Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4, south-western France, June 2011.

Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south-western France, household transmission due to Escherichia coli O104:H4 was suspected for two cases who developed symptoms 9 and 10 days after onset of symptoms of the index case. The analysis of exposures and of the incubation period is in favour of a secondary transmission within the family. Recommendations should be reinforced to prevent person-to-person transmission within households.

Parametric and quantitative analysis of MR renographic curves for assessing the functional behaviour of the kidney.

The aim of this study was to refine the description of the renal function based on MR images and through transit-time curve analysis on a normal population and on a population with renal failure, using the quantitative model of the up-slope. Thirty patients referred for a kidney MR exam were divided in a first population with well-functioning kidneys and in a second population with renal failure from ischaemic kidney disease. The perfusion sequence consisted of an intravenous injection of Gd-DTPA and of a fast GRE sequence T1-TFE with 90 degrees magnetisation preparation (Intera 1.5 T MR System, Philips Medical System). To convert the signal intensity into 1/T1, which is proportional to the contrast media concentration, a flow-corrected calibration procedure was used. Following segmentation of regions of interest in the cortex and medulla of the kidney and in the abdominal aorta, outflow curves were obtained and filtered to remove the high frequency fluctuations. The model of the up-slope method was then applied. Significant reduction of the cortical perfusion (Qc = 0.057+/-0.030 ml/(s 100 g) to Qc = 0.030 +/- 0.017 ml/(s 100 g), P < 0.013) of the medullary perfusion (Qm = 0.023 +/- 0.018 ml/(s 100 g) to Qm = 0.011 +/- 0.006 ml/(s 100 g), P < 0.046) and of the accumulation of contrast media in the medulla (Qa = 0.005 +/- 0.003 ml/(s 100 g) to Qa = 0.0009 +/- 0.0008 ml/(s 100 g), P < 0.001) were found in presence of renal failure. High correlations were found between the creatinine level and the accumulation Qa in the medulla (r2 = 0.72, P < 0.05), and between the perfusion ratio Qc/Qm and the accumulation Qa in the medulla (r2 = 0.81, P < 0.05). No significant difference was found in times to peak between both populations despite a trend showing Ta the time to the end of the increasing contrast accumulation period in the medulla, arriving later for renal failure. Advances in MR signal calibration with the building of quantitative model such as the up-slope allow to assess kinetic and haemodynamic and functional parameters of the diseased kidney.

Sulfur derivatives of 2-oxopropanal oxime as reactivators of organophosphate-inhibited acetylcholinesterase in vitro: synthesis and structure-reactivity relationships.

We have prepared four new oximes, 1b-e, which conform to the general structure RCH2COCH = NOH where R = CH3S, CH3SO, CH3SO2, and (CH3)2S+, respectively, and have the same E configuration as the parent 2-oxopropanal oxime 1a (R = H, MINA). The pKa values range from 6.54 (1e) to 8.16 (1b), as compared with 8.30 for 1a. Rates of reaction (kappa 1) with 4-nitrophenyl acetate indicate that the oximate anions have a much higher nucleophilicity than common oxyanions of similar basicities: the alpha effects measured for 1a-e are of the order of 200-250. The abilities of 1b-e to reactivate acetylcholinesterase (AChE) inhibited by organophosphates have been evaluated. In vitro experiments reveal a significant reactivation potency of 1b-e against VX-, sarin-, and paraoxon-inhibited immobilized eel AChE. The highly lipophilic methylthio oxime 1b (log P greater than 1) is intrinsically (kappa 2) 3 times more reactive than the more basic MINA (log P less than 1). The sulfonium oxime 1e is a potent reactivator against paraoxon. Interestingly, both 1b and 1e have a low toxicity and they exhibit a significant antidotal effect at a relative low dose against paraoxon in rats.

Edema and the lack of blood perfusion produce opposite effects on the magnetic resonance characteristics of acutely ischemic rat kidneys.

