Estradiol decreases blood pressure in association with redox regulation in preeclampsia

In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O₂.), hydrogen peroxide (H₂O₂), nitrites (NO₂^?), and peroxynitrite (ONOO^?) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O₂^– and H₂O₂, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO₂^– as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O^.–, H₂O₂, NO₂^?, and ONOO^– in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O₂^–, H₂O₂, and ONOO^– was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.     

The impact of tumor size on outcomes in patients with upper urinary tract urothelial carcinoma

Purpose

To investigate the association between tumor size and clinicopathologic factors and outcomes of upper urinary tract urothelial carcinoma (UTUC) in patients treated surgically for UTUC.

Methods

A single-center series of 235 consecutive patients who were treated surgically for UTUC between January 1999 and December 2011 was evaluated. Patients with a history of muscle-invasive urothelial carcinoma of the urinary bladder, those who received neoadjuvant therapies, and those with previous contralateral UTUC were excluded. Bladder-only recurrence, any recurrence, and cancer-specific mortality after surgery were analyzed. Recurrence-free probabilities and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method and Cox regression analyses.

Results

Tumor size was significantly associated with age of the patient (P = 0.001), tumor location (P < 0.0001), tumor multifocality (P = 0.005), higher tumor stage (P < 0.0001), higher tumor grade (P = 0.038), lymphovascular invasion (P = 0.002), and mode of operation (P = 0.001). Tumor size was not associated with bladder-only recurrence (HR 0.91; 95 % CI 0.46–1.80; P = 0.79). The Kaplan–Meier method showed that tumor size >3 cm was significantly associated with worse CSS (P = 0.006, log rank). The 5-year CSS for patients with tumor size ≤3 cm was 70.1 % and for patients with tumor size >3 cm was 56.1 %. Tumor size was not associated with cancer-specific survival in multivariable analysis (HR 1.53; 95 % CI 0.89–2.61; P = 0.12).

Conclusions

Tumor size >3 cm was associated with a lower 5-year CSS at Kaplan–Meier analysis, but was not an independent predictor of CSS, bladder-only recurrence, and any recurrence-free survival at multivariable analysis.     

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma

ObjectiveTo evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer.Patients and methodsA single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36–88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses.ResultsFifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers.ConclusionsPatients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC.     

Artritis temporomandibular por Mycobacterium bovis. Un problema diagnóstico

Infrequent variants of extrapulmonary tuberculosis pose a challenging public health problem because of the delay in their diagnosis and treatment. Joint involvement is usually encountered in major joints (hip, elbow, knee and ankle). Tuberculous involvement of the temporomandibular joint is extremely uncommon but must be considered in patients with pain, inflammation or joint stiffness not resolved with conventional treatment.     

An HIV type 1 subtype A outbreak among injecting drug users in Kazakhstan

Kazakhstan experienced the start of the HIV-1 outbreak among intravenous drug users (IDUs) in 1997. To characterize genetically HIV-1 strains circulating in this country, peripheral blood mononuclear cells (PBMCs) DNA samples (1999-2002) derived from HIV-infected IDUs and their sexual partners in Pavlodar (n = 19), Shymkent (n = 6), and Qaraghandy (n = 18) regions were analyzed by the gag/env heteroduplex mobility assay (HMA). The 366-bp proviral env gene fragments encoding the gp120 C2-V3 region obtained from 16 individuals were sequenced. The results of HMA revealed that all 43 HIV-1 strains studied belonged to gag/env subtype A. The nucleotide sequence analysis showed a marked genetic homogeneity with the mean genetic distance being 3.63 +/- 2.39 (range 0.00-12.13). The mean genetic distance between each sequence within the Kazakhstan set and the East-European IDU subtype A consensus was 2.94 +/- 1.92 (range 0.79-8.48). The data presented thus confirm the spreading of the same IDU subtype A virus in the former Soviet Union.     

The effect of paracetamol on peritoneal reflex after single and multiple grapefruit ingestion.

