Neutralization Procedure Research Articles

The Security Council and Territorial Sovereignty: The Case of Kosovo

AbstractMore than ten years since NATO intervened militarily to stop the violence and to create the conditions for a new regime of international administration, Kosovo remains at the top on the agenda of international actors and institutions. The present contribution examines the nature and scope of the Security Council’s action (and inaction) with regard to the political crisis and ensuing conflict emerged in Kosovo starting from the late 1990s and how that practice has shaped notions of territorial sovereignty. It analyses the different forms of international intervention in the four phases of the Kosovo controversy (from the 1998‐1999 crisis to the current situation post declaration of independence, passing through the UN administration of the territory and the negotiations on future status), the extent to which international law played a role in dictating outcomes and results and the ways in which the notion of territorial sovereignty was reinterpreted by the Council. The main conclusion reached is that, while some of the measures adopted throughout the years have introduced important novelties in the contemporary conception of territorial sovereignty, that has been the result of harsh bargaining between different states and groups of states in which the Council has only provided for the diplomatic setting, rather than the end products of the Council’s own policy and strategies. Moreover, as the current discussions over the mandate and legal basis of EULEX show, the interpretation of those measures and instruments has been remarkably at variance among the different actors, surfacing diplomatic conflicts and ‘agreements to disagree’ that have been frozen, in some cases for years, under neutral UN procedures and operational strategies.

Chitosan-Based Hydrogels for the Recovery of Precious Metals

Chitosan (an aminopolysaccharide), cross-linked with glutaraldehyde, is very efficient for Pd(II) and Pt(IV) recovery from acidic solutions (pH 2). Due to poorly porous properties, it is necessary to condition the biopolymer as hydrogels. The uncontrolled drying of hydrogels depreciates the diffusion properties of original materials. A different method (to the acidic dissolving/alkaline neutralization procedure) has been used: after chitosan dissolving in acetic acid solution, the viscous solution was dropped into an ionotropic gelling solution (polyphosphate and glutaraldehyde to form stable gel beads with improved porosity. The restriction of diffusion properties due to drying step was less drastic with the modified procedure: a few hours were sufficient for reaching equilibrium while more than two days were required for standard material

Osteoporosis and halo traction in scoliosis patients (author's transl)

In 54 patients who underwent halo traction for an average of 80 days each, there was no laboratory evidence of any change in calcium metabolism. Histologically, there were slight but significant bony changes after termination of halo traction treatment, principally "low-turnover" osteoporosis, which was possibly more prevalent in female patients. Where a slight osteoporosis already existed prior to halo traction, it generally became more severe. The study seems to show that no relationship exists between the etiology of scolioses and the development of osteoporosis. It proves that in respect of the development of osteoporosis also, permanent halo traction is not a neutral procedure.

Evaluating noise in social context: The effect of procedural unfairness on noise annoyance judgments

General dosage-response curves typically over- or underestimate the actual prevalence of noise annoyance for specific groups of individuals. The present study applies a social psychological approach to noise annoyance that helps to understand and predict collective deflections from the curve. The approach holds that being exposed to man-made sound is more than mere exposure; it is a social experience, too: You expose Me. In effect, social aspects of the situation, like the evaluation of the sound management procedure, influence the evaluation of sound. The laboratory experiment (N=90) investigates the effect of procedural unfairness on noise annoyance. The sound management procedure is varied systematically: Participants are promised they will listen to the sound of their choice (i.e., bird song, radio sound, or aircraft sound) but receive aircraft sound despite their expressed preference (unfair procedure), or they are simply told they will listen to aircraft sound (neutral procedure). All are exposed to aircraft sound (50 or 70 dBA Leq). A collective rise in noise annoyance is predicted in the unfair relative to the neutral procedure conditions. Results show that noise annoyance ratings are significantly higher in the unfair relative to the neutral conditions. Consequences for theory and practice are discussed.