Both kidneys of 28 rats were studied with magnetic resonance imaging (0.35 tesla, double spin-echo technique with echo-delay times [TEs] of 28 and 56 ms and repetition times [TRs] of 0.5 and 2.0 seconds). Kidneys were studied before and up to 4 hours after ligation of the abdominal aorta above the origin of the left renal artery (20 rats) or after ligation of the left renal artery (eight rats). Any changes in the relaxation times of cortex and medulla and in the cortex-to-medulla contrast (CMC) were correlated to histologic data and renal water content. After the first hour following ligation of either the abdominal aorta or the left renal artery, the cortex of the left kidneys showed a 20% shortening of the mean T2 relaxation time (P less than .001), a 16% shortening of the mean T1 relaxation time (P less than .001), a 73% increase in mean CMC on T2-weighted images (P less than .001) and a 42% decrease in mean CMC on T1-weighted images (P less than .001). There were no significant changes either in relaxation times of the medulla of the left kidneys or in relaxation times and CMC of the right kidneys. During the next three hours, relaxation times of cortex and CMC remained unchanged in the rats with ligated abdominal aorta. In the rats with ligated renal artery, relaxation times of cortex and CMC returned to normal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate mapping in ischemic rat kidneys using 1H spectroscopic imaging.

RATIONALE AND OBJECTIVES: Biochemical studies have shown that during renal ischemia, lactate is built up predominantly in the medulla and less in the cortex. The authors intend to confirm such a difference in lactate concentration between these two zones of the kidney by means 1H magnetic resonance (MR) spectroscopy. METHODS: In 10 rats, the authors used four-dimensional (n = 4) and three-dimensional (n = 6) spectroscopic imaging to investigate the left kidney after occlusion of the renal artery. RESULTS: By this technique, a map of the intrarenal lactate distribution was obtained during ischemia. It was determined that lactate concentration is indeed higher in the medulla than in the cortex, as verified by chemical analysis (17 +/- 4 versus 9 +/- 4 mumol/g). CONCLUSIONS: By correlating biochemical and morphologic information, localized MR spectroscopy combined with imaging is a powerful tool for investigating pathophysiologic mechanisms.

Magnetic resonance imaging of experimental renal hemorrhage.

Experimental renal hemorrhage was induced by injecting autologous blood into the left kidney of 13 rats. To investigate the magnetic resonance (MR) characteristics of acute renal hemorrhage and subsequent stages of resolution, repetitive MR images were obtained using a 0.35 Tesla imager during a period of 21 days postinduction. A dual spin-echo imaging (TR 500 and 2,000 msec, TE 28 and 56 msec) was used to calculate the relaxation times and record the intensities in the renal medulla and cortex. Histologic examination (n = 9) indicated that blood was dispersed intrarenally, and no encapsulated hematoma developed. The signal intensity on the T1- and T2-weighted images, as well as the relaxation times in the hemorrhagic renal parenchyma were unchanged during 21 days when compared with intact kidney values. Subcapsular fresh blood had a high signal intensity on T2-weighted images. A marked overlap of the relaxation parameters between intact kidney parenchyma and diffuse intrarenal hemorrhage was observed. Detection of dispersed intrarenal blood using spin echo MR imaging may be difficult.

Magnetic resonance imaging in the diagnosis of acute renal allograft rejection and its differentiation from acute tubular necrosis. Experimental study in the dog.

This study was designed to evaluate the potential utility of magnetic resonance imaging (MRI) for the diagnosis of acute renal allograft rejection and its differentiation from acute tubular necrosis (ATN). Eighteen canines were used. Five animals served as controls. ATN was induced in six animals by cross-clamping of the left renal artery for 90 minutes. In order to study acute renal allograft rejection, seven animals were subjected to exchange allograft transplantation of the left kidney. MRI was performed with a 0.35T superconductive magnet. A double spin-echo technique was used with varying TR and TE parameters. The spin echo images were analyzed for morphology, signal intensity, T1 and T2 relaxation times, and spin density. The most useful MRI criteria for the diagnosis of ATN and acute rejection were found to be the renal size, the intensity difference between cortex and medulla (corticomedullary contrast), and the T1 relaxation time of the cortex. Normal kidneys showed maximal corticomedullary contrast (19% +/-2) on images obtained with TR = 0.5 sec and TE = 28 msec. Cortical T1 relaxation time was 551 msec + /-73. In the ATN group, the kidneys were slightly swollen (P = ns) and the corticomedullary contrast (11% + /-3) was reduced by 42% (P less than .01). T1 of the cortex (689 + /-142) was increased by 25% (P less than .10). In acute rejection, significant renal enlargement was noted (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of lactate in acutely ischemic rat kidneys using magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Quantification of lactate in the kidney by 1H magnetic resonance spectroscopy (MRS) is a difficult task because of the presence of large amounts of peri-renal fat. When an editing scheme is used to detect lactate that filters out all resonances except lactate, there is no suitable metabolite to serve as an internal standard. In this study, the authors evaluate the potential of MRS to measure the absolute lactate concentration in rat kidneys during acute ischemia using MRS. MATERIALS AND METHODS: The authors propose a method based on a double resonance lactate editing scheme used in combination with the fully relaxed water peak as an internal standard. Experiments were performed on the left kidney rendered ischemic in eight rats. RESULTS: Renal lactate concentrations measured by MRS were compared with values derived from chemical analysis. The mean (+/- standard deviation) renal lactate concentrations measured by MRS and determined chemically were 12 +/- 1.2 umol/g, and 12.94 +/- 1.07 umol/g wet weight, respectively. The coefficient of variation for paired observations was 2.96%, indicating excellent agreement between the two methods used for measuring lactate. DISCUSSION: The study results demonstrate that it is possible to assess the lactate concentration in a rat model of ischemic kidney with MRS and suggest that the total lactate pool is detectable by this method under these experimental conditions.

