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The article discusses a study which focuses on breast cancer patients with micrometastases in sentinel lymph nodes (SLN). The study aims to demonstrate the differences between micrometastatic breast cancers with additional metastatic LN and without LN invasion. The study found micrometastases in SLNs in 30 patients, and the incidence of additional LN invasion in micrometastasic SLNs was 24 percent.

The article presents a study of evaluating the diagnostic value of nipple discharge (ND) cytology and galactography in duct pathology. Different values of sensibility and specificity in detecting duct pathology, potential malignant transforming lesions, positive and negative predicative value, and breast cancer are shown for both cytology and galactography. It mentions the evaluation of performance in predicting nipple discharge.

The article discusses the role of chemotherapy in cancer treatment. It states that chemotherapy can have good results as well as adverse side effects such as toxicity and resistance of tumour cells. It cites the results of research and development of locoregional administration techniques using higher concentrations with fewer side effects. It describes the new local cancer chemotherapy method that can revolutionize the management of tumour using the effective microdialysis procedure.

Objective: The aim of this study was to investigate the effects of transdentinal irradiation with different light-emitting diode (LED) parameters on odontoblast-like cells (MDPC-23)., Methods and Materials: Human dentin discs (0.2 mm thick) were obtained, and cells were seeded on their pulp surfaces with complete culture medium (Dulbecco modified Eagle medium). Discs were irradiated from the occlusal surfaces with LED at different wavelengths (450, 630, and 840 nm) and energy densities (0, 4, and 25 J/cm(2)). Cell viability (methyltetrazolium assay), alkaline phosphatase activity (ALP), total protein synthesis (TP), and cell morphology (scanning electron microscopy) were evaluated. Gene expression of collagen type I (Col-I) was analyzed by quantitative polymerase chain reaction (PCR). Data were analyzed by the Mann-Whitney test with a 5% significance level., Results: Higher cell viability (21.8%) occurred when the cells were irradiated with 630 nm LED at 25 J/cm(2). Concerning TP, no statistically significant difference was observed between irradiated and control groups. A significant increase in ALP activity was observed for all tested LED parameters, except for 450 nm at 4 J/cm(2). Quantitative PCR showed a higher expression of Col-I by the cells subjected to infrared LED irradiation at 4 J/cm(2). More attached cells were observed on dentin discs subjected to irradiation at 25 J/cm(2) than at 4 J/cm(2)., Conclusion: The infrared LED irradiation at an energy density of 4 J/cm(2) and red LED at an energy density of 25 J/cm(2) were the most effective parameters for transdentinal photobiomodulation of cultured odontoblast-like cells.

The authors present a case of endometrial adenocarcinoma after endometrial ablation, emphasizing the importance of close surveillance of these patients, patient selection and education. Even patients with none of the risk factors for endometrial cancer or contraindications to endometrial ablation should be checked carefully.

In breast cancer, the correct evaluation of cancer dissemination is essential to establish prognosis and treatment choices. This study analyses the relationship between circulating levels of soluble VCAM-1 and E-selectin and the presence of circulating cancer cells in breast cancer patients. Plasma levels of VCAM-1 and E-selectin were measured by enzyme-linked immunosorbent assay (ELISA). The presence of circulating cancer cells was diagnosed using a RT nested-PCR assay detecting the cancer specific transcript, epidermal growth factor receptor variant III (EGFRvIII) mRNA. Blood samples were collected from 64 patients divided in three groups: group A of 11 women selected for neoadjuvant chemotherapy; group B of 13 women with metastatic disease and group C, with 40 women having completed their treatment at least one year ago and with no evidence of relapse. The mutant transcript was detected in 45.5% of patients from group A, in 61.5% of patients from group B and in none of the group C patients. For both VCAM-1 and E-selectin, plasma levels increased with disease staging and with the presence of EGFRvIII mRNAin peripheral blood. The differences were statistically significant (p < 0.025) when group C was compared with all patients from group B, with patients from group B with EGFRvIII positive results or with all patients with EGFRvIII positive results. Increased plasma levels of VCAM-1 and E-selectin are associated with advanced stage of breast cancer and with the presence of circulating cancer cells. The combined analysis of these parameters may contribute to a more accurate evaluation of cancer dissemination.

