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The purpose of this study was to evaluate the effect of the resting period on hematological and copper-zinc-dependent antioxidant indices in Brazilian elite judo athletes (n = 7). Venous blood samples were collected after 24-h and 5-d periods of resting following a competition, with an interval of 30 d between collections. Two months prior to and during the study, each athlete received an individualized adequate diet. Body composition was determined at both study periods. The following were analyzed: in whole blood, hemoglobin, hematocrit, red cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width, and white cell count; in plasma, zinc, copper, iron, ceruloplasmin, and total iron-binding capacity; in erythrocytes, metallothionein, copper/zinc superoxide dismutase, and osmotic fragility. Dietary intake and body composition did not affect the biochemical measurements. A significant reduction in ceruloplasmin and superoxide dismutase activity was found after 5 d compared to 24 h of resting. A significant correlation between erythrocyte metallothionein and red cell distribution width was observed after 24 h of resting (r = -0.83, p = 0.02), whereas positive correlations of metallothionein with hemoglobin, red cell count, and mean corpuscular hemoglobin concentration were observed after 5 d of resting (r >/= 0.76, p

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.

There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cancer.

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.

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.

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).

Background: Protease inhibitors (PI) are an important HIV-1 treatment tool. The HIV-1 genetic diversity as a result of antiretroviral exposure is a potential barrier to successful antiretroviral therapy., Objectives: To describe the impact of the selective pressure of the PI Indinavir in the protease region of the pol gene of HIV-1., Study Design: We have examined the extent of protease sequence heterogeneity in previously antiretroviral drug naive HIV-1 infected individuals receiving Indinavir as monotherapy for at least 48 weeks., Results: Analysis based on the consensus of this group of sequences showed regions with higher and lower polymorphism. The degree of genetic variation was greater in regions less critical for the structure and function of the enzyme. To investigate the selective pressure imposed by drug therapy, we have analyzed the rate of synonymous (ds) and nonsynonymous (dn) substitutions. The three critical regions for enzyme activity showed ds/dn ratio >1. whereas other regions had ds/dn ratio <1. The detected amino acid mutations had a trend to be conservative, thus maintaining the physical chemical amino acid characteristics. Phylogenetic analysis established the presence of subtype B (n=38), subtype F (n=9), and B/F recombinants within the protease region of pol gene (n=3). More prevalent detected mutations, thought to contribute to antiretroviral resistance, were L63P (42%), L10I (35%), M36I (30%), V82A/T/F (26%)., Conclusions: A great deal of predicted cross-resistance between PIs was observed. Out of the 50 individuals, 34% were considered to have major mutations to Indinavir, and 66% had minor or no mutations to Indinavir. Viral loads were significantly higher among patients with major mutations, compared with patients minor/no mutations, although no differences in the CD4 counts were found. The viral load at baseline and nadir (week 4) was able to predict the group of individuals with greater chances of selecting drug resistance related mutations.

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.

The effects of propranolol and atenolol were investigated on arterial hypertension, cardiomyocyte hypertrophy, and ventricular ischaemic lesions induced by an 8-week treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/rat per day) in Wistar rats. Propranolol and atenolol (30 mg/rat per day each) were given in the drinking water concomitantly to L-NAME. Treatment with L-NAME induced marked arterial hypertension and cardiomyocyte hypertrophy, both of which were significantly reduced by propranolol and atenolol. A marked repairing fibrosis was also observed in L-NAME-treated rats and this was significantly attenuated in animals receiving the beta-blockers. In L-NAME group, 33% mortality was observed, whereas all the animals from the other groups survived. Our study demonstrates that propranolol and atenolol reduce arterial hypertension, cardiomyocyte hypertrophy and myocardial fibrosis induced by L-NAME, suggesting that beta-blockers are of beneficial value in treatment of vascular and cardiac alterations caused by chronic nitric oxide deficiency.