AOAC Method 966.04: Preliminary Evaluation of Cooked Meat Medium with Manganese Sulfate for the Cultivation of Clostridium sporogenes: Precollaborative Study

AOAC Method 966.04, the Sporicidal Activity of Disinfectants Test, is a carrier-based test that provides a qualitative measure of product efficacy against spores of Bacillus subtilis and Clostridium sporogenes. For regulatory purposes, Method 966.04 is accepted by the U.S. Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration (FDA) for the generation of product performance data for sporicides and sterilants. In this study, we report on findings associated with proposed improvements (modifications) to the Clostridium component of the method. Egg meat medium (EMM), the culture medium for C. sporogenes currently specified in the method, is no longer commercially available and finding a suitable replacement is critical. In addition, the use of a nonstandardized extract of raw soil as an amendment to EMM, as stipulated in the current method, may result in a highly variable spore suspension. The primary focus of this study was to find replacements for EMM and soil extract. A carrier count procedure, the establishment of target carrier counts (spores/carrier), and a neutralization confirmation procedure were also evaluated. The study was limited to liquid products tested against Clostridium on a hard surface carrier (porcelain penicylinder). Spore suspensions of C. sporogenes were generated using: (1) EMM with soil extract (EMM/SE), (2) cooked meat medium with soil extract (CMM/SE), and (3) cooked meat medium with 5 microg/mL manganese sulfate (CMM/MnSO4). The titer of the spore suspension, carrier counts, resistance to hydrochloric acid (HCI), and efficacy against 3 liquid sporicidal agents were used to evaluate the potential of CMM and MnSO4 as replacements. The study was performed by the EPA Office of Pesticide Programs Microbiology Laboratory, Fort Meade, MD. Use of CMM/SE and CMM/MnSO4 resulted in comparable results for titer of spore suspensions (approximately 10(8) spores/mL) and carrier counts (approximately 3 x 10(6) spores/carrier). The carrier counts for the EMM/SE were approximately 1 log lower than CMM-based treatments; however, no attempt was made to dilute the CMM spore suspensions prior to carrier inoculation to reduce the carrier counts for CMM. Resistance of spores to 2.5 M HCI was acceptable across the 3 media types. Treatments for comparative efficacy testing were designed to provide a range of sporicidal activity, i.e., high and low efficacy treatments. Sodium hypochlorite (bleach), hydrogen peroxide/peracetic acid, and glutaraldehyde were used as test chemicals. The number of carriers resulting in growth (positive) for the low treatments for all 3 chemicals ranged from 9 to 59 out of 60 across the 3 media types--EMM exhibited fewer positives overall. The high efficacy treatments for sodium hypochlorite and hydrogen peroxide/peracetic acid yielded a range of 0 to 2 positives out of 60 across the 3 media. However, the high glutaraldehyde treatment generated 3, 20, and 20 positives out of 60 for the EMM/SE, CMM/SE, and CMM/MnSO4, respectively. The lower number of positive carriers for EMM/SE may be due to the reduced carrier counts. CMM, either with SE or MnSO4, appears to be a suitable replacement for EMM/SE. On the basis of the results of this study, the Study Director recommends that CMM/MnSO4 and the spore enumeration target carrier count and neutralization procedures be considered for collaborative study to officially modify the Clostridium x porcelain component of Method 966.04.

Contribution of the Heparin Neutralization Step to the Anti-PF4 ELISA.

The combination of anti-PF4 ELISA and serotonin release assay (SRA) has a reported sensitivity approximating 100% for diagnosing heparin-induced thrombocytopenia (HIT) - 7th ACCP Chest Supplement. Current therapeutic guidelines are to initiate therapy with a direct thrombin inhibitor (DTI) based on clinical parameters and to use HIT assays for diagnostic confirmation. Consequently, timely lab data may potentially minimize unnecessary drug exposure, reduce cost, and decrease morbidity. Due to test complexity, the ELISA results consistently precede the SRAs - the “gold standard” for HIT testing. This study examines the predictive value of the optical density (OD) reading and heparin neutralization procedure (100 IU/ml) for determining positive SRA. 200 patients with orders for the anti-PF4 ELISA (GTI) were retested with and without 100 IU of unfractionated heparin. Confirmation by heparin neutralization was reported as % inhibition (>50% inhibition = positive) as calculated by manufacturer's instructions.Negative SRAPositive SRANegative, OD/0.4342Positive, OD/0.412044The sensitivity and specificity of the ELISA was 95.6% and 21.6% respectively. The heparin neutralization step improved the specificity to 38.6% and did not alter the sensitivity. Figure 1 shows a single variable binary logistic regression analysis demonstrating the relationship between OD and probability for a positive SRA. An additional binary logistic regression analysis showed no statistical significance for the % neutralization with heparin. A receiver operators curve (ROC) (Figure 2)demonstrating an optimal sensitivity/specificity was generated for both the neat and the heparin neutralized samples. The curves were virtually identical with the same OD cut-off of 1.008. The specificity was nominally improved with the neutralization procedure. [Display omitted] [Display omitted] The heparin neutralization step only marginally improves the specificity of the anti-PF4 ELISA and does not correlate with a positive SRA result, and therefore, does not justify the added expense. Higher ELISA OD measurements correlate significantly with the probability of a positive SRA.