Objectives: Retrospective evaluation of the clinical behavior, treatment and prognosis in five cases of primary breast lymphoma., Methods: From 1999 to 2003, five patients with primary breast lymphoma were diagnosed in our department., Results: Primary breast lymphoma (PBL) was diagnosed in five patients, whose median age was 63.4 (41-79) years. In four out of five patients, a diagnosis of lymphoma was made after the evaluation of a palpable breast mass measuring 1.5 to 6 cm. All of them were classified as non-Hodgkin's B cell lymphomas and three of five cases were diffuse large cell lymphomas. All patients were submitted to chemotherapy; in only one patient was surgery performed., Conclusions: A relatively high rate of PBL was observed in our department compared with other oncology centers. Beyond its scarce appearance, PBL is very difficult to distinguish from primary breast carcinoma. Histology remains the major diagnostic tool.

We present a case of a 53-year-old woman who developed an endometrioid adenocarcinoma six years after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), who was on estrogenic-only hormone replacement therapy (HRT).

By means of a questionnaire, sent to the Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the diagnosis of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed in the years 1985, 1990, 1995 and 2000. It was found that the presentation form of breast cancer in 1985 was of palpable tumour in 87% of the cases, whereas in 2000 this situation only corresponded to 54% of the patients, being most of the remaining patients diagnosed by imaging without palpable tumour. In 94% of the patients, the first diagnostic investigation was mammography, associated or not to echography, and the second most frequent investigation was fine-needle aspiration biopsy. The time evolution of the tumour size showed an increasingly earlier diagnosis. Invasive tumours not more than 1 cm represented 13.2% in 1985 and 20.3% in 2000. On the other hand, breast cancers more than 2 cm and not more than 5 cm decreased from 67.2% in 1985 to 40% in 2000. When oncology centres and some large university hospitals (Group A) were compared to the other hospitals (Group B), there were no significant differences between the diagnostic methods, although the sequence of diagnostic methods was different in the hospitals in Group A versus those in Group B. It was observed that in more differentiated hospitals the diagnosis was achieved increasingly earlier along the studied periods, and this situation did not occur in the other hospitals.

By means of a questionnaire sent to Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the treatment of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed by the years 1985, 1990, 1995 and 2000. It was observed that, in terms of surgery, there was an increase in conservative surgery, which was over 40% in 2000, as well as an increase in the average of excised axillary lymph nodes. Progress in the surgical approach was similar both in cancer centres and in large and university hospitals, when compared with the other surveyed hospitals. Also, no differences between these two hospital groups in disease-free survival and overall survival were found. Postoperative radiotherapy was employed in more than 90% of the patients submitted to conservative surgery and adjuvant chemotherapy was used in 39% of all the patients, while tamoxifen as adjuvant treatment was used in 58% of the patients.

Purpose: The aim of this study was to evaluate the diagnostic ability of ultrasound and color Doppler in axillary lymph node metastases of patients with breast cancer., Material and Methods: A prospective study including 55 patients with primitive, invasive, node negative breast cancer who underwent preoperative axillary ultrasound and color Doppler. Doppler and morphologic ultrasound criteria were applied to the identification of axillary lymph node metastases., Results: The imagery study of all 55 patients identified a total of 141 nodes; 44 were considered to be positive according to established criteria. The histological examination of the axillary dissection revealed a total of 989 nodes; 77 out of 989 presented metastases; all invaded nodes belonged to 21 patients. The previous imagiologic study was positive for axillary lymph node metastases in 15 out of these 21 patients. A sensitivity of 71.4%, a specificity of 71.4%, a negative predictive value of 80.6% and a positive predictive value of 60.0% were achieved., Conclusion: The imagery study of the axillary region through ultrasound and color Doppler might be useful in assessing axillary lymph node metastases in patients with breast cancer.

Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination., Patients and Methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks., Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024)., Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status.

The aim of this study was to investigate the efficacy and toxicity of carboplatin given as monotherapy in endometrial adenocarcinoma. Cisplatin is one of the most active drugs in gynaecological cancer types, but at the cost of an associated high toxicity. In this high-risk population of endometrial cancer patients, it is necessary to have chemotherapy regimens with a low toxicity. Patients eligible for this study were those with histologically-confirmed endometrial adenocarcinoma with evidence of recurrent and/or metastatic disease. Carboplatin was administered every 4 weeks as a first- (dose: 400 mg/m(2)) or second- (dose: 300 mg/m(2)) line chemotherapy. Of the 64 patients who entered the trial, 60 were eligible, 53 patients were evaluable for toxicity and 47 for efficacy. A total of 169 cycles of carboplatin was given with a median of 2 cycles per patient (range 1-11 cycles) to a median cumulative dose of 798 mg/m(2) (range 290-3879 mg/m(2)). No grade 4 toxicity or toxic deaths occurred. White Blood Cell (WBC) toxicity grade 3 was noted five times, mainly in the radiotherapy pre-treated patients. Grade 3 non-haematological toxicity consisted mainly of nausea and vomiting (21%). There was a total of eight responses (3 Complete Responses (CR) and 5 Partial Responses (PR) with an overall response rate (ORR) of 13% (95% Confidence Interval (CI) 6-25). No responses occurred in patients treated with prior chemotherapy. In evaluable patients, the ORR in all patients (n=47) and in those receiving first-line chemotherapy (n=33) were, 17% (95% CI 8-31) and 24% (95% CI 11-42), respectively. After a median follow-up of 379 days, the median duration of response was 488 days (range 141-5303 days) with two very long responses in patients with a CR. Carboplatin has a low toxicity and is active in chemotherapy-naive advanced endometrial carcinoma patients. These results lead us to propose its use in association in first-line chemotherapy in recurrent or advanced endometrial carcinoma patients. The choice of the initial dose can be determined according to whether the patients have received prior radiotherapy treatment.

Breast cysts can be separated into two types: Type I cyst with a lining epithelium which shows apocrine metaplasia, and Type II cyst with an epithelium which is markedly attenuated or absent. The risk of subsequent breast cancer among patients with Type I cysts can be up to 4. The standard treatment is fine needle aspiration, but 20% of the cysts recur. Pharmacological treatment has been tried, which reduces size and volume, but has side-effects and a high recurrence rate post-treatment occurs. The objectives of this prospective study were to sclerose the cyst, induce its regression and prevent or reduce recurrence rate, with the administration of a sclerosing solution (Sclerovein) within the cyst post-aspiration. Fifty-seven patients were followed in the study, 37 with Type I cysts and 20 with Type II cysts. At the end of six months all patients with Type II cysts had no detectable cyst. On the other hand, two patients still had a residual Type I cyst. At the end of three years our recurrence rate appears to be less than 2%, with one patient with a possible recurrence. No significant side-effects were observed. The use of Sclerovein is a simple and safe alternative in the treatment of recurring cysts.

Objective: To investigate the clinical activity and toxicity of a combination chemotherapy consisting of cyclophosphamide (C), adriamycin (A) and cisplatin (P) for patients with primary adenocarcinoma of the Fallopian tube having FIGO stage III-IV disease., Methods: The CAP-regimen consisted of cyclophosphamide 600 mg/m2, adriamycin 45 mg/m2, and cisplatin 50 mg/m2 administered intravenously on day one every 28 days., Results: Twenty-four eligible patients with histologically-confirmed Fallopian tube adenocarcinoma were entered in the trial. Fourteen patients had FIGO stage III, and ten had stage IV disease. The median number of CAP cycles was six. Ten patients had a complete and six had a partial response (response rate: 67%, 95% confidence limits: 45-84%). WHO grade III-IV side-effects included haematological toxicity, nausea/vomiting and alopecia. Furthermore, mild signs of cisplatin-related peripheral neurotoxicity were observed. At a median follow-up of 40 months, nine patients were alive and 15 had died due to malignant disease. The median time to progression was 13 months for all patients. The median overall survival was 24 months and the 1-, 3- and 5-year survival and their 95% confidence limits were 73% (54-92%), 25% (4-46%) and 19% (0-38%), respectively., Conclusion: The present data confirm the therapeutic activity of the CAP-regimen in primary Fallopian tube adenocarcinoma. The response rate is moderate and the toxicity profile is acceptable.

