Cardiovascular adverse effects associated with the use of anti-HER2 in breast cancer treatment.

Background: Cancer represents an important public health problem with increasing incidence, prevalence, and mortality, affecting the entire Western population, especially in developed and developing countries. The use of monoclonal antibodies has revolutionized the treatment of cancer, but this treatment can cause adverse cardiovascular effects (AE). Objective: The objective of this paper is to identify and classify AE in breast cancer patients in the use of Trastuzumab in two health institutions. Methods: Retrospective study of medical records of patients with breast cancer Her 2+ submitted the therapy with trastuzumab in early and advanced stage of the disease. Review conducted in a university hospital and a private clinic, both located in Rio de Janeiro State, Brazil. Results: Cardiovascular events were late for trastuzumab, with predominance of moderate reactions. There was a predominance of dyspnea, increased blood pressure, fatigue and reduced left ventricular ejection. Conclusion: The results resemble similarities in the pattern of the institutions' reactions. Identify possible AE and know the toxicity profile of trastuzumab can contribute to a safer therapy.

A novel evaluation method for Ki-67 immunostaining in paraffin-embedded tissues.

The Ki-67 labeling index is traditionally used to investigate tumor aggressiveness. However, no diagnostic or prognostic value has been associated to the heterogeneous pattern of nuclear positivity. The aims of this study were to develop a classification for the patterns of Ki-67-positive nuclei; to search scientific evidence for the Ki-67 expression and location throughout the cell cycle; and to develop a protocol to apply the classification of patterns of Ki-67-positive nuclei in squamous epithelium with different proliferative activities. Based on empirical observation of paraffin sections submitted to immunohistochemistry for the determination of Ki-67 labeling index and literature review about Ki-67 expression, we created a classification of the patterns of nuclear positivity (NP1, NP2, NP3, NP4, and mitosis). A semi-automatic protocol was developed to identify and quantify the Ki-67 immunostaining patterns in target tissues. Two observers evaluated 7000 nuclei twice to test the intraobserver reliability, and six evaluated 1000 nuclei to the interobserver evaluation. The results showed that the immunohistochemical patterns of Ki-67 are similar in the tumoral and non-tumoral epithelium and were classified without difficulty. There was a high intraobserver reliability (Spearman correlation coefficient > 0.9) and moderate interobserver agreement (k = 0.523). Statistical analysis showed that non-malignant epithelial specimens presented a higher number of NP1 (geographic tongue = 83.8 ± 21.8; no lesion = 107.6 ± 52.7; and mild dysplasia = 86.6 ± 25.8) when compared to carcinoma in Situ (46.8 ± 34.8) and invasive carcinoma (72.6 ± 37.9). The statistical evaluation showed significant difference (p < 0.05). Thus, we propose a new way to evaluate Ki-67, where the pattern of its expression may be associated with the dynamics of the cell cycle. Future proof of this association will validate the use of the classification for its possible impact on cancer prognosis and guidance on personalized therapy.

Computerized Evaluation of the Immunoexpression of Ki-67 Protein in Odontogenic Keratocyst and Dentigerous Cyst.

Evaluation and comparison of odontogenic keratocysts and detigerous cysts immunoexpression and immunostaining intensities of Ki-67 antigen by assessing the whole extent of the epithelium (all epithelium layers in combination) and each layer individually. Ki-67 immunoexpression was evaluated in 15 odontogenic keratocysts and 6 dentigerous cysts using automated methods and the Aperio Technologies Inc. computer system. No statistically significant differences were observed in immunoexpression nor in immunostaining intensities between both lesions. Also, no statistically significant differences were found between odontogenic keratocysts from maxilla versus mandible nor primary versus recurrent. However, odontogenic keratocyst showed a significantly higher cellular proliferation index in the suprabasal layers compared to the basal layer. Assessment of the cellular proliferation index through a computerized system enabled the evaluation of all epithelial tissue without field selection. The increased Ki-67 immunoexpression in suprabasal layers of odontogenic keratocyst suggests a different biological behavior and more aggressive proliferation potential when compared to dentigerous cyst. The same result was found in recurrent odontogenic keratocysts when compared with primary ones. The odontogenic keratocysts of the maxilla and mandible have similar Ki-67 immunoexpression. The evaluation of cellular proliferation only by immunohistochemical analysis with Ki-67 antigen does not provide enough data to elucidate the biological behavior of odontogenic keratocyst.

Effect of Citric Acid and Ethylenediaminetetraacetic Acid on the Surface Morphology of Young and Old Root Dentin.