Increased Anti-Protein Z and Protein S Antibodies in Patients with Anti-Phospholipid Antibodies and/or Lupus Inhibitor.

Protein S (PS) and protein Z (PZ) are natural coagulation inhibitors that function as cofactors in mechanisms that decrease the generation of thrombin. Antibodies to PZ (aPZ) and PS (aPS) have been reported to be associated with adverse pregnancy outcomes (APO) and thrombosis (THRM). They have also been described in association with antiphospholipid antibodies (APLA) and the APLA syndrome (APLAS). We previously reported, ASH 2005, that there was an increase in aPZ and aPS in patients (pts) with serological and coagulation markers for APLA and lupus inhibitor (LI). In the current study we correlated the presence of aPZ and aPS in pts with APLA & LI with a THRM positive (+) or negative (−) history. We were not able to address the APO issue. The study group consisted of 26 male and 60 female, with ages ranging from 25 to 90, and mean age of 56. 33 pts are positive only for APLA (group 1) with 24 of them THRM(+), 16 pts are positive for LI only (group 2) with 7 of them THRM(+), and 37 pts are positive for both APLA and LI (group 3) with 21 of them THRM(+). The data was compared with 49 normal APLA/LI negative donors. We considered pts who have moderate to high levels of anticardiolipin and/or anti-β2 glycoprotein I (aB2GPI) as APLA positive. We define LI positive as pts with prolonged LI sensitive PTT, and positive for at least two of the confirmatory tests (Hexagonal phase assay, platelet neutralization procedure, and diluted Russel Viper Venom Time Ratio). THRM(+) included documented DVT, PE, stroke and TIA. We considered aPZ and aPS levels greater than 10 AU/ml as positive. Out data shows that in Group 1, statistically significant (SS) differences (p<0.05) between pts vs. the control group (CTR) were noted as increased (inc) aPZ IgG & IgM, and aPS IgM (aPZ IgG 5.1+/−9.3 vs 1.3+/−2.9AU/ml, aPZ IgM 20.6+/−43.9 vs 3.9+/−6.0AU/ml, aPS IgM 4.0+/−4.0 vs 1.0+/−1.2AU/ml). When compared THRM(+) vs CTR showed SS inc aPZ IgG, aPS IgM (aPZ IgG 6.0+/−10.7AU/ml, aPS IgM 3.9+/−3.0AU/ml). The 15 APLA patients with inc aPZ and/or aPS antibodies are all associated with positive aB2GPI IgM. In Group 2, SS differences (p<0.05) between pts vs. CTR were noted as inc aPS IgM (aPS IgM 3.2+/−4.0AU/ml). In Group 3, SS differences (p<0.05) between pts vs. CTR were noted as inc aPZ IgM and aPS IgM (aPZ IgM 16.5+/−25.5AU/ml, aPS IgM 3.0+/−5.3AU/ml). When compared THRM(+) vs CTR showed SS increased aPZ (aPZ IgM 19.8+/−31.9AU/ml). When compared THRM(−) vs CTR showed SS increased aPZ IgG & IgM and aPS IgM. (aPZ IgG 3.0+/−1.2AU/ml and IgM 12.5+/−15.5AU/ml, aPS IgM 2.1+/−1.6AU/ml). The 15 pts with elevated aPZ and/or aPS are also all associated with positive aB2GPI. However, two pts were positive for IgG subgroup instead IgM subgroup. Elevated aPZ IgG was only found in THRM(+) pts (11%). This would indicate that the inc aPZ IgG is associated with THRM. The 8 pts who had both inc aPZ and aPS antibodies were positive for THRM. Our data would indicate that aPZ and aPS antibodies might play a role in the prothrombotic state associated with APLAS. Our positive APLA group has a high % of inc aB2GPI-IgM. Does this affect the results in the THRM(+) group? Is the presence of IgM APLA more likely to be associated with aPS or aPZ? Does the combination of aB2GPI and inc aPS/aPZ have greater prognostic implications for THRM? Are there functional coagulation assays that might be used to determine the prothrombotic effect of the inc levels of aPZ and aPS antibodies?