Objective: To corroborate the validity of the recently developed sensitive/less sensitive (S/LS) dual enzyme immunoassay (EIA) strategy for the detection of recently infected individuals and to genetically analyze recently transmitted strains of HIV-1 in a US blood donor population., Design: The S/LS EIA strategy was used to identify 33 recently infected subjects among 281 enrolled HIV-1 seropositive blood donors (from a total of 410 HIV-1 infected subjects identified from 5 230 463 blood donations screened by participating US blood centers in 1995-1996)., Methods: We analysed three host response and viral characteristics were associated with recent HIV-1 infection: rapidly increasing EIA optical density (OD) values, genetically homogeneous env gene quasispecies, and putative non-syncytium inducing env V3 loop sequences. The drug resistance genotypes of the recently transmitted strains were determined by DNA sequencing., Results: Increasing EIA OD values, clonal HIV-1 quasispecies and V3 loop sequences with inferred NSI phenotypes were generally detected in LS EIA non-reactive samples. Thirty-two subtype B and one CRF02&#95;AG recombinant HIV-1 were detected. Genetic evidence for drug resistance to zidovudine (K70R) and non-nucleoside analog reverse transcriptase inhibitors (V108I) was detected in one strain each, and three other strains showed the presence of accessory protease inhibitor resistance mutations., Conclusions: Immunologic and virologic results further substantiate the validity of the S/LS EIA strategy for the detection of recent infections and illustrate its use for targeting molecular and epidemiological investigations to incident cases identified from large cross-sectional screening programs, rather than the more costly and logistically difficult longitudinal studies.

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.

Purpose: Three previous mitomycin-cisplatin-based chemotherapy trials conducted within the EORTC Gynecological Cancer Cooperative Group (GCCG) in patients with disseminated squamous-cell carcinoma of the uterine cervix (SCCUC) suggested that with such regimens a higher overall response rate and a higher complete response rate could be obtained compared to what might have been expected from cisplatin alone. In that respect the combination of bleomycin, vindesine (Eldesine), mitomycin C and cisplatin (BEMP) was the most promising. In the present study BEMP has been compared with the best single agent, cisplatin (P) in the expectation that improved response rates might translate into a better survival., Patients and Methods: Eligible patients were those with SCCUC and disseminated measurable disease outside previously irradiated areas, aged < or = 75 years, with a WHO performance status < or = 2 and adequate bone marrow, renal, hepatic and pulmonary function, who gave consent according to regulations followed in individual institutions. Patients were randomized to BEMP: E 3 mg/m2 day 1, P 50 mg/m2 day 1, B 15 mg (24-hour infusion) day 2-4 and M 8 mg/m2 (at alternate cycles), or P 50 mg/m2. The first four cycles were given every 3 weeks (induction phase). Subsequent cycles were given every four weeks (maintenance phase), during which B was deleted from BEMP (MEP). Patients failing on P could be treated with BEM. Of the 287 patients entered, 235 were eligible and 201 evaluable for response., Results: BEMP induced a significantly higher response rate than P (42% vs. 25%, P = 0.006). There was no difference in complete response rate (11% vs. 7%). BEMP was significantly more toxic than P (+/- BEM), both with respect to hematologic and nonhematologic toxicities. After a median follow-up of 6.1 years, survival curves were not significantly different. Median progression-free survival and overall survival were 5.3 and 10.1 months with BEMP and 4.5 and 9.3 months with P (+/- BEM), respectively. In a multivariate analysis of prognostic factors for survival, a lower age (P = 0.003), a lower performance status (P = 0.0001) and a short (<1 year) interval since diagnosis (P = 0.0152) were all associated with an increased risk of dying. For progression-free survival, lower age, prior radiotherapy, locoregional involvement and no prior surgery were associated with a high risk. Treatment with BEMP or P had no significant impact on survival, but for progression-free survival there was a trend in favor of BEMP (P = 0.0893). Adjusting for prognostic factors did not change the effect of treatment., Conclusions: Combination chemotherapy with BEMP produces more toxicity and more responses compared with cisplatin alone in patients with disseminated SCCUC, but this does not translate into a better survival. Therefore, in the palliative setting single-agent cisplatin should remain the standard therapy for these patients.

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.