INTRODUCTION: The aim of this in vitro study was to evaluate the effect of 10% citric acid and 17% ethylenediaminetetraacetic acid (EDTA) irrigating solutions on the surface morphology of young and old root dentin by determining the number and diameter of dentinal tubules using scanning electron microscopy (SEM). METHODS AND MATERIALS: Fifty healthy human teeth collected from young (≤30 years) and old (≥60 years) individuals (n=25) were first prepared with a Largo bur #2 to produce smear layer on the root canal surface. Subsequently, the crowns and the root middle and apical thirds were sectioned and removed, and the cervical thirds were sectioned vertically in the buccal-lingual direction into two equal halves. The obtained samples were then immersed in 2.5% sodium hypochlorite for 30 min and randomly separated into two treatment groups for each age group. In each age group, ten samples were selected as controls and did not receive any type of treatment. The rest of the specimens were then rinsed, dried and treated for 4 min with 10% citric acid or 17% EDTA. The samples were then assessed with SEM regarding the number and diameter of dentinal tubules. All data were assessed using Student's t-test. The level of significance was set at 0.05. RESULTS: Regardless of the type of treatment, no significant differences were observed in the number of open tubules between the young and old root dentin (P>0.05). Nonetheless, the diameter of the tubules in the old root dentin was larger when 17% EDTA was used (P<0.05). Both, young and old root dentin did not differ with the 10% citric acid treatment (P>0.05). CONCLUSION: The results showed that 17% EDTA treatment induced a significant demineralization in old root dentin.

Epidemiological, clinical and laboratorial profile of renal amyloidosis: a 12-year retrospective study of 37 cases.

BACKGROUND: Renal amyloidosis is one of the main differential diagnoses in the investigation of nephrotic proteinuria in adults, especially elderly patients. OBJECTIVES: The aim of this article is to contribute to international research with epidemiologic data of renal amyloidosis, given the lack of uniformity described in the literature. PATIENTS AND METHODS: A retrospective study of 37 cases of renal amyloidosis diagnosed by kidney biopsy, between 2000 and 2011, considering epidemiological, clinical and laboratory data. RESULTS: Subjects aged between 32 and 80 years. Of the 37 cases, 21 (56.8%) were diagnosed as non-light chain (non-AL) renal amyloidosis and 16 (43.2%) as light chain amyloidosis (AL). There was seen an increase in number of both AL and non-AL cases, with a slight predominance in non-AL. The mean 24-hour proteinuria was 5839.0 mg/day. Hematuria was present in 75% of patients. Hypertension was reported in 34% of patients. Acute renal failure, occurred in about 10% of patients, and chronic loss of renal function was present in about 5% at diagnosis. CONCLUSIONS: Renal amyloidosis is a disease of increasing incidence. The forms of clinical presentation proved to be variable, but the presence of proteinuria or nephrotic syndrome in elderly patients should always prompt the suspicion of renal amyloidosis and is a formal indication of renal biopsy.

A randomized controlled clinical trial to evaluate blood pressure changes in patients undergoing extraction under local anesthesia with vasopressor use.

The control of hypertensive patients' blood pressure and heart rate using vasoconstrictors during surgical procedures under anesthesia is still a major concern in everyday surgical practice. This clinical trial aimed to evaluate the variation of blood pressure and heart rate in nonhypertensive and controlled hypertensive voluntary subjects undergoing oral surgery under local anesthesia with lidocaine hydrochloride and epinephrine at 1:100,000 (Alphacaine; DFL, Brazil), performed in the Oral Surgery Department, Dentistry School, Fluminense Federal University. In total, 25 voluntary subjects were divided into 2 groups: nonhypertensive (n = 15) and controlled hypertensives (n = 10). Blood pressure and heart rate were measured at 4 different times: T0, in the waiting room; T1, after placement of the surgical drapes; T2, 10 minutes after anesthesia injection; and T3, at the end of the surgical procedure. A statistically significant difference (P < 0.05) between the groups was found at times T0 and T2 for the systolic pressure but only at time T0 for the diastolic pressure. The assessment of the heart rate of both groups showed a statistically significant difference (P < 0.05) at time T1. An analysis of the employed anesthetic volume indicated no statistically significant difference (P > 0.05) between the amount administered to nonhypertensive and hypertensive subjects. It was concluded that the local anesthetics studied could safely be used in controlled hypertensive and nonhypertensive patients in compliance with the maximum recommended doses.

Odontogenic tumors: a retrospective study of four Brazilian diagnostic pathology centers.

OBJECTIVE: This article presents the results of a retrospective study of the frequency and classification of odontogenic tumors recorded at four centers of diagnostic pathology in Rio de Janeiro, Brazil. STUDY DESIGN: All medical records and microscopic slides of odontogenic tumor specimens for the years 1997 to 2007 were retrieved from the files of four services of diagnostic pathology in Rio de Janeiro City. Diagnoses were re-evaluated and the tumors classified according to the latest (2005) World Health Organization Classification of Tumors. RESULTS: A total of 201 odontogenic tumors were found among 15,758 oral biopsies (1.3%). The frequencies of these tumors at the four centers ranged from 0.5% at the National Cancer Institute to 3.3% in a private laboratory. Chi-square analysis revealed statistically significant differences (p<0.05) between the proportions of odontogenic tumors in the studied centers. Of these, 94.5% were benign and 5.5% were malignant. Keratocystic odontogenic tumor (32.3%) was the most frequent lesion, followed by ameloblastoma (29.8%) and odontoma (18.4%). CONCLUSIONS: Odontogenic tumors are uncommon in Brazil. Different pathology laboratories reported divergent frequencies of odontogenic tumors, which may reflect institutional specializations and the patient populations served.

