Effect of anaesthetic technique on mortality following major lower extremity amputation: a propensity score-matched observational study.

We investigated whether the type of anaesthesia affects mortality and length of stay after non-traumatic major lower extremity amputations. A total of 1365 eligible patients who were operated on between 2002 and 2010 were included in the final analysis. Propensity score matching was used to produce 475 matched pairs of patients undergoing operation with either general or regional anaesthesia. We found that 30-day mortality was significantly greater in the general anaesthesia group compared with the regional anaesthesia group, with an odds ratio (95% CI) of 1.5 (1.0-2.3) in the total matched population and 4.2 (1.3-13.4) in a high-risk subgroup. The median (IQR [range]) length of postoperative hospital stay was significantly less in the patients of the high-risk subgroup who had general anaesthesia at 15 (7-21 [1-101]) days compared with 25 days (10-37 [0-78]) for those who had regional anaesthesia (p = 0.027). The results of our study suggest that 30-day mortality is significantly higher in patients undergoing major lower extremity amputations under general anaesthesia compared with regional anaesthesia.

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Comprehensive study of lead pollution in Shanghai by multiple techniques.

Aerosol samples of PM10 particulates were examined with particle-induced X-ray emission (PIXE and micro-PIXE ), inductively coupled plasma-mass spectrometry, and X-ray absorption fine structures (XAFS) to investigate atmospheric Pb concentrations and its chemical species and to decide the source assignment. From the elemental analyses, lead concentrations were averaged at 369 and 237 ng.m-3 in aerosol samples of PM10 collected from 19 monitor sites in Shanghai in the winter of 2002 and 2003, respectively. The XAFS results show that major chemical forms of the lead particulates are probably PbCl2, PbSO4, and PbO. A calculation of isotope ratio and chemical mass balance of the PM10 samples revealed that the atmospheric lead particulates in Shanghai in the two periods were mainly from coal combustors, iron and steel plants, and automobile exhausts, with coal combustion dominating the lead pollution after the phasing out of leaded gasoline in 1997 in Shanghai.

Comparison of the re-usable LMA Classic and two single-use laryngeal masks (LMA Unique and SoftSeal) in airway management by novice personnel.

In a single-blind randomized trial, three types of laryngeal masks: the reusable LMA Classic, the single-use LMA Unique and SoftSeal were inserted by novice medical officers in anaesthesia. Five successive attempts were undertaken with each mask type. The order of the mask type insertion was randomly selected. Mean (SD) insertion times for LMA Classic, LMA Unique and Soft Seal were 32.9 (12.3), 39.6 (23.4) and 49.4 (50.4) seconds respectively. Differences were only significant between LMA Classic and SoftSeal (P=0.012). There were no significant differences in first attempt success rates (LMA Classic 80%, LMA Unique 77% and SoftSeal 62%). The SoftSeal was most frequently associated with blood on the mask (32%) compared to the LMA Unique (9%) and LMA Classic (6%). Sore throat was experienced in 14% of patients in the LMA Unique group versus 41% and 42% in the LMA Classic and SoftSeal groups respectively. Mean +/- SD oropharyngeal leak pressure was significantly higher in the SoftSeal (21+/-6 cmH2O) compared to the LMA Classic (17+/-7 cmH2O) and LMA Unique (16+/-6 cmH2O). Novice medical doctors can be taught to insert disposable laryngeal masks. The SoftSeal took longer to insert, which resulted in a higher incidence of blood on the mask, but success rates did not differ The LMA Unique was associated with the lowest incidence of sore throat in the immediate postoperative period. A higher oropharyngeal leak pressure with the SoftSeal may indicate improved airway seal and protection against aspiration.

Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues.

Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.

Progesterone induces focal adhesion in breast cancer cells MDA-MB-231 transfected with progesterone receptor complementary DNA.

