Toluidine blue for the intraoperative staining of the ureters. Studies on the safe administration in rats.

PURPOSE: Acute cardiovascular events have repeatedly been reported to occur during the intraoperative presentation of the urinary tract with toluidine blue (TB). We here assessed the minimum TB dose required, and its safest and most suitable form of intravenous administration for the intraoperative staining of the ureters in rats. METHODS: TB (0.13, 0.4, 1.3, or 4.0 mg/kg) was administered to anesthetized rats either by intravenous injection within 1 min or by infusion within 10 min. During the experiments,biomonitoring parameters such as electrocardiograms (ECGs)and mean arterial blood pressure (MAP) were recorded,blood gas analysis was performed, and methemoglobin measured. Tissue injury was assessed from released plasma enzyme activities and histopathologically. The intraoperative staining of the ureters was documented photographically,and total urinary excretion and final urine/plasma TB concentrations were determined. RESULTS: Parameters of blood gas analysis, methemoglobin concentrations, and markers of tissue injury were slightly affected by the two highest TB doses but not at all by the lower ones. At doses of ≥0.4 mg/kg, ureters were stained sufficiently. Staining was more intense, and urine excretion of TB higher on average when the dye was injected.The 1-min injection of ≥1.3 mg TB/kg strongly and temporarily decreased the MAP, while the infusions caused lesser effects. Mean ECG parameters were not affected by any TB administration, but one animal developed a temporary bundle branch block after the 1-min injection of 4.0 mg/kg. CONCLUSIONS: In rats, intravenous injection of 0.4 mg TB/kg was sufficient for the intraoperative staining of the urinary tract without the risk of severe cardiovascular and hemodynamic side effects. Provided our results are transferable to humans, the administration of low TB doses could allow its safer clinical use for the intraoperative visualization of the ureters.

High-frequency oscillatory ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: High-frequency oscillatory ventilation (HFOV) is usually considered not indicated for treatment of patients with chronic obstructive pulmonary disease (COPD) because of the theoretical risk of air trapping and hyperinflation. The aim of our study was to establish whether HFOV can be safely applied in patients with acute exacerbation of COPD and hypercapnic respiratory failure. METHODS: Ten patients (age, 63-83 years) requiring intensive care treatment who failed on noninvasive ventilation were studied. After initial conventional mechanical ventilation (CMV) of less than 72 hours, all patients were transferred to HFOV for 24 hours and then back to CMV. Arterial blood gases, spirometry, and hemodynamic parameters were repeatedly obtained in all phases of CMV and HFOV at different settings. Regional lung aeration and ventilation were assessed by electrical impedance tomography. RESULTS: High-frequency oscillatory ventilation was tolerated well; no adverse effects or severe hyperinflation and hemodynamic compromise were observed. Effective CO(2) elimination and oxygenation were achieved. Ventilation was more homogeneously distributed during HFOV than during initial CMV. Higher respiratory system compliance and tidal volume were found during CMV after 24 hours of HFOV. CONCLUSIONS: Our study indicates that short-term HFOV, using lower mean airway pressures than recommended for acute respiratory distress syndrome, appears safe in patients with COPD while securing adequate pulmonary gas exchange.

6p21 rearrangements in uterine leiomyomas targeting HMGA1.

To quantify the expression of HMGA1 mRNA in uterine leiomyomas, the expression of HMGA1 was analyzed in a series including tumors with aberrations of chromosome 6 (n = 7) and cytogenetically normal tumors (n = 8) as a control group by quantitative reverse transcriptase-polymerase chain reaction. The average expression level in the 6p21 group was found to be 5.6 times higher than that in the control group, and with one exception, all cases with 6p21 alteration revealed a high expression of HMGA1 mRNA than cytogenetically normal tumors. Nevertheless, compared to fibroids with a normal karyotype, the upregulation of the HMGA1 mRNA in these cases was much less strong than that of HMGA2 mRNA in case of 12q14∼15 aberrations identified in previous studies.

Lipase LipC affects motility, biofilm formation and rhamnolipid production in Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces and secretes several lipolytic enzymes, among them the lipases LipA and LipC. LipA is encoded within the lipA/lipH operon, together with its cognate foldase LipH, which was also found to be required for the functional expression of LipC. At present, the physiological function of LipC is unknown. We have cloned a synthetic operon consisting of the lipC structural gene and the foldase gene lipH obtained from the lipA/lipH operon and have constructed, in parallel, a lipC-deficient P. aeruginosa mutant. Inactivation of the lipC gene significantly impaired type IV pilus-dependent twitching and swarming motility, but also the flagella-mediated swimming motility of P. aeruginosa. Moreover, for the lipC mutant, we observed a significant decrease in the amount of extracellular rhamnolipids. Also, the P. aeruginosa lipC mutant showed a significantly altered biofilm architecture. Proteome analysis revealed the accumulation of the response regulator protein PhoP in the lipC mutant.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status.

