Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin

IntroductionAirway fluid glutathione (GSH) reactivity with inhaled vapors of diisocyanate, a common occupational allergen, is postulated to be a key step in exposure-induced asthma pathogenesis.MethodsA mixed (vapor/liquid) phase exposure system was used to model the in vivo reactivity of inhaled HDI vapor with GSH in the airway fluid. HDI–GSH reaction products, and their capacity to transfer HDI to human albumin, were characterized through mass spectrometry and serologic assays, using HDI-specific polyclonal rabbit serum.ResultsHDI vapor exposure of 10 mM GSH solutions resulted in primarily S-linked, bis(GSH)–HDI reaction products. In contrast, lower GSH concentrations (100 μM) resulted in mainly mono(GSH)–HDI conjugates, with varying degrees of HDI hydrolysis, dimerization and/or intra-molecular cyclization, depending upon the presence/absence of H₂PO₄^?/HPO₄^2? and Na⁺/Cl^? ions. The ion composition and GSH concentration of the fluid phase, during HDI vapor exposure, strongly influenced the transfer of HDI from GSH to albumin, as did the pH and duration of the carbamoylating reaction. When carbamoylation was performed overnight at pH 7, 25 of albumin’s lysines were identified as potential sites of conjugation with partially hydrolyzed HDI. When carbamoylation was performed at pH 9, more rapid (within 3 h) and extensive modification was observed, including additional lysine sites, intra-molecular cross-linkage with HDI, and novel HDI–GSH conjugation.ConclusionsThe data define potential mechanisms by which the levels of GSH, H₂PO₄^?/HPO₄^2?, and/or other ions (e.g. H⁺/OH^?, Na⁺, Cl^?) affect the reactivity of HDI vapor with self-molecules in solution (e.g. airway fluid), and thus, might influence the clinical response to HDI respiratory tract exposure.     

Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases

Purpose

To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival.

Methods

A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases in 2009 and 2010 at a tertiary referral center. Variables related to postoperative survival were all included in the same multivariable logistic regression analysis with either 3- or 12-month survival as the dependent variable. The independent variables were: transfusion of allogenic red blood cells, age at surgery, gender, preoperative hemoglobin, revised Tokuhashi score and no. of instrumented levels.

Results

Perioperative allogenic blood transfusion of 1–2 units was associated with increased 12-month survival [p = 0.049, odds ratio 2.619 (confidence interval 1.004–6.831)], but not with 3-month survival. Larger transfusion volumes did not significantly influence survival.

Conclusion

The results of the present study support that perioperative blood transfusion of <5 units does not decrease survival in patients operated for spinal metastases. Transfusion of 1–2 units seems to be associated with increased 12-month survival. Future studies should assess if a liberal transfusion regime can be applied to this group of patients; thereby, prioritizing early postoperative mobilization.     

Central nervous system disease in primary Sjogrens syndrome: the role of magnetic resonance imaging

OBJECTIVES: To examine the frequency of central nervous system (CNS) disease in primary Sjogrens syndrome (pSS) and indicate ways in which cerebral magnetic resonance imaging (MRI) may help determine the significance of CNS involvement. METHODS: The current review was based on a Medline (Pubmed) literature search through May 2003, focused on Sjogrens syndrome, other vasculitides, multiple sclerosis (MS), specific MRI techniques, and MRI findings with regard to the above-mentioned diseases. Additional literature was identified in the reference sections of articles listed in Medline. RESULTS: Severe CNS manifestations reminiscent of MS have been described in pSS patients. Moreover, the prevalence of nonfocal neuropsychological abnormalities has been found to be elevated in some pSS patient populations. MRI studies suggest discrete cerebral tissue damage even in neurologically asymptomatic patients. However, small white matter lesions are nonspecific and may be related to age or cerebrovascular risk factors such as hypertension. A large controlled study, complementing established T2-weighted MRI with fluid-attenuated inversion recovery (FLAIR) to achieve high sensitivity in lesion detection, could indicate the disease specificity of white matter lesions in pSS. Newer MR techniques, such as spectroscopy and magnetization transfer imaging, applied, for example, in MS and systemic lupus erythematosus (SLE) to evaluate CNS tissue injury, could help determine the extent and mechanisms of macroscopic and microscopic CNS lesions in pSS. CONCLUSIONS: Future controlled studies will be necessary to more precisely estimate the prevalence of CNS lesions in pSS, specifically of discrete white matter abnormalities. Newer MRI techniques have the potential to provide information on the severity and pathophysiological mechanisms of CNS tissue damage.     

Ring-enchancement in multiple sclerosis: marker of disease severity

Correlations between conventional MRI measures of disease activity and clinical disability in multiple sclerosis (MS) have been disappointing. Because ring-enhancing lesions may reflect a more destructive pathology, we tested their potential association with disease severity. We evaluated active lesions with regard to their enhancement pattern on serial magnetic resonance images in a cohort of 28 patients with relapsing-remitting MS. The percentage of ring-enhancing lesions correlated with EDSS, T2 lesion load and duration of disease and predicted the occurrence of relapses during the baseline period of observation as well as after 3 years of follow-up in multiple logistic regression analysis. The findings suggest that the pathological process reflected by ring-enhancing lesions may contribute to more severe clinical disease.     

Cefoxitin for one dayvs. ampicillin and metronidazole for three days in elective colorectal surgery

In a multicenter study the prophylactic efficacy of two antibiotic regimens was tested against postoperative septic complications following elective colorectal surgery. The study was conducted in a prospective block-randomized design. Patients were preoperatively allocated to either ampicillin, 1 gm, four times daily, and metronidazole, 0.5 gm, three times daily, for 72 hours, or to cefoxitin, 2 gm, given three times in a period of 10 hours. Both regimens were initiated immediately before surgery. Forty-five patients were withdrawn from the study after randomization. Three hundred fifty two patients (175 receiving ampicillin and metronidazole and 177 receiving cefoxitin) completed the study and were followed for one month postoperatively. The frequency of septic and nonseptic complications was not statistically significant different between the two regimens. About one third of all septic complications appeared more than two weeks after surgery. It is concluded that short-term treatment with cefoxitin is at least as efficient as a three-day treatment with ampicillin and metronidazole.