Changes in Components of the Natural Coagulation Inhibitor System, in Patients with Antiphospholipid Antibodies and/or the Lupus Inhibitor.

The cell surface glycoproteins thrombomodulin (TM) and endothelial protein C receptor (EPCR) are major intermediaries in the down-regulation of thrombin and are noted to be shed from endothelial cells (ECs) due to the actions of proinflammatory cytokines, thrombin and other agents. Antiphospholipid antibodies (APLA) have been described as perturbing ECs. The level of protein S (PS) and protein Z (PZ) have been reported to inconsistently relate to the presence of antibodies and clinical outcomes. We previously reported using a coagulation assay system to demonstrate that adverse pregnancy outcomes (APO) are associated with a greater incidence of resistance to the anticoagulant effects of TM. In the current study we measured the plasma levels of soluble TM (sTM), soluble EPCR (sEPCR) as a possible indicator of APLA-EC interaction. We measured levels of free PS, PZ, sTM and sEPCR in patients (pts) with APLA and/or lupus inhibitor (LI), and correlated the findings with a positive or negative history for thrombosis [THRM(+) or (−)]. APO were not assessed at this time. The study group consisted of 26 males and 60 females, ages ranging from 25 to 90 years; mean of 56. GROUP 1: 33 pts with increased (inc) APLA and 24 of them THRM(+), GROUP 2: 16 pts positive for LI and 7 of them THRM(+), GROUP 3: 37 pts positive for both APLA & LI and 21 of them THRM(+). The pts were compared to 49 normal APLA negative donors (CTR). Pts who have moderate to high levels of anticardiolipin and/or anti-β2 glycoprotein I are APLA positive. LI positive pts have prolonged LI sensitive PTT, and are positive for at least two of the confirmatory tests (Hexagonal phase assay, platelet neutralization procedure, and diluted Russel Viper Venom Time Ratio). GROUP 1 has statistically significant (SS) (p<0.05) decreased (dec) sTM, sEPCR, and free PS when compared to CTR (sTM 1.0+/−1.4 vs 5.1+/−3.3ng/ml, sEPCR 43+/−53 vs 145+/−140ng/ml, free PS 63+/−25 vs 76+/−14%). Free PS is SS lower in the THRM(−) vs. THRM(+). PZ levels do not demonstrate SS differences in the subset comparisons. 8% of THRM(+) pts have PZ deficiency (PZ <1.0ug/ml) with none noted in the THRM(−) pts. Free PS is dec in a majority of the THRM(−). This might be related to the much higher % of females in the THRM(−). Therefore issues such as use of OCP, estrogens, current or recent pregnancy might influence PS. The incidents of dec sTM levels (<2.0ng/ml) are surprisingly higher in this group of patients (82%). This is strikingly higher than the CTR (4%). There is no apparent difference in the THRM(+) to THRM(−). The number of patients with dec sEPCR (<5ng/ml) is much lower however; none of the THRM(−) has dec levels. Inc sTM (>8.0ng/ml) nor inc sEPCR (>284ng/ml) is noted in any of the Pts. In GROUP 2, there is SS dec sTM & sEPCR (sTM 1.6+/−1.8ng/ml, sEPCR 42+/−32ng/ml) vs. CTR with no SS difference in the THRM(+) vs. THRM(−). In GROUP 3, sEPCR is SS dec in pts (sEPCR 68+/−100ng/ml) vs. CTR and CTR vs THRM(+) (sEPCR 29+/−25ng/ml). sTM is SS dec in the CTR vs. THRM(+) (sTM 1.3+/11.4ng/ml). Our data shows low levels of sTM and sEPCR in the APLA patients. This might indicate that the levels are consumed by antibody interactions and could indicate that the APLA and associated other antibodies might interfere with their functions. Previous reports indicating a resistance to TM in a coagulation assay method in patients with THRM and APO raises the possibility of an inhibiting substance present in the APLA. Further work in larger patient groups is necessary to clarify these issues.