OBJECTIVE: To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: University hospitals. PATIENT(S): A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). INTERVENTION(S): Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. MAIN OUTCOME MEASURE(S): Measurement of myoma volume and E(2), FSH, LH, and T levels. RESULT(S): Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. CONCLUSION(S): Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma.

Modeling nonlinear phase noise in differentially phase-modulated optical communication systems.

Using an alternative approach for evaluating the Bit-Error Rate (BER), we present a numerical and experimental investigation of the performance of phase-modulated optical communication systems in the presence of nonlinear phase noise and dispersion. The numerical method is based on the well known Karhunen-Lo;eve expansion combined with a linearization technique of the Nonlinear Schr odinger Equation (NLSE) to account for the nonlinear interaction between signal and noise. Our numerical results show a good agreement with experiments.

Overexpression of HMGA2 in uterine leiomyomas points to its general role for the pathogenesis of the disease.

An overexpression of HMGA2 is supposed to be a key event in the genesis of leiomyoma with chromosomal rearrangements affecting the region 12q14-15 targeting the HMGA2 gene, but gene expression data regarding differences between uterine leiomyomas with and those without 12q14-15 aberrations are insufficient. To address the question whether HMGA2 is only upregulated in the 12q14-15 subgroup, the expression of HMGA2 was analyzed in a comprehensive set of leiomyomas (n = 180) including tumors with 12q14-15 chromosomal aberrations (n = 13) and matching myometrial tissues (n = 51) by quantitative RT-PCR. The highest expression levels for HMGA2 were observed in tumors with rearrangements affecting the region 12q14-15, but although HMGA2 is expressed at lower levels in leiomyomas without such aberrations, the comparison between the expression in myomas and matching myometrial tissues indicates a general upregulation of HMGA2 regardless of the presence or absence of such chromosomal abnormalities. The significant (P < 0.05) overexpression of HMGA2 also in the group of fibroids without chromosomal aberrations of the 12q14-15 region suggests a general role of HMGA2 in the development of the disease.

Radiological findings, pulmonary function and dyspnea in underground coal miners.

BACKGROUND: Respiratory disability induced by dust exposure in coal workers is assessed by pulmonary function tests and radiological evidence of pneumoconiosis. High-resolution computed tomography (HR-CT) improves the visibility of tissue changes, but the value of the findings for the clinical evaluation is controversial. OBJECTIVES: It was the aim of this study to evaluate the correlation between the International Labour Office (ILO) classification and the degree of emphysema in HR-CT with self-reported dyspnea and pulmonary function tests including diffusion capacity for CO (DL,CO). METHODS: We investigated 87 coal miners (aged 67+/-6 years), having worked underground for 26+/-9 years, with pulmonary function tests and HR-CT. Univariate associations were tested with correlation coefficients, and multivariable analyses used a stepwise forward regression model. RESULTS: No aspect of the ILO classification showed a univariate correlation with dyspnea or forced expiratory flow in 1 s (FEV1). Emphysema CT score was strongly associated with DL,CO (rs=-0.40; p<0.001) and FEV1/maximal vital capacity (r=-0.38; p<0.001) in univariate analysis, but not with the clinical grade of dyspnea (r=-0.14; p=0.256). CT emphysema score but not ILO classification was associated with FEV1 in multivariable analyses (rs=-0.37; p<0.001). Dyspnea was best approximated by DL,CO (r=-0.312; p=0.008). CONCLUSION: The clinical grade of breathlessness was best approximated by DL,CO. HR-CT showed a good association with expiratory flow limitation. ILO classification of the chest radiograph may be a marker of exposure but conveys little information about the degree of respiratory impairment.

Hysteroscopic metroplasty of the complete uterine septum, duplicate cervix, and vaginal septum.

