Predictive model for estimating risk of crush syndrome: a data mining approach

BACKGROUND: There is no standard triage method for earthquake victims with crush injuries because of a scarcity of epidemiologic and quantitative data. We conducted a retrospective cohort study to develop predictive models based on clinical data for crush injury in the Kobe earthquake. METHODS: The medical records of 372 patients with crush injuries from the Kobe earthquake were retrospectively analyzed. Twenty-one risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome. Two types of predictive triage models--initial evaluation in the field and secondary assessment at the hospital--were developed using logistic regression analysis. Classification accuracy, Brier score and area under the receiver operating characteristic curve (AUC) were used to evaluate the model. RESULTS: The initial triage model, which includes pulse rate, delayed rescue, and abnormal urine color, has an AUC of 0.73. The secondary model, which includes WBC, tachycardia, abnormal urine color, and hyperkalemia, shows an AUC of 0.76. CONCLUSIONS: These triage models may be especially useful to nondisaster experts for distinguishing earthquake victims at high risk of severe crush syndrome from those at lower risk. Application of the model may allow relief workers to better utilize limited medical and transportation resources in the aftermath of a disaster.     

Isolation and structure determination of oxidative degradation products of atorvastatin

Methods were developed for the preparation and isolation of four oxidative degradation products of atorvastatin. ATV-FX1 was prepared in the alkaline acetonitrile solution of atorvastatin with the addition of hydrogen peroxide. The exposition of aqueous acetonitrile solution of atorvastatin to sunlight for several hours followed by the alkalization of the solution with potassium hydroxide to pH 8–9 gave ATV-FXA. By the acidification of the solution with phosphoric acid to pH 3 ATV-FXA1 and FXA2 were prepared. The isolation of oxidative degradation products was carried out on a reversed-phase chromatographic column Luna prep C18(2) 10 μm applying several separation steps. The liquid chromatography coupled with a mass spectrometer (LC-MS), high resolution MS (HR-MS), 1D and 2D NMR spectroscopy methods were applied for the structure elucidation. All degradants are due to the oxidation of the pyrrole ring. The most probable reaction mechanism is intermediate endoperoxide formation with subsequent rearrangement and nucleophilic attack by the 5-hydroxy group of the heptanoic fragment. ATV-FX1 is 4-[1b-(4-Fluoro-phenyl)-6-hydroxy-6-isopropyl-1a-phenyl-6a-phenylcarbamoyl-hexahydro-1,2-dioxa-5a-aza-cyclopropa[a]inden-3-yl]-3-(R)-hydroxy-butyric acid and has a molecular mass increased by two oxygen atoms with regard to atorvastatin. ATV-FXA is the regioisomeric compound, 4-[6-(4-Fluoro-phenyl)-6-hydroxy-1b-isopropyl-6a-phenyl-1a-phenylcarbamoyl-hexahydro-1,2-dioxa-5a-aza-cyclopropa[a]inden-3-yl]-3-(R)-hydroxy-butyric acid. Its descendants ATV-FXA1 and FXA2 appeared without the atorvastatin heptanoic fragment and are 3-(4-Fluoro-benzoyl)-2-isobutyryl-3-phenyl-oxirane-2-carboxylic acid phenylamide and 4-(4-Fluoro-phenyl)-2,4-dihydroxy-2-isopropyl-5-phenyl-3,6-dioxa-bicyclo[3.1.0]hexane-1-carboxylic acid phenylamide, respectively. Quantitative NMR spectroscopy was employed for the assay determination of isolated oxidative degradation products. The results obtained were used for the determination of the UV response factors relative to atorvastatin.     