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.

The prevalence of human papillomavirus (HPV) genotypes was estimated by the polymerase chain reaction (PCR), in archival paraffin was embedded tissues. The case group consisted of 84 women aged 21-67 years (mean, 40 years) who were referred to the Department of Gynaecology (Oncology Centre, Coimbra) with citopathologically abnormal smears. This group was selected from a population of women who had undergone a screening programme (1990/94) in Central Region of Portugal. All these patients (n = 84) had a colposcopic directed cervical biopsy. HPV detection and typing was performed by the PCR method in the Department of Virology (National Health Care Institute, Lisbon). The prevalence of DNA/HPV found, concerning all epithelial cervical lesions studied and classified as squamous intra-epithelial lesions (SIL) and cervical cancer was 97.8%. On the basis of the data presented in this study, it was estimated that there was a statistically significant prevalence of low risk HPV types (HPV 6/11) in low grade SIL, 83.3%, and a statistically significant prevalence of high risk HPV types (HPV 16,18,31,33,51) in high grade SIL, 58.4%, as well as cervical cancer lesions in 100%. We conclude that there was a statistically significant difference between women with low and high grade SIL for HPV infection, with low and high risk HPV types, respectively. The risk factors for cervical cancer investigated (age at first sexual intercourse, multiple sexual partners, parity, use of oral contraceptives) were not associated to statistically significant differences concerning low grade SIL and high grade SIL. The clinical and therapeutic procedures were evaluated for the same five years (1990/94). It may be concluded that there would be no significant difference in clinical procedure for high grade lesions and cervical cancer, in which the treatment had been frequently radical (cone biopsies, simple or radical hysterectomy) and in which the HPV infection persisted frequently and was associated to high risk types (HPV 16 in 50% of these cases). On the other hand, it may be concluded that HPV detection in cervical biopsies, especially for low grade SIL lesions, which were evaluated in this study with a more conservative procedure (clinical evaluation only, punch biopsies, loop diathermy, CO2 laser vaporisation, cone biopsies), could identify women with high risk HPV types who might be at risk of developing dysplasia and cervical cancer.

Chronic administration of the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats causes hypertension and morphological abnormalities in the heart, consisting mainly of ventricular hypertrophy and foci of necrosis and fibrosis. Since these phenomena have usually been described with high (or moderate) doses of L-NAME, this study was undertaken to evaluate the effects of a low dose of L-NAME on arterial blood pressure, heart weight index, left ventricular weight index, amount of ventricular fibrosis, and cardiomyocyte size. Male Wistar rats received L-NAME (7.5 mg/kg per day) in the drinking water for 2, 4, and 6 months, whereas control animals received tap water alone. At this dose, L-NAME caused 90% inhibition (P<0.001) of brain NO synthase (NOS) activity. The chronic L-NAME treatment caused an approximately 15% reduction in body weight of the animals, and no death was observed. The tail-cuff pressure was markedly (P<0.01) elevated in L-NAME-treated rats. A significant (P<0.05) reduction in both heart weight index (13-20% decrease) and left ventricular weight index (20-34% decrease) at 2, 4, and 6 months of treatment was observed in L-NAME-treated rats. The cardiomyocyte size in subendocardial, subepicardial, and midmyocardial regions of the left ventricles was time-dependently reduced, irrespective of the region studied, as measured at 2 (11% decrease), 4 (28% decrease, P<0.05), and 6 (45% decrease, P<0.05) months of chronic L-NAME treatment. The amount of fibrous tissue was unaltered at 2 and 4 months, but a small (but significant) increase in the amount of fibrous tissue was detected at 6 months (7.1+/-0.2 %, P<0.05) compared to that of control animals (5.9+/-0.2%). Our results show that chronic treatment of rats with a low dose of L-NAME for prolonged periods (up to 6 months) causes arterial hypertension accompanied by significant reductions in heart weight, left ventricular weight indexes, and cardiomyocyte size.