OBJECTIVE: To determine if sectioning of the cervical septum in hysteroscopic metroplasty of the complete uterine septum is associated with intraoperative bleeding, cervical incompetence, and secondary infertility. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: University hospitals. PATIENT(S): Twenty-eight women with a diagnosis of complete uterine septum who had a history of pregnancy wastage or infertility. They were randomized into two groups: group A underwent metroplasty including section of the cervical septum; group B underwent the same procedure with preservation of the cervical septum. INTERVENTION(S): Hysteroscopic metroplasty was performed for all patients in the two groups. MAIN OUTCOME MEASURE(S): Operating time, distending media deficit, total distending media used, intraoperative bleeding, complications, and reproductive outcome. RESULT(S): Operating times were 36.40 +/- 10.67 minutes and 73 +/- 14.40 minutes in group A and group B, respectively. Distending media deficit was 456.66 +/- 165.68 mL in group A, while in group B it was 673.84 +/- 220.36. Two cases of pulmonary edema and three cases of significant bleeding (> 150 mL) were seen in group B. The cesarean section rate was significantly higher in group B. There were no significant differences in the reproductive outcome in the two groups. CONCLUSION(S): Resection of the cervical septum during hysteroscopic metroplasty of complete uterine septum makes the procedure safer, easier, and less complicated than the procedure with preservation of the cervical septum. This procedure is recommended for all cases of complete uterine septum.

Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel.

PURPOSE: A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB-IV non-small-cell lung cancer (NSCLC) were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks (3-weekly) and 35 mg/m2 on days 1, 8, and 15 (weekly) for < or = eight cycles. End points included survival (primary), toxicity, and response. RESULTS: Of 215 patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were assessable for response. At baseline, 24.5% of patients (51 out of 208) had received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been progression-free for more than 3 months after first-line therapy. After 12 months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months) with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly docetaxel (P = .07) after a median of four (range, one to eight) and two (range, one to eight) treatment cycles, respectively. Overall, response rates were 12.6% v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel (P < or = .05). There were significantly lower rates of grade 3 to 4 anemia (P < or = .05), leucopenia (P < .0001), and neutropenia (P < or = .001) with weekly versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was reported. CONCLUSION: Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and better tolerability than standard 3-weekly docetaxel 75 mg/m2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC.

Hyperprolactinemia after laparoscopic ovarian drilling: an unknown phenomenon.

BACKGROUND: The effects of ovarian drilling on the serum levels of gonadotropins and androgens have been studied previously. The aim of this study is to evaluate the effects of ovarian drilling on the serum prolactin levels and its relation to ovulation in women with polycystic ovary syndrome. METHODS: This is a prospective controlled study. Thirty-six women with PCOS underwent ovarian electrocauterization in university hospitals. Control group consisted of 35 ovulatory women with unexplained infertility. Hormonal assessment performed in early follicular phase of spontaneous or induced cycle before operation in the two groups and repeated one week after operation. Hormonal assay was also performed in the early follicular phase of the first post-operative menstruation, folliculometry and progesterone assay were also performed in the same cycle. Data were analyzed by "repeated measurement design, discriminant analysis, correlation coefficient, and Fisher exact test". RESULTS: Six to ten weeks after operation the serum mean +/- SD prolactin levels increased from 284.41 +/- 114.32 mIU/ml to 354.06 +/- 204.42 mIU/ml (P = 0.011). The same values for the control group were 277.73 +/- 114.65 to 277.4 +/- 111.4 (P = 0.981) respectively. Approximately 45% of subjects in PCOS group remained anovulatory in spite of decreased level of LH and testosterone. Prolactin level remained elevated in 73.2% of women who did not ovulate 6-10 weeks after the procedure. CONCLUSION: Hyperprolactinemia after ovarian cauterization may be considered as a possible cause of anovulation in women with polycystic ovaries and improved gonadotropin and androgen levels. The cause of hyperprolactinemia is unknown. Hormonal assay particularly PRL in anovulatory patients after ovarian cauterization is recommended.

Combined modality treatment for locally advanced non-small cell lung cancer: preoperative chemoradiation does not result in a poorer quality of life.

The German Lung Cancer Cooperative Group (GLCCG) is assessing the impact of chemoradiation in addition to chemotherapy in the neoadjuvant treatment of stage III NSCLC. After three cycles of cisplatin/etoposide patients receive either hyperfractionated radiotherapy (RT) with concurrent carboplatin/vindesine and then surgery (arm A) versus surgery and then conventional RT (arm B). Quality of life (QL) was assessed throughout therapy using the EORTC QLQ-C30 and EORTC QLQ-LC 13. Of 126 eligible patients, 54 completed treatment. For patients in both treatment arms physical functioning decreased, whereas dyspnoea, fatigue and pain increased from beginning to the end of treatment. For self-assessed QL no statistically significant effect was found in or between the two treatment arms. The combined modality approach with preoperative radio/chemotherapy proves to be feasible in treating locally advanced NSCLC patients without decreasing their subjective QL.