A clean synthesis of polyhydroacridine and indenoquinoline derivatives catalyzed by triethylbenzylammonium chloride in aqueous media

Abstractmagnified imageAn efficient and convenient synthesis of benzo[a]acridines and indeno[1,2‐b]benzo[f]quinolines was achieved in high yields by the reaction of N‐arylidenenaphthalen‐2‐amine with 1,3‐dicarbonyl compounds catalyzed with triethylbenzylammmonium chloride (TEBAC) in aqueous media. The structures were established by spectroscopic data and further confirmed by X‐ray analysis. This method provides several advantages such as neutral conditions, high yields and simple work‐up procedure. In addition, water was chosen as a green and recyclable solvent.

Clean, One‐Pot Synthesis of Naphthopyran Derivatives in Aqueous Media

A general and practical one‐pot synthesis of naphthopyran derivatives using hexadecyltrimethylammonium bromide (HTMAB) as catalyst (10 mol%) is described. This method provides several advantages such as neutral conditions, high yields and simple workup procedure. The catalyst is low cost, facile, active, environmentally friendly, and reusable. In addition, water is chosen as a green solvent.

Clean synthesis of ethyl α-cyanocinnamates catalysed by hexadecyltrimethyl ammonium bromide in aqueous media

An efficient and convenient approach to the synthesis of ethyl α-cyanocinnamates in water using hexadecyltrimethyl ammonium bromide (HTMAB) as the phase-transfer catalyst (10 mol %) is described. This method provides several advantages such as neutral conditions, high yields and simple work-up procedure.

Characterization of TiO2 Nanoparticles in Langmuir-Blodgett Films

In this work we have synthesized TiO2 nanoparticles, using either a sol-gel base catalysed process in the interior of CTAB reversed micelles (TiO2 CTAB sol), or the neutralization of a TiO2/H2SO4 solution in the interior of AOT reversed micelles. From the absorption and emission data of the TiO2 nanoparticles it is possible to conclude that in the sol-gel route there remains alkoxide groups in the structure, originating transitions lower than the energy gap of TiO2 semiconductor. These transitions disappear in the neutralization procedure, where the alkoxide groups are absent in the structure. We have assigned the observed indirect and direct optical transitions according to the anatase band structure. TiO2 Langmuir-Blodgett (LB) films were prepared either by direct deposition of titanium isopropoxide or by deposition of the TiO2 CTAB sol. These films showed photoluminescence, which was attributed to band-gap emission and to surface recombination of defect states.

High Prevalence of Anti-Protein Z and Anti-Protein S Antibodies in Patients with Other Serological Markers for Antiphospholipid Antibodies.

Anti-protein Z (aPZ) and protein S (aPS) antibodies have been reported to be associated with adverse pregnancy outcome and thrombosis. We have studied the prevalence of aPZ and aPS antibodies in 63 patients who were referred to our laboratory for antiphospholipid antibody (APA) and lupus inhibitor (LI) evaluation, and 46 normal controls. We considered patients who have increased levels of anticardiolipin (ACL), anti-ß2 glycoprotein I (aB2GPI), or antiphosphatidyl-serine antibodies (aPSer) as APA positive. We define LI positive as patients with prolonged LI sensitive PTT (PTT-LA), and positive for any one of the confirmatory tests (Hexagonal phase assay, platelet neutralization procedure, and diluted Russel Viper Venom Time Ratio). 27 of the 63 patients have APA, 24 of the 63 patients have LI, and 12 of the 63 patients have both APA and LI. Table 1 shows the means and standard deviation (SD) of aPS and aPZ levels of the 63 patients compared to the 46 normal controls. The means aPZ IgM for the total 63 patients group and the 27 patients with APA alone are statistically significantly greater than the control group (p<0.05). We considered aPZ and aPS levels greater than the normal control mean plus 2 SD as positive (aPZ IgG>2.32, IgM>2.95, aPS IgG>3.18, IgM>5.8). Of the 63 patients, 7 (11%) are positive for aPZ IgG, 22 (35%) positive for aPZ IgM, 4 (6%) positive for aPS IgG, and 4 (6%) positive for aPS IgM. In the aPZ, IgG and IgM, positive patients (N=28), 9 (32%) are LI only, 16(57%) are APA only, and 3 (11%) have both LI and APA. Of the 16 APA only, 13 have ACL, 11 have aPSer, and 8 have aB2GPI. For the aPS positive group, 4 positive IgG patients have APA only, and 4 positive IgM patients have LI only. We also have three additional patients other than the 63 patient, who have increased anti-prothrombin antibodies present. These three patients have high aPS IgM antibody (mean 4.50 +/− 3.16). In conclusion, we have found that aPZ IgM antibody are higher in the patients with serological markers for APA and LI compared to our normal controls. We also found that a substantial minority of our patients have increase aPZ (46%) and aPS (13%) antibodies. Since these antibodies have been reported to be associated with thrombosis and adverse pregnancy outcome they may have prognostic implications in those patients with serological markers for APA and LI. We also noticed that high percentage of our aPZ and aPS positive patients have LI. Our data would suggest the inclusion of these antibodies in the evaluation for immune related prothrombotic states and adverse pregnancy outcome. However, larger population study with detailed clinical information and patient outcomes are needed to make appropriated recommendations as to the efficacy for this type of laboratory testing.Mean aPS and aPZ levels of the 63 patients and 46 controlsCTR (N=46)All patients (N=66)APA only (N=30)LI only (N=24)APA + LI (N=12)aPZ IgG0.50 +/− 0.911.01 +/− 2.280.92 +/− 1.081.20 +/− 3.520.84 +/− 0.58aPZ IgM0.99 +/− 0.982.83 +/− 2.96*3.07 +/− 2.0*2.21 +/− 3.663.52 +/− 3.24*aPS IgG0.64 +/− 1.270.84 +/− 1.081.22 +/− 1.470.35 +/− 0.290.98 +/− 0.6aPS IgM2.02 +/− 1.892.51 +/− 3.522.22 +/− 1.302.93 +/− 5.452.30 +/− 1.77* vs CTR P<0.05