In the last few years, more attention has been paid to the influence of grapefruit juice on metabolism on many drugs. It has been reported that grapefruit juice increases the plasma concentrations of orally administrated drugs, that undergo metabolism in liver. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice could also cause these effects. Paracetamol is metabolized by reactions of oxidation and conjugation to nontoxic ineffective metabolites. These reactions, partly catalyzed by cytochrome P450 izoenzymes, take place in liver. The analgesic effect of paracetamol was examined by Writhing tests, where we used acetic acid as an irritating agent. We used three groups of male mice: the control group, the group which was administrated 0.2 mL of grapefruit juice per os 10 days (GPOch) and the group which was administrated single dose of 0.5 mL grapefruit juice per os 90 min. before the experiment (GPOac). Dose of 50 mg/kg of paracetamol was applicated s.c. 5 min. before i.p. application of 3 % acetic acid. The writhing phenomenon was observed in periods of 5-15 min. and 15-30 min. after the application of paracetamol. The results show that paracetamol in GPOch group significantly decreases irritant effect of acetic acid in the period of 15-30 min. after the application in relation to the control group. However, the acetic acid shows stronger irritant effect in GPOch group than in the control group and less irritant effect in GPOac group than in the control group. In the period of 5-15 min. after the application, paracetamol shows analgesic effect neither in the control nor in the other groups.     

Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance

Serum aminoglutethimide was measured in 13 women with mastastatic breast carcinoma who were treated with 1.0 Gm aminoglutethimide and 40 mg hydrocortisone daily over a period of one year. Serum concentrations of aminoglutethimide were used to evaluate drug half-life, clearance, and patient compliance. Mean half-life and clearance rates were determined in six patients. The mean half-life of aminoglutethimide prior to therapy was 13.3 +/- 2.65 (S.D.) hours and fell significantly (P less than 0.01) to 7.3 +/- 2.14 hours after six to 32 weeks of therapy. The mean clearance rate prior to therapy was 2.58 +/- 0.33 (S.D.) 1./hour and increased significantly (P less than 0.01) to 5.29 +/- 1.4 1./hour after therapy. The mean serum concentration was 11.5 +/- 3.6 microgram/ml in seven patients. No significant variation of mean aminoglutethimide concentration from the overall mean was noted during the course of therapy. We conclude that serum aminoglutethimide concentrations are useful in evaluating patient compliance. Our data also suggest that aminoglutethimide increases its own metabolism, which may explain the absence of toxicity symptoms seen late in the treatment period.     

Adrenal suppression with aminoglutethimide. III. Comparison of plasma delta 4- and delta 5-steroids in postmenopausal women treated for breast carcinoma.

A regimen or aminoglutethimide in combination with replacement glucocorticoid has been used to suppress adrenal steroidogenesis in postmenopausal women with metastatic breast carcinoma. During acute and chronic treatment with aminoglutethimide, the levels of the delta 4-steroids [progesterone (P), 17 alpha-hydroxyprogesterone (17-delta 4-P), and androstenedione (delta 4-A)] and the delta 5-steroids [dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and 17 alpha-hydroxypregnenolone (17-delta 5-P)] were determine. In the total group of women, the plasma levels of P and delta 4-A increased 2- to 3-fold (P less than 0.05) while 17-delta 4-P rose 10-fold (P less than 0.01) from basal concentrations of 0.65 +/- 0.07 to 6.48 +/- 1.46 ng/ml during the initial 2 weeks of therapy with aminoglutethimide (AG) and dexamethasone. These three steroids then fell to basal levels during chronic treatment (P and 17-delta 4-P) or were suppressed (delta 4-A; P less than 0.001). In contrast, the levels of delta 5-steroids (17-delta 5-P, DHEA, and DHEA-S) were reduced 3- to 5-fold during the initial 2 weeks of therapy and remained suppressed throughout. The relative levels of certain delta 5- and delta 4-steroids pairs were then examined. The ratio of 17-delta 5-P to 17-delta 4-P decreased from baseline values of 2.15 +/- 0.35 to 0.38 +/- 0.21 ng/ml (P less .02) with the initiation of therapy and remained low thereafter. A similar pattern for the ratios between DHEA and delta 4-A, and DHEA-S and delta 4-A was observed. This may indicate that the regimen of AG treatment utilized may facilitate the activity of the 3 beta-ol-dehydrogenase, delta 5- to delta 4-isomerase, and accelerate the conversion of delta 5- to delta 4-steroids. The patterns of suppression of the plasma delta 4- and delta 5-steroids in oophorectomized and spontaneously postmenopausal patients with intact ovaries were analyzed separately. The plasma levels of progesterone were higher during the first 2 weeks of therapy in surgically castrate women than in spontaneously postmenopausal women (0.72 +/- 0.25 vs. 0.47 +/- 0.20 ng/ml). A similar pattern was observed for 17-delta 4-P, DHEA, and DHEA-S indicating that the adrenals might contribute to this increase. In contrast, during chronic treatment the levels of all steroids were lower in surgically castrate women than in those with intact ovaries. This suggested residual ovarian steroid during AG administration.