Lactate accumulation in ischemic- and anoxic-isolated rat hearts assessed by H-1 spectroscopy.

Proton magnetic resonance (MR) spectroscopy with homonuclear editing was used to assess lactate accumulation in ischemic and anoxic hearts perfused according to the Langendorff method. An increase in the lactate signal was observed after 5 minutes of ischemia and after 10 to 20 minutes of anoxia. This study demonstrates that proton MR spectroscopy can be used to monitor the time course of MR-visible lactate levels in ischemic and anoxic isolated rat hearts.

Magnetic resonance imaging and spectroscopy of the periarticular inflammatory soft-tissue changes in experimental arthritis of the rat.

Arthritis was induced in rats by intradermal injection of Freund's complete adjuvant. MRI was performed with a resistive imager operating at 0.35 T. A spin echo (SE) technique with TR = 0.5 and 2.0 seconds, TE = 28 and 56 msec was used. Transaxial images of hindpaws and knees were obtained at different times after injection of adjuvant. In vitro proton spectroscopy of normal and arthritic hindpaws was also performed. Histologic confirmation was obtained in each case. Inflammatory soft-tissue lesions were seen as focal areas of high intensity on spin echo images obtained with TR = 2.0 seconds and TE = 56 msec and were characterized by long T1 and T2 relaxation times and high spin density. In comparison with both conventional radiography and physical examination, early soft-tissue changes were detected more frequently by MRI. This study suggests that MRI is likely to be of value for the early diagnosis of arthritis.

Changes in proton relaxation times of the rat spleen during adjuvant-induced immunologic reaction.

Possible changes in magnetic resonance (MR) relaxation times resulting from an immune reaction were evaluated in the rat spleen by means of in vitro proton spectroscopy and an established model of immune disease. Heat-killed Mycobacterium butyricum in Freund's adjuvant was injected intradermally into the tail of 28 rats. Ten normal rats served as controls. At different times following the injection of adjuvant (day 7, day 10, day 12, day 14, or day 22), the spleens were removed and weighed, and proton T1 and T2 relaxation times were measured with a 0.25-T spectrometer (10.7 MHz). Water content was also determined. Specimens of each spleen were histologically examined; this included Prussian-blue staining for detection of hemosiderin. In 22 of the 28 adjuvant-injected rats, spleen T1 values increased significantly, from a mean value of 451 msec +/- 23 S.D. (control rats) to a maximum mean value of 571 +/- 15 S.D., which occurred on day 12; this T1 increase paralleled an increase in weight and water content and a histologic appearance of granulomatous inflammation. In these rats, T2 changes were not significant. In the other six adjuvant-injected rats, spleen T2 relaxation time significantly decreased from a mean value of 42 msec +/- 5 S.D. to a mean value of 32 msec +/- 1 S.D. Histologic evaluation indicated that the origin of this T2 decrease was probably the presence of hemosiderin in the spleens of only these six rats. Mean T1 of these spleens decreased slightly, but not significantly.

Detection of experimental hepatic tumors using long circulating superparamagnetic particles.