Radiation exposure of hemophiliacs after radiosynoviorthesis with 186Re colloid

Very limited data are available in the literature on the doses of unwanted radiation that patients receive following treatment with radiosynoviorthesis (RSO). OBJECTIVE: The aim of this study was to assess the radiation exposure after RSO with (186)Re colloid in hemophiliacs. METHODS: This study involved 12 hemophiliacs who were treated for hemophilic joint disease with 14 RSOs by using (186)Re colloid. Whole-body scintigrams were performed 1, 6, and 24 hours and 3 and 7 days after RSO. Measurements, using a whole-body counter, were done immediately after scintigraphy, with the treated joint protected with a lead shield. The cumulative activity of (186)Re in the body and in the lymph nodes was calculated. The distribution of (186)Re in the body was determined by using the values for small colloids as proposed by the International Commission on Radiological Protection (ICRP) Publication 53. The computer code, OLINDA/EXM (Vanderbilt University, Nashville, TN), was used for the calculation of the internal dose. A constant distance of 1 m between the ankle joint and body organs, and of 0.33 m between the elbow or shoulder joint and body organs, was used to calculate the contribution of gamma radiation to the effective radiation dose. RESULTS: The mean effective dose received by hemophiliacs after RSO with (186)Re colloid was 28 +/- 9 microSv/MBq of the activity injected into the joint. The patients received 0.8-3.7 mSv (1.9 +/- 0.8 mSv) owing to the leakage of (186)Re from the treated joint and its retention in the body. The highest doses were established in the spleen (26.0 +/- 10.7 mGy), the liver (17.6 +/- 7.2 mGy), and red marrow (3.0 +/- 0.8 mGy). The contribution of gamma radiation to the effective dose was less than 0.1 mSv in RSO of the ankle, 0.4 mSv in the elbow, and 0.6 mSv in the shoulder-joint treatment. The activity of (186)Re in the regional lymph nodes was noted in 4 of the 14 treatments. In these cases, the estimated average dose received by individual lymph nodes was 14.7 +/- 1.9 Gy. CONCLUSIONS: RSO with (186)Re colloid is a safe treatment method. The effective dose received by patients after RSO by using (186)Re colloid is low, as are the radiation doses to the most exposed organs. If (186)Re is retained in the regional lymph nodes, the lymph node radiation dose would be high.     

Role of ultrasound in the preoperative staging of patients with breast cancer

The aim of this study was to evaluate the ability of axillary ultrasound (US) and US-guided fine-needle aspiration biopsy (FNAB) to detect axillary LN metastases. Between January 2001 and September 2003, axillary US was performed in 165 patients with cytologically or histologically proven breast cancer and clinically non-palpable axillary LNs. In patients with US suspicious LNs, US-guided FNAB was performed and patients with cytologically proven malignant LNs proceeded directly to the ALND. In 49/90 patients with US suspicious LNs, US-guided FNAB was performed. It was positive in 33/49 patients. Definitive histology report revealed LN metastases in 65/165 patients. The sensitivity, specificity, positive and negative predictive value of the US-FNAB, were 84, 91, 97 and 62%. Axillary US in a combination with US-FNAB is a valuable method in preoperative staging of patients with breast cancer. Almost 50% of patients with LN metastases can be spared the second operation. However, it is very much operator-dependent and equipment-dependent.     

Design, synthesis, biochemical evaluation and antimycobacterial action of phosphonate inhibitors of antigen 85C, a crucial enzyme involved in biosynthesis of the mycobacterial cell wall

Phosphonate inhibitors of antigen 85C were prepared. The inhibitors, comprising a phosphonate moiety, mycolic acid mimetic and a trehalose surrogate, contain substituted benzyl alcohols, N-(omega-hydroxyalky)phthalimide, 2-phenylethanol or 4-(phthalimido)butanol as trehalose mimetics, and an alkyl chain of different lengths mimicking the mycolic acid side chain. The best compounds inhibited the mycolyltransferase activity of antigen 85C with IC(50) in the low micromolar range and inhibited the growth of Mycobacterium avium in culture. The best compounds in the 3-phenoxybenzyl- and omega-(phthalimido)alkoxy series, ethyl 3-phenoxybenzyl butylphosphonate (4a) and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl ethyl heptylphosphonate (5c) displayed IC(50) values of 2.0 and 1.3 microM, respectively, in a mycolyltransferase inhibition assay. In a M. avium growth inhibition assay MIC of 4a and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl ethyl nonylphosphonate (5d) were 248.8 and 84.5 microg/mL, respectively.     

Cell membrane integrity and internalization of ingested TiO(2) nanoparticles by digestive gland cells of a terrestrial isopod

The present study was motivated by the paucity of reports on cellular internalization of ingested titanium dioxide (TiO(2)) nanoparticles (nano-TiO(2)). The model invertebrate (Porcellio scaber, Isopoda, Crustacea) was exposed to food dosed with nano-TiO(2) containing 100, 1,000, 3,000, or 5,000?μg nano-TiO(2) per gram of food. After 14?d of exposure, the amount of Ti in the entire body was analyzed by inductively coupled plasma-mass spectrometry, and elemental analyses of tissue cross sections were performed by particle induced X-ray emission. In addition, a series of toxicological markers including feeding parameters, weight change, and survival, as well as cytotoxic effects such as digestive gland cell membrane stability, were monitored. Internalization of ingested nano-TiO(2) by the isopod's digestive gland epithelial cells was shown to depend on cell membrane integrity. Cell membranes were found to be destabilized by TiO(2) particles, and at higher extracellular concentrations of nano-TiO(2), the nanoparticles were internalized.