibited by hypothalamic dopamine and modulated by dopamine transmission in the preoptic area (POA), the present study aimed to evaluate whether oestrogen receptor (ER)-alpha and progestin receptor (PR) expression in the dopaminergic neurones of arcuate (ARC), periventricular, anteroventral periventricular (AVPe) and ventromedial preoptic (VMPO) nuclei changes during the day of oestrous. Cycling rats were perfused every 2 h from 10-20 h on oestrous. Brain sections were double-labelled to ER alpha or PR and tyrosine hydroxylase (TH). The number of TH-immunoreactive (ir) neurones did not vary significantly in any area evaluated. ER alpha expression in TH-ir neurones increased at 14 and 16 h in the rostral-ARC and dorsomedial-ARC, 14 h in the caudal-ARC and 16 h in the VMPO, whereas it was unaltered in the ventrolateral-ARC, periventricular and AVPe. PR expression in TH-ir neurones of the periventricular and rostral, dorsomedial, ventrolateral and caudal-ARC decreased transitorily during the afternoon, showing the lowest levels between 14 and 16 h; but it did not vary in the AVPe and VMPO. Plasma oestradiol and progesterone concentrations were low and unaltered during oestrous, indicating that the changes in receptors expression were probably not due to variation in ligand levels. Thus, our data suggest that variations in ER alpha and PR expression may promote changes in the activity of medial basal hypothalamus and POA dopaminergic neurones, even under unaltered secretion of ovarian steroids, which could facilitate the occurrence and modulate the magnitude of the prolactin surge on oestrous.