Presence of Direct Thrombin Inhibitors Can Affect the Results and Interpretation of Lupus Anticoagulant Testing

In vitro experiments were conducted to determine whether the direct thrombin inhibitors argatroban and lepirudin can interfere with the results of lupus anticoagulant (LA) testing. Concentration-response curves were generated to calculate the concentration of anticoagulant that prolongs the activated partial thromboplastin time (aPTT) to 75 seconds (2.5 times the baseline average). Corresponding concentrations of anticoagulant were added to plasma samples before running dilute Russell viper venom time (DRVVT) and LA-sensitive aPTT (PTT-LA) tests. Because the DRVVT test system contains an antiheparin agent, DRVVT results were not prolonged in the presence of heparin. With argatroban added to normal plasma samples, neither the DRVVT percent correction of ratio nor the DRVVT test/confirm ratio was elevated, but when added to LA-positive plasma, some false-negative results were observed. Lepirudin increased the DRVVT percent correction of ratio and the DRVVT test/confirm ratio into a range that could lead to false-positive identifications of LAs. In sharp contrast to the DRVVT test system, distinction between LA-positive and LA-negative plasma samples was maintained and possibly even enhanced in the platelet neutralization procedure correction phase of the PTT-LA test system.

Presence of Direct Thrombin Inhibitors Can Affect the Results and Interpretation of Lupus Anticoagulant Testing

In vitro experiments were conducted to determine whether the direct thrombin inhibitors argatroban and lepirudin can interfere with the results of lupus anticoagulant (LA) testing. Concentration-response curves were generated to calculate the concentration of anticoagulant that prolongs the activated partial thromboplastin time (aPTT) to 75 seconds (2.5 times the baseline average). Corresponding concentrations of anticoagulant were added to plasma samples before running dilute Russell viper venom tests (DRVVTs) and LA-sensitive aPTTs (PTT-LAs). Because the DRVVT test system contains an antiheparin agent, DRVVT results were not prolonged in the presence of heparin. With argatroban added to normal plasma samples, neither the DRVVT percent correction of ratio nor the DRVVT test/confirm ratio were elevated, but when added to LA-positive plasma, some false-negative results were observed. Lepirudin increased the DRVVT percent correction of ratio and the DRVVT test/confirm ratio into a range that could lead to false-positive identifications of LAs. In sharp contrast to the DRVVT test system, distinction between LA-positive and LA-negative plasma samples was maintained and possibly even enhanced in the platelet neutralization procedure correction phase of the PTT-LA test system.

Clean Synthesis of Compounds Containing Two 4H‐Pyrans or Two Tetraketones in Aqueous Media

A general and practical chemistry route to the synthesis of compounds containing two 4H‐pyrans or two tetraketones in aqueous media is described. This method provides several advantages such as neutral conditions, high yields, and simple workup procedure. In addition, water was chosen as a green solvent.