Background: Recent reports of variant (non-subtype B) HIV infections in US populations have raised concerns about the sensitivity of subtype B virus-based donor screening and diagnostic assays. This study was designed to determine the prevalence and genetic diversity of HIV subtypes in US blood donors over the last two decades., Study Design and Methods: Three groups were studied: hemophiliacs infected by clotting factor concentrates in the early 1980s (n = 49), blood donors retrospectively identified as being seropositive in 1985 (n = 97), and blood donors identified as seropositive between 1993 and 1996 (n = 405). Subtype assignment was based primarily on heteroduplex mobility analysis (HMA) of HIV-1 env, with DNA sequence confirmation of selected specimens. HIV peptide-based EIA serotyping was used to rule out HIV-2 and group O infections and to serotype HMA-refractory specimens., Results: Of 551 specimens, 535 (97%) were assigned subtypes; 532 (99%) of these were subtype B. Three postscreening donations (1%) were assigned non-B subtypes (2 A, 1 C). Two of these three donors were born in Africa; the third was born in the United States and reported no risk factors other than heterosexual activity. HMA distribution plots showed an increase in env diversity among HIV-1 group B strains over time., Conclusion: The results support the need for continued surveillance of HIV subtype diversity and ongoing validation of the sensitivity of HIV diagnostic assays to non-B subtype infections.

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.)

A protective herd effect has been described after susceptible populations of children are vaccinated with conjugate Haemophilus influenzae type b (Hib). Hib carriage was studied in children aged 6-24 months attending day care centers in two cities in southern Brazil (Curitiba and Porto Alegre). In Curitiba, routine immunization with Hib polyribosylribitol phosphate polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) in combination with diphtheria-tetanus toxoids-pertussis vaccine (PRP-T/DTP) has been offered since September 1996; DTP vaccine alone is routinely given in Porto Alegre. Children in Porto Alegre (n=643) were 8 times less likely to have received adequate Hib vaccination and 4 times more likely to be Hib carriers than children in Curitiba (n=647; i.e., point prevalence of oropharyngeal colonization, 4.8% vs. 1.2%). Point prevalence of carriage with non-type b or other nontypeable Hi was similar in children of both cities. There was a vaccination effect on carriage rates in children who received a primary 3-dose series, independent of the booster dose, suggesting that a booster may be unnecessary to induce population protection.

Cardiac tissue is densely innervated by sensory neurons that are believed to play important modulatory roles in cardiac functions. In this study, pretreatment of neonate rats with capsaicin was performed. In adult rats, cardiomyocyte size and amount of fibrous tissue in left ventricles as well as in vitro coronary flow were evaluated. The chronotropic and inotropic responses to beta-adrenoceptor agonists (norepinephrine and isoproterenol), muscarinic agonists (carbachol and pilocarpine), and calcitonin gene-related peptide (CGRP) were also investigated with the use of the isolated right atria preparation. Capsaicin pretreatment significantly (P<0.05) reduced both basal coronary flow (18% reduction) and cardiomyocyte size (34% reduction) without affecting the amount of fibrous tissues in the left ventricles. The positive inotropic and chronotropic effects in response to norepinephrine in the isolated rat heart did not significantly differ between control and capsaicin-treated rats. Similarly, the positive chronotropic effects in response to norepinephrine, isoproterenol, and CGRP as well as the negative chronotropic responses to carbachol and pilocarpine in the isolated right atria were not affected by capsaicin pretreatment. Our data are consistent with the suggestion that reductions of both basal coronary flow and cardiomyocyte size seen in hearts from capsaicin-pretreated rats may be consequences of CGRP depletion. The cardiomyocyte size reduction produced by capsaicin treatment may be related to a modulatory role of CGRP as a growth factor.

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.

BCG-test reaction was carried out in 91 non-tuberculous children between 2 and 11 years old, who had received BCG vaccination during the first six months of life to critically evaluate the usefulness of this test in Pediatric practice. The BCG-test profile of the vaccinated group was shown to have a unimodal distribution, varying from 3 to 17 millimeters, with a median of 6 millimeters. It was demonstrated that the degree of reaction decreases with time. Nevertheless, false-positives could be expected in a significant percentage when reactions larger than 10 millimeters are considered as a cutoff. The specificity can be increased using only reactions with diameter equal or greater than 15 millimeters as an indicator of tuberculous disease.