Evaluation of inflammatory response of EDTA, EDTA-T, and citric acid in animal model.

INTRODUCTION: The biocompatibility of chelating agents and organic acids have been explained by a variety of methods, and suggestions for use have been based more on clinical observations and physicochemical properties than on biological aspects. The present study aimed to evaluate the inflammatory response of 17% EDTA, 17% EDTA-T, and 10% citric acid in bony defect created in rat jaws. METHODS: Mandibular through and through critical size defects were created bilaterally in 60 rats. Fibrinol (Baldacchi SA, São Paulo, Brazil), a cube-shaped compound of absorbable bovine fibrin foam and sodium chloride, was used as a carrier of the substances. One side had received Fibrinol (control), whereas the opposite side had received Fibrinol soaked with each substance on the 1st, on the 7th, on the 14th, and on the 28th day (n=5 for each day). Hemijaws were prepared for light microscopy, and samples were stained with hematoxylin and eosin. Digitized images were analyzed with a morphometric software (ImageJ; National Institute of Mental Health, Bethesda, MD). to obtain the number of inflammatory cells per area. Comparisons were performed by using the Kruskal-Wallis test (p=0.05). RESULTS: For all days, 10% citric acid and 17% EDTA-T showed, respectively, the lowest and highest number of inflammatory cells per area. All tested substances and controls showed the highest inflammatory cell response on the 14th day. CONCLUSION: Among the tested substances, 10% citric acid proved to be the less aggressive tested solution at 14 days. At 28 days, all solutions were similar, but EDTA-T kept showing the higher number of inflammatory cells.

The influence of medication on salivary flow of the elderly: preliminary study.

OBJECTIVE: This study was to evaluate the influence of medications on unstimulated and stimulated salivary flow in elderly men and women. BACKGROUND: Several diseases and conditions are associated with decreasing salivary flow. Medications can be risk factors for hyposalivation due to the effect particular drug categories. METHODS: Seventy-five elderly of both gender (sixty years old or over) from the Geriatric Dental Clinic at the Federal Fluminense University Dental School, were interviewed about their health status and chronic use of medication. After the interview, unstimulated and stimulated saliva were collected from each subject. The collection time was five minutes, and the flow rate was calculated as ml/min. RESULTS: The mean unstimulated salivary flow was 0.25 ml/min for women and 0.30 ml/min for men, while the mean for stimulated salivary flow was 1.23 ml/min for women and 1.31 ml/min for men, without both differences being non-significant (p > 0.05). The difference between the mean production of unstimulated and stimulated salivary flow was statistically significant, regardless of gender (p < 0.01). A significant reduction of stimulated salivary flow was observed with the usage of cardiovascular agents (p < 0.05). CONCLUSION: Drugs used in cardiovascular disease influence the flow of stimulated saliva.

Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma.

The aims of this study were to assess the expression levels of three proteins involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship with clinicopathologic features and survival in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to evaluate protein expression in 53 primary OSCCs treated by radical surgery with free margins at a single institution in 1999. Histologic specimens were graded and analyzed for perineural invasion, lymphocytic infiltrate, and pattern of invasion. Digital image analysis was performed to quantify immunostaining. Survival was analyzed using the Kaplan-Meier method and Cox's proportional hazard model. Cancer-specific 5-year survival (CSS) was 61% (56% overall survival (OS), and 51% disease-free interval (DFI)). Kaplan-Meier analysis identified pathologic stage (p=0.0007, log-rank test, OS), negative nodes status (pN) (p<0.0001, log-rank test, OS), presence of lymphocytic infiltrate (p=0.0084, log-rank test, OS), and high Bax expression (p=0.025, log-rank test, OS) to each be associated with both better OS and CSS. Tongue tumors (p=0.0179, log-rank test), worst pattern of invasion (p=0.0293, log-rank test), lack of lymphocytic infiltrate (p=0.0328, log-rank test), perineural invasion (p=0.0448, log-rank test), poorly differentiated tumors (p=0.0318, log-rank test), and low Bcl-X expression (p=0.044, log-rank test) were all associated with a low DFI. Cox regression found pN, lymphocytic infiltrate, and Bax expression to be independent prognostic factors for OS and CSS, whereas lymphocytic response and tongue tumors were predictors of DFI. Bcl-2 expression emerged as an independent marker of favorable CSS. Lymphocytic infiltrate was the most meaningful histopathologic parameter in survival analysis, whereas expression of Bcl-2 family members seems to be an important marker of a favorable prognosis in OSCC.