Since the effects of progesterone are mediated mainly via estrogen-dependent progesterone receptor (PR), the expression of the effects of progesterone may be masked or overridden by the influence of estrogen under conditions in which priming with estrogens is required. We have established a PR-positive but estrogen receptor-alpha (ER-alpha) negative breast cancer cell model by transfecting PR cDNA into ER-alpha- and PR-negative MDA-MB-231 cells in order that the functions of progesterone can be studied independently of estrogens. We have demonstrated using this model that progesterone markedly inhibited cell growth. We have also discovered that progesterone induced remarkable changes in cell morphology and specific adhesion structures. Progesterone-treated cells became considerably more flattened and well spread than vehicle-treated control cells. This was associated with a striking increase of stress fibers, both in number and diameter, and increased focal contacts as shown by the staining of focal adhesion proteins paxillin and talin. There were also distinct increases in tyrosine phosphorylation of focal adhesion protein paxillin and focal adhesion kinase in association with increased focal adhesion. The staining of tyrosine-phosphorylated proteins was concentrated at focal adhesions in progesterone-treated cells. More interestingly, monoclonal antibody (Ab) to beta1 integrin was able to inhibit progesterone-induced cell spreading and formation of actin cytoskeleton. To our knowledge, this is the first report describing a direct effect of progesterone in inducing spreading and adhesion of breast cancer cells, and beta1-integrin appeared to play an essential role in the effect. It is known that the initial step of tumor metastasis is the breakaway of tumor cells from primary tumor mass when they lose the ability to attach. Hence, progesterone-induced cell spreading and adhesion may have significant implications in tumor metastasis.

Progestins inhibit the growth of MDA-MB-231 cells transfected with progesterone receptor complementary DNA.

Because progesterone exerts its effects mainly via estrogen-dependent progesterone receptor (PgR), the expression of progesterone's effects may be overshadowed by the priming effect of estrogen. PgR expression vectors were transfected into estrogen receptor (ER)-alpha and PgR-negative breast cancer cells MDA-MB-231; thus the functions of progesterone could be studied independent of estrogens and ERs. Eight stable transfectant clones expressing both PgR isoform A and B were studied for their growth response to progesterone and its analogues. Although progesterone had no effect on growth in the control transfectant, the hormone markedly inhibited DNA synthesis and cell growth in all of the PgR-transfectants dose-dependently from 10(-12)-10(-6) M. This growth inhibition was associated with an arrest of cells in the G0/G1 phase of the cell cycle. Progestins medroxyprogesterone acetate, Org2058, and R5020 also strongly inhibited DNA synthesis, and their doses required for maximal inhibition of 60-70% were 10(-17) M, 10(-13) M, and 10(-7) M, respectively. Antiprogestin ZK98299 alone had no effect, but the compound was capable of counteracting the inhibitory effect of progesterone. In contrast, RU486 inhibited DNA synthesis, and it showed no further effects when it was used concurrently with progesterone. These results indicate that progestins are per se antiproliferative via a PgR-mediated mechanism in breast cancer cells. More importantly, we have shown that progestins may exert effective inhibitory control over the cell growth if the PgR expression is reactivated in ER- and PgR-negative breast cancer cells.

Preliminary study of the distribution of the toxic elements As, Cd, and Hg in human hair and tissues by RNAA.

In order to study the relationships between trace element concentrations of hair and internal body burdens, a radiochemical NAA technique has been used for determination of the elements As, Cd, and Hg in autopsy samples of liver, kidney-cortex, lung, and hair from 24 male persons who died by accident. High significant positive correlations were observed between the As concentration in hair and in kidney-cortex, and between Cd and Zn concentrations in kidney-cortex. The contents of Cd, both for lung and kidney-cortex, were related to the smoking habits of the subjects.

Study of correlation of Se content in human hair and internal organs by INAA.

The correlations of essential element Se between human hair and kidney-cortex, liver, and lung from the same subjects were investigated by instrumental neutron activation analysis, using the reaction 76Se (n, gamma) 77mSe, for 24 Chinese autopsies. The concentration of Se is higher in kidney-cortex (2.04-5.36 mg/kg) than in liver (0.73-2.29), lung (0.50-1.85), and hair (0.37-1.43). It is important to know that there are significant relationships of Se concentration between hair and the other three internal organs. The correlation coefficient by linear regression analysis are 0.639, 0.570, and 0.635 for liver, lung, and kidney-cortex, respectively; and the P values are all less than 0.01 for the three tissues.