The role of adenosine on regulation of the (Na(+)+K(+))ATPase activity present in the Malpighian tubules isolated from Rhodnius prolixus was investigated. Adenosine decreases the (Na(+)+K(+)) ATPase specific activity by 88%, in a dose-dependent manner, with maximal effect at a concentration of 10(-9) M. This effect was mimicked by N(6)-cyclohexyladenosine (CHA) at 10(-8) M, an agonist for A(1) adenosine receptor, and was reversed by 10(-9) M 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an antagonist for A(1) adenosine receptor. On the other hand, 5'-N-ethyl-carboxamide adenosine (NECA), an agonist for A(2) adenosine receptor, used in the range of 10(-9)-10(-5) M, did not change the (Na(+)+K(+))ATPase specific activity. In the same way, 10(-8) M 3, 7-dimethyl-1-propargylxanthine (DMPX), an antagonist for A(2) adenosine receptor, did not modify the inhibitory effect of adenosine. These data suggest that the inhibitory effect of adenosine on the (Na(+)+K(+))ATPase specific activity present in Malpighian tubules from Rhodnius prolixus is mediated by A(1) adenosine receptor activation. Arch., (Copyright 2000 Wiley-Liss, Inc.)

Molecular biology techniques are increasingly used to study the molecular epidemiology of infectious diseases. Most of these methods are expensive and labor-intensive. The human immunodeficiency virus (HIV) has substantial genomic variation, such that HIVs from different individuals are genetically diverse, although mutation rates differ for distinct regions of the genome. Most studies of HIV linkage and molecular evolution have focused on env or gag regions. We show that heteroduplex mobility analysis of the first exon of the HIV tat gene provides a simple, rapid, inexpensive, and reliable discriminatory tool for the molecular differentiation of shared versus distinct HIV-1 quasispecies when epidemiologic relations need to be defined. tat, as a relatively conserved region, appears to be a better region than the more variable env region to establish HIV-1 epidemiological linkages.

The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.

This study concerns the evaluation of epidemiologic, clinical and laboratory parameters and the comparison of the multiple parameters between benign and malignant tumors of the ovary to establish significant criteria allowing a Malignant Risk Index to be defined. The incidence of ovarian cancer was higher among post-menopausal women with no use of oral contraceptives. There was no correlation between sterility, infertility or nulliparity and ovarian cancer. The age at menarche, menopause or first term delivery showed no influence on the risk of ovarian cancer. The Authors verified significant differences (p < 0.001) in the levels of serum CA 125 between patients with benign ovarian tumors and patients with ovarian cancer. Those differences showed high sensitivity and specificity. Ultrasonographic criteria were difficult to interpret because of their subjectivity. However, there were significant differences concerning the size of the tumors, the bilaterality, the solid component and ascites; all these criteria were more frequent among malignant masses. It is imperative to define a high confidence degree Malignant Risk Index for ovarian tumors allowing the establishment of screening strategies applicable to risk populations.

The clinical, transvaginal sonography and colour flow mapping of one patient with placental site trophoblastic tumour is presented. Colour Doppler documented a marked increase in uterine vascularity, characterised by low diastolic flow suggestive of low resistance blood flow, without regression after completion of apparently successful chemotherapy, when negative beta-hCG plasma levels were obtained. Surgical treatment was based upon our experience with colour Doppler assessment of gestational trophoblastic tumours and a review of the literature. This case suggests that TV-CDS, performed serially, is very useful in monitoring patients during chemotherapy and in detecting residual tumour, and should greatly increase the accurancy of diagnosis of PSTT.