At the end of 1991 an enquiry was sent to 40 doctors recognized as experts in Gynaecological Oncology in the E.C. countries to establish the situation of this sub or superspecialty and 32 (80%) answers were received. Inside the E.C. countries only the United Kingdom recognized the subspecialty of Gynaecological Oncology. Concerning the other 11 countries, except Denmark, their experts (invited to answer the questionnaire) consider it is necessary to individualize Gynaecological Oncology as a sub or a superspecialty. Before a training period of 24 or 36 months in Gynaecological Oncology, it is necessary to have the specialty of Obstetrics/Gynaecology. The training period must include 50% or 60% in diagnosis and surgical treatment, 10% in radiotherapy (only theoretical), 10% or 20% in medical oncology (theoretical and practical), 5% or 10% in oncological pathology, basic sciences and general aspects of cancer. Breast diseases, including breast cancer, must be a part of the training in Gynaecological Oncology and at the end of this period an evaluation test must be made. Lastly, the health authorities, of each country, are the best able to recognize the individualization of Gynaecological Oncology.

The development of resistance to antibiotics can present a major problem when treating serious bacterial infections. Resistance may be increased due to indiscriminate prescribing and variations in resistance to an antibiotic may reflect different prescribing habits. In Latin American countries, where use of antibiotics is poorly controlled, resistance to gentamicin, tobramycin and amikacin, for example, is considerably higher than that found in Europe and the USA, where tighter restrictions are imposed. It is concluded that vigilance in the prescribing of antibiotics should be observed to prevent further increases in resistance.

The possible advantage of adding cisplatin (P) to cyclophosphamide (C) + adriamycin (A) in the management of stages III and IV ovarian cancer of epithelial origin was tested in a trial in which 149 patients were randomized to receive, after initial surgery, either CAP (C = 600 mg/sqm, A = 45 mg/sqm, P = 50 mg/sqm) or CA (C = 600 mg/sqm, A = 45 mg/sqm) every 4 weeks for 6 to 12 cycles, at which time follow-up laparotomoy was to be performed in responding or clinically disease-free patients. Fifteen patients were not included in the final analysis and the remaining 134 patients were considered fully or partially evaluable and are used in analysis of response and survival. The complete and partial response rates were 45.6% in the CAP arm and 45.4% in the CA arm, but the CAP regimen is of special importance in patients with bulky disease. Median survival CAP = 24 m and CA = 24.2 m), time to progression and survival was found not significantly different when CAP and CA were compared. However, more patients in the CA regimen had no macroscopic disease left after surgery than in CAP regimen (11 versus 6) and more patients in the CAP arm dose reductions and schedule delays than in the CA arm (61.1% versus 38.2%).

Bleomycin was administered by continuous i.v. infusion at a dose of 20 mg/m2/day for 7 days to 18 evaluable patients with advanced ovarian epithelial cancer resistant to conventional chemotherapy. The toxicity pattern was no different from that known from earlier studies using continuous infusion of bleomycin with the exception of the occurrence of a life-threatening allergic reaction in one patient, which led to discontinuation of treatment after 3 days. Only one patient showed a partial response for 2 months (5.5%), indicating that the drug has no significant activity in this unfavorable group of patients.

The authors present a study on the immunoglobulins in 156 women who are divided into three groups: 81 with cancer of the ovary 54 normal controls and 21 controls who had some disease other than a malignant tumour of the ovary. The radio-immuno-diffusion technique of Mancini was used to estimate the levels of immunoglobulins. The authors conclude: that as far as immunoglobulins IgG and IgA go there is no significant difference in the groups that were looked at. As far as Ig M is concerned there is a significant rise in the level in women with primary malignant tumours of the ovary, whether they had clinical signs or symptoms or none. As far as the ratio between IgA and IgG is concerned there is a significant rise in the control group with malignant disease and in a sub-group of primary malignant tumours of the ovary who had clinical manifestations of the disease. This work fits into the framework of a larger study concerned with non-specific cellular immunity in patients who have a primary malignant tumour of the ovary. It is the first of the results that have come through and will be followed more deeply and more systematically.

Studies to determine the total number of circulating lymphocytes and their morphologic transformation in the presence of phytohemagglutinin and pokeweed mitogen were carried out in 156 women: 81 who currently had an ovarian cancer or who had had it in the past; 54 normal women; and 21 patients with malignant diseases. The latter two groups served as controls. The total number of circulating lymphocytes is an important cosideration, as there is a significant decrease of lymphocytes in patients with ovarian cancer, a factor with great bearing on prognosis. The lymphoblastic transformation test in the presence of phytohemagglutinin and pokeweed mitogen showed not only significant changes in patients with ovarian cancer but also a correlation with survival at 6 months.