McDowell and habermas in a Post-Traditional World

John McDowell indicts modern philosophy's contrast between the "space of reasons" and the "organization of nature."1 He challenges this framework as a limitation of options-meanings marked off from causes, mind segregated from world-and outlines an alternative, which draws upon Aristotle's ethics. McDowell's reading of Aristotle avoids this "distinctively modern" anxiety, by demonstrating a different conception of what is natural. Aristotle's "practical wisdom" serves as a model for how we come to understand, how our experiences become intelligible and are placed in the "space of reasons." For Aristotle, "virtue" is distinguished from mere habit and responds to reason but this response is never completely severed from habitual ways of living. Therefore it brings into view what McDowell means by "naturalism," wherein the duality between natural laws and rational justification is eliminated. This reconciliation rejects the tension that pits a "bald naturalism" against a "rampant platonism" and not only diagnoses but, in Mc Dowell's view, "cures" the anxiety of modern philosophy-one from which Aristotle and his contemporaries did not suffer. "The picture is that ethics involves requirements of reason that are there whether we know it or not, and our eyes are opened to them by the acquisition of a 'practical wisdom.'"2 This, for McDowell, exemplifies a "second nature." Habermas, too, acknowledges ways in which the intentions of modernity have been fractured and have gone astray. However, unlike McDowell, he sees modernity's "cognitive potentials" as a way to correct "a life praxis still dependent on blind traditions."3 He insists that moral statements can be justified, therefore must have cognitive content-and that this content approaches an "ethically neutral" form (ethical, for Habermas, refers to local decisions about the everyday "good life") for "decentered" individuals and societies. Such recognition of norms that supercede the parochial in a post-traditional pluralistic world is imperative for Habermas. "In the absence of substantive agreement on particular norms, the participants must now rely on the 'neutral' fact that each of them participates in some communicative form of life which is structured by linguistically mediated understanding."4 Here Habermas follows the lead of Hegel, Humboldt, and Mead in philosophy, speechact theorists in linguistic pragmatics, Piaget and Kohlberg in moral psychology, and the historicist perspective of two of his own teachers, Gadamer and Adorno. He expands and interweaves these theories into a strong cognitivist argument for the possibility of context-transcendent moral validity claims. Habermas's writings contain only rare engagements with McDowell and McDowell has none with Habermas. Habermas's few references reveal intense skepticism as to whether McDowell's moral theory, which Habermas categorizes as weak cognitivism, is sufficient to explain how reliance on Aristotelian "practical reason," even though there is a role for "insight," can ever rise above particular forms of life-a feature of morality so necessary in a post-metaphysical world. Once questions of justice arise across cultures, sub-cultures, or nations, such neo-Aristotelian views reveal their limitations for maintaining the "absolute priority of the right over the good . . . [and] fall short of the universalistic content of a morality of equal respect and solidaristic respect for everyone."5 While there are surprising similarities in the "relaxed naturalisms" of Habermas and McDowell, Habermas's stronger form of cognitivism reduces a tension in McDowell's argument regarding the relationship between "potentialities" and "upbringing" (Bildung). In fact, McDowell's weak cognitivism is never convincing as to why one moral language game is superior to another. Like other neo-Aristotelian standpoints, it doesn't transcend community in the way Habermas's "formal pragmatics" provides a neutral procedure to adjudicate conflict. …

A Case of IgM- λ Waldenström's Macroglobulinemia with Activity Against Phospholipids, Masquerading as Factor V Inhibitor.

