Small-dose nitric oxide improves oxygenation during one-lung ventilation: an experimental study

Inhaled nitric oxide (NO) at 20 or 40 ppm does not improve arterial oxygenation during one-lung ventilation (OLV). The authors hypothesized that NO at smaller concentrations might improve oxygenation. Twelve piglets weighing 26 to 32 kg were studied. When PaO(2) had reached a plateau during OLV, NO at doses of 4, 8, 16, and 32 ppm were randomly administered for 30 min. Hemodynamic data were determined by invasive monitoring. Blood gas analysis and, in six animals, ventilation-perfusion analysis by the multiple inert gas elimination technique were used to characterize pulmonary gas exchange. NO at 4, 8, 16, and 32 ppm improved PaO(2) during OLV. NO at 4 ppm had a more intense effect on arterial oxygenation than doses of 8, 16, and 32 ppm (DeltaPaO(2), 42 +/- 35 mm Hg versus 22 +/- 20 mm Hg, 13 +/- 18 mm Hg, and 15 +/- 16 mm Hg; P < 0.05). NO at 4 ppm reduced intrapulmonary shunt flow, whereas a larger concentration exhibited no statistically significant effect. The authors conclude that NO improves arterial oxygenation more effectively at smaller doses than at larger doses. This dose-dependent effect remains to be confirmed in acute hypoxemia during OLV. IMPLICATIONS: Inhaled nitric oxide at 4 ppm improves arterial oxygenation during one-lung ventilation to a greater extent than larger doses, and this effect is caused by a reduction in intrapulmonary shunt.     

Narcotrend,bispectral index,and classical electroencephalogram variables during emergence from propofol/remifentanil anesthesia

The aim of this study was to investigate modern and classical electroencephalographic (EEG) variables in response to remifentanil and propofol infusions. We hypothesized that modern EEG variables may indicate the effects of propofol but not of remifentanil. Twenty-five patients were included in the study after the end of elective spine surgery without any surgical stimulation. Baseline values were defined with remifentanil 0.3 microg. kg(-1). min(-1) and target-controlled infusion of propofol 3.0 microg/mL. EEG changes were evaluated 1, 3, 5, 7, and 9 min after the stop of remifentanil infusion, followed by a step-by-step reduction (0.2 microg/mL) every 3 min of target-controlled infusion propofol. Narcotrend (NT; classifying EEG stages from awake to deep anesthesia), bispectral index (BIS), EEG spectral frequency bands (%), 50% (Median) and 95% percentiles (spectral edge frequency), mean arterial blood pressure, heart rate, and oxygen saturation were detected at every time point. The end of remifentanil application resulted in significant increases in %alpha, spectral edge frequency, mean arterial blood pressure, and %theta and decreases in %delta (P < 0.05). NT, BIS, Median, heart rate, and oxygen saturation were unchanged. Decreases in propofol concentration were associated with statistically significant increases in NT and BIS (P < 0.05). Thus, the sedative-hypnotic component of propofol could be estimated by modern EEG variables (NT and BIS), whereas the analgesic component provided by remifentanil was not indicated. However, during conditions without surgical stimulation, neither NT nor BIS provided an adequate assessment of the depth of anesthesia when a remifentanil infusion was used. IMPLICATIONS: We investigated modern and classical electroencephalographic (EEG) variables during emergence from propofol/remifentanil anesthesia. Modern EEG variables indicate changes of infusion in propofol, but not in remifentanil. Thus, modern EEG variables did not provide an adequate assessment of depth of anesthesia when remifentanil was used.     

Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994

BACKGROUND: Recent reports of rickets among African American children drew attention to the vitamin D status of these infants and their mothers. African American women are at higher risk of vitamin D deficiency than are white women, but few studies have examined determinants of hypovitaminosis D in this population. OBJECTIVE: We examined the prevalence and determinants of hypovitaminosis D among African American and white women of reproductive age. DESIGN: We examined 1546 African American women and 1426 white women aged 15-49 y who were not pregnant and who participated in the third National Health and Nutrition Examination Survey (1988-1994). Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D concentration < or =37.5 nmol/L. Multiple logistic regression was used to examine the independent association of dietary, demographic, and behavioral determinants of hypovitaminosis D. RESULTS: The prevalence of hypovitaminosis D was 42.4 +/- 3.1% ( +/- SE) among African Americans and 4.2 +/- 0.7% among whites. Among African Americans, hypovitaminosis D was independently associated with consumption of milk or breakfast cereal <3 times/wk, no use of vitamin D supplements, season, urban residence, low body mass index, and no use of oral contraceptives. Even among 243 African Americans who consumed the adequate intake of vitamin D from supplements (200 IU/d), 28.2 +/- 2.7% had hypovitaminosis D. CONCLUSIONS: The high prevalence of hypovitaminosis D among African American women warrants further examination of vitamin D recommendations for these women. The determinants of hypovitaminosis D among women should be considered when these women are advised on dietary intake and supplement use.     

Trichloroethanol alters action potentials in a subgroup of primary sensory neurones

We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate.     

Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cells

A central role for polo-like kinases (PLK) in regulating several stages of mitotic progression has been born out in several species. Overexpression of PLK1 is observed in the majority of hitherto analysed human tumors. PLK1 overexpression is a negative prognostic factor in patients suffering from non-small cell lung cancer, head and neck tumors, esophageal carcinomas and melanomas. In order to define the role of PLK1 for mitotic progression of human cells and for neoplastic cell growth, phosphorothioate antisense oligonucleotides (ASOs) were tested to selectively downregulate PLK1 expression in MDA-MB-435 (breast cancer), HeLa S3 (cervical carcinoma) and A549 (non-small cell lung cancer) cells. ASOs were identified which suppress PLK1 mRNA and protein in a dose-dependent and sequence-specific manner. This approach also led to reduced PLK1 serine/threonine kinase activity. Downregulation of cellular PLK1 levels in cancer cells altered cell cycle progression moderately with an elevated percentage (20-30%) of cells in G(2)/M. Furthermore, cells with reduced PLK1 protein gained a rounded phenotype with multiple centrosomes. Moreover, ASO treatment resulted in potent antiproliferative effects in cell culture. Considerable antitumor activity was observed in vivo against A549 cells. This study suggests that antisense inhibitors targeted against PLK1 at well tolerated doses may be considered as a cancer therapeutic agent.     

Chemotherapy for metastatic breast cancer-report of a European expert panel

The anthracyclines doxorubicin and epirubicin, and the taxanes paclitaxel and docetaxel, are effective chemotherapeutic agents for the first-line and second-line treatment of metastatic breast cancer, and their clinical use is widespread. However, for women whose disease has progressed despite receiving these drugs, treatment options are limited. These women often have a good performance status, and may survive for many months or even years, so they should be given the opportunity to benefit from further chemotherapy. The goals of chemotherapy in these patients are to obtain maximum control of symptoms, prevent serious complications, and increase survival without diminishing quality of life. Several agents are used for this purpose, including fluorouracil, docetaxel (in patients who have already received paclitaxel), vinorelbine, and mitomycin c, but because data from controlled trials are limited, a standard regimen has not yet been established. Moreover, these agents may be inconvenient to administer and can be associated with adverse events requiring hospitalisation. Therefore, there is a clear need for additional therapeutic options for patients with metastatic breast cancer. Ideally, agents should have a convenient method of administration, eg, oral, and should be suitable for home-based rather than hospital-based therapy. Treatment should control disease in at least 20-30% of patients with an acceptable side-effect profile. Novel oral therapies have now been developed and are being used increasingly in patients whose disease has progressed following taxane therapy.     

Postmastectomy Electron-Beam-Rotation Irradiation in Locally Advanced Breast Cancer

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.