A double-blind, randomized, placebo-controlled study to assess the efficacy of ketoconazole for reducing the risk of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the role of ketoconazole in prevention of ovarian hyperstimulation syndrome (OHSS) in women with the polycystic ovary syndrome (PCOS) undergoing ovarian stimulation with gonadotropins. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospitals. One hundred nine women with PCOS who were referred for treatment with gonadotropins. INTERVENTION(S): Fifty patients were randomly assigned to receive two ampoules of hMG beginning on day 2 or 3 of the cycle and ketoconazole (50 mg every 48 hours) starting on the first day of hMG treatment. Fifty-one patients received the same amount of hMG plus one tablet of placebo every 48 hours. MAIN OUTCOME MEASURE(S): Follicular development, E(2) level, and pregnancy rate. RESULT(S): The total number of hMG ampoules and duration of treatment to attain ovarian stimulation were higher among ketoconazole recipients. The serum E(2) level and number of patients with dominant follicles on day 9 of the cycle were greater in placebo recipients. Serum E(2) level and total number of follicles at the time of hCG administration did not differ between the two groups. The cancellation rate and OHSS rate were similar in the two groups. CONCLUSION(S): Ketoconazole does not prevent OHSS in patients with PCOS who are undergoing ovarian stimulation. It may reduce the rate of folliculogenesis and steroidogenesis.

Comparative, double-blind, randomized, placebo-controlled trial of intraperitoneal of bupivacaine and lidocaine for pain control after diagnostic laparoscopy.

STUDY OBJECTIVE: To compare the effect of intraperitoneal bupivacaine and lidocaine on reducing pain after diagnostic laparoscopy. DESIGN: Randomized, double-blind, placebo-controlled study (Canadian Task Force classification I). SETTING: University teaching hospital. PATIENTS: One hundred thirty-four women with unexplained infertility. INTERVENTION: Diagnostic laparoscopy with intraperitoneal administration of bupivacaine or lidocaine. MEASUREMENTS AND MAIN RESULTS: Patients were randomized into one of four groups. In group A, at the end of laparoscopy 0.125% bupivacaine 30 ml was instilled into the pelvic cavity and the same dose was instilled over the diaphragmatic vault. Groups B and C received the same volume of 5% lidocaine and normal saline, respectively. Group D received no intraperitoneal agent. The verbal pain scale questionnaire was used to assess postoperative pain. Pain scores 2 and 24 hours postoperatively were significantly lower for group A than for groups B and C (p = 0.0001). Scores in group B were also significantly lower than those in groups C and D (p = 0.0001). Women in group A required less additional analgesia than those in the other groups. CONCLUSION: Compared with lidocaine and placebo, intraperitoneal bupivacaine significantly decreased postoperative pain, and this effect was long lasting.

Ovarian stromal blood flow changes after laparoscopic ovarian cauterization in women with polycystic ovary syndrome.

BACKGROUND: Women with PCOS have significant differences in intra-ovarian and uterine artery haemodynamics. The aims of this study were to compare the ovarian stromal blood flow before and after laparoscopic ovarian diathermy, and to evaluate the value of these parameters in predicting the outcome of treatment in women with polycystic ovaries. METHODS: Colour Doppler blood flow within the ovarian stroma was recorded and serum concentrations of FSH, LH and testosterone were measured in 52 women with polycystic ovaries before and after laparoscopic ovarian diathermy. Ovulation was evaluated by folliculometry and progesterone assay in the first menstrual cycle after operation. RESULTS: Six to 10 weeks after the diathermy, serum concentrations of LH and testosterone decreased significantly (P = 0.001). The mean +/- SD peak systolic velocity decreased from 14.04 +/- 6.28 to 12.49 +/- 6.32 cm/s (P = 0.001), pulsatility index increased from 0.98 +/- 0.36 to 1.78 +/- 0.72 (P = 0.001), and resistance index increased from 0.55 +/- 0.16 to 0.71 +/- 19 (P = 0.001). A total of 73% of the women ovulated. There were significant negative correlations between pulsatility index and LH (r = -0.43, P = 0.001), pulsatility index and testosterone (r = -0.40, P = 0.003) and pulsatility index and LH/FSH ratio (r = -0.53, P = 0.001). CONCLUSIONS: Laparoscopic ovarian diathermy in women with polycystic ovary syndrome may result in a decrease in ovarian stromal blood flow velocity. There was a significant correlation between hormonal and ovarian stromal blood-flow changes. Changes in the Doppler parameters were significantly higher in women who ovulated. The measurement of ovarian stromal blood flow by colour Doppler may be of value in predicting the outcome of treatment.