Background: The Lupus anticoagulant is known to prolong coagulation tests, however the source of antibody causing this prolongation is not clear in the majority of patients. We are reporting a patient with prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) secondary to a lupus anticoagulant like activity of an IgM paraprotein.Case report: An 82 years old male patient was referred in January 1996 to our clinic for abnormal PT and aPTT. He was asymptomatic. There was no lymphadenopathy or organomegaly. The hemoglobin was 10.4 (g/dl) with normal white cell and platelet count. Renal and liver function tests were normal. Coagulation studies revealed aPTT 145.4 seconds, the PT 38.8 seconds, thrombin time 24.9 seconds, fibrinogen level of 336 mg/dl and D Dimer <500. In-vitro mixing studies with normal plasma failed to correct the prolongation of the clotting tests without and with incubation for 1 hour. This suggested the presence of an inhibitor. Factor inhibitor assays were done that suggested the presence of a factor V inhibitor (14.8 Bethesda units). The apparent lower level inhibitory activity against other factors II, VII and X was presumed to be due to inhibition of prothrombinase complex by factor V inhibitor. Agarose affinity column chromatography with factor V bound to the agarose did not remove the PT inhibitory activity. A lupus anticoagulant was suspected when the PT and aPTT of normal pooled plasma was prolonged by the addition of patient's plasma. The patient's plasma with pooled normal plasma gave a positive dilute thromboplastin inhibition test, 1:50 dilution >3.1 and 1:500 dilution >2.9 (normal <1.3) as well as a positive PNP (platelet neutralization procedure) as evidenced by a shortening of aPTT from >106 seconds to 48 seconds upon the addition of platelet phospholipids (a difference of >5 sec is taken as positive for LA). Expanded antiphospholipid antibodies test were done. Anti-cardiolipin IgM (>100MPL), anti-phosphotidyl serine IgM (7.3SD) were detected. A serum protein electrophoresis revealed monoclonal gamma spike of approximately > 4gm/dl and quantitative immunoglobulin by radial immuno-diffusion (RID) showed IgG- 1691 mg/dl, IgA - 185 mg/dl, IgM >192 mg/dl. The IgM >192 mg/dl is limited by the linearity of the test. IFE (Immunoelectrophoresis) demonstrated IgM-λ spike. Serum viscosity was 3.4. We suspected that the IgM paraprotein might be the inhibitor. IgM was purified by Euglobulin flocculation test. The PT and aPTT of normal pooled plasma was prolonged on its addition. The conclusion was that antiphospholipid activity was in IgM. Bone marrow biopsy in January 1996 showed <10% of plasmacytoid lymphocytes. Repeat bone marrow biopsy in December 1997 showed increased plasmacytoid cells to 60%. In view of increased serum viscosity to 4.3 and bone marrow biopsy findings as above, a diagnosis of progressive Waldenström's Macroglobulinemia was established. In addition to intermittent plasmapheresis, an oral chlorambucil (0.25mg/kg) q21 day was given for 14 months from December 1997, with a decrease in paraproteins, serum viscosity and PT, aPTT. Patient remained asymptomatic till March 2002 when he developed clinically progressive disease as evidenced by hepatosplenomegaly. He refused all investigations and interventions at this time and was lost to follow up. During the entire follow up period lasting 6 years he did not demonstrate any bleeding or thrombotic tendency.

The prevalence of lupus anticoagulant in normal pregnancy and in women with recurrent fetal loss—recommendations for laboratory testing for lupus anticoagulant

BACKGROUNDThere is wide disagreement in the literature on the rate of detection of lupus anticoagulant (LA) in women with recurrent fetal loss (RFL). The aim of this study was to determine the prevalence of LA using four phospholipid-dependant coagulation tests in a large population of Saudi women.PATIENTS AND METHODSWe determined the prevalence of LA in women with RFL (n=925), normal pregnancy (n=663), and in healthy blood donors (n=204), at the King Khalid University Hospital, Riyadh. The following coagulation tests were employed: the activated partial thromboplastin time (APTT), platelet neutralization procedure (PNP), kaolin clotting time (KCT) and the dilute Russel's viper venom test (dRVVT).RESULTSIn RFL patients, positive APTT was 10.2%, APTT+PNP 3.6%, KCT 10.5%, and dRVVT 10.9%. In normal pregnancy, the corresponding figures were 12.8%, 3.1%, 10.8%, and 5.6%. Three positive tests occurred in 2.3% of RFL patients, including APTT+KCT 3.5%, APTT+dRVVT 3.9%, and KCT+dRVVT 4.1%. The corresponding figures for normal pregnancy were 1.6% for three positive tests, and 3.0%, 1.8%, 2.4%, respectively. The dRVVT was the only test that showed a rate of positive results almost double that seen in normal pregnancy.CONCLUSIONSIf only one or even two screening tests were performed, a significant number of LA positive cases would have been missed. This could make a difference to treating physicians as to the possible etiology and management of RFL. It is therefore advisable to routinely use the three tests (APTT, KCT and dRRVT) when screening for LA.

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.