RATIONALE AND OBJECTIVES: To evaluate the potential of an iron oxide-based MR contrast agent for the detection and delineation of experimental liver tumors during the early vascular phase of the compound. METHODS: Superparamagnetic blood pool agent (SBPA) was administered intravenously to rabbits bearing VX2 tumors. Images were acquired before the injection, immediately after, and 1 or 3 weeks later. The variations of signal intensity were measured in the tumors and in several tissues for various T1-weighted spin-echo, T2-weighted fast spin-echo, and T2-weighted gradient-recalled-echo sequences. RESULTS: Fourteen and 12 of the 16 tumors were detected immediately after SBPA injection using, respectively, the T2-weighted fast spin-echo and T2-weighted gradient-recalled-echo sequences. A significant decrease in signal intensity was observed in well-perfused organs, and blood signal was abolished even at the lowest injected dose and using a T1-weighted sequence. In the late phase, the loss in signal intensity of the liver was even more pronounced. CONCLUSION: The dominant T2 effect of SBPA induces an increase in the tumor-to-liver and tumor-to-blood contrast during the vascular phase, improving the detection of the tumors and allowing the distinction between small lesions and vessels through plane. This effect on the liver signal persists for several days because of the incorporation of SBPA in the reticuloendothelial system.

Continuous 5-day infusion of ifosfamide with mesna in inoperable pancreatic cancer patients: a phase II study.

Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.

Human intramuscular temperature and heat flow transients at rest.

A general model for heat exchange, comprising the major models in the literature, was developed. Temperature changes as a function of space and time were determined in six resting humans (age 32.7 +/- 4.5 yr) during temperature transients by magnetic resonance imaging (MRI), so that the exact solution of the model was obtained. These results allowed application of the model, e.g., the analysis of transient muscle heat flow changes, which could not be assessed by previous steady-state analyses. A microthermocouple was inserted in muscle vastus lateralis 2-3 cm below the skin surface. The measured temperature was used for calibrating the pixel intensity of a temporal series of transaxial magnetic resonance images obtained with a spin echo sequence around the microthermocouple position. After muscle temperature was increased by immersion in a controlled water bath, MRI acquisition was performed while muscle temperature was decreasing. Temperature maps relative to space and time inside a homogeneous region of interest were reconstructed by neural networks, showing specific temperature patterns. Subsequently calculated heat flows (with negative sign) appeared to increase linearly as temperature decreased, until a maximum was attained at a critical temperature, below which dramatic consistent heat flow changes were found. In conclusion, MRI is indeed a powerful technique, useful to study the determinants of muscle temperature and heat flow changes in space and time.

Energy metabolism and interstitial fluid displacement in human gastrocnemius during short ischemic cycles.

Energy metabolism and interstitial fluid displacement were studied in the human gastrocnemius during three subsequent 5-min ischemia-reperfusion periods [ischemic preconditioning (IP)]. The muscle energy balance was assessed by combining near-infrared spectroscopy (NIRS) and 31P-nuclear magnetic resonance spectroscopy (31P-NMRS). The interstitial fluid displacement was determined by combining NIRS and 23Na-NMRS. No changes in total energy consumption or in the fractional contribution of the underlying energy sources (aerobic glycolysis, anaerobic glycolysis, and Lohmann reaction) were observed in the muscle during the tested IP protocol. Oxygen consumption in the muscle region of interest, as estimated by NIRS, was approximately 8 micromol . 100 g-1 . min-1 and did not change during IP. Phosphocreatine and ATP concentrations did not change over the whole experimental period. A slight but significant (P < 0.05) increase in intracellular pH was observed. Compared with the control, a 10% greater interstitial fluid content per muscle unit volume was observed at the end of the IP protocol. It is concluded that, at variance with cardiac muscle, repeated 5-min ischemia-reperfusion cycles do not induce metabolic changes in human gastrocnemius but alter the interstitial fluid readjustment. The techniques developed in the present study may be useful in identifying protocols suitable for skeletal muscle preconditioning and to explain the functional basis of this procedure.

The levelling effect of solvational imbalances in the reactions of oximate alpha-nucleophiles with electrophilic phosphorus centers. Relevance to detoxification of organophosphorus esters.

A study of the reactions of oximate alpha-nucleophiles with diisopropylphosphorofluoridate (DFP) and two model phosphonates, has revealed either a levelling-off in reactivity or a bell-shaped behaviour in accordance with a critical decoupling of desolvation and bond formation (solvational imbalances); the relevance of these results to detoxification is emphasized.

Twinkling artifact on intracerebral color Doppler sonography.

Transcranial Doppler sonography shows potential as a noninvasive technique for long-term follow-up of treated intracranial saccular aneurysms. This technical note describes a color Doppler artifact related to microcoil architecture that might represent a potential pitfall in transcranial Doppler sonographic evaluation of aneurysmal cavity thrombosis, since it may be wrongly interpreted as residual flow or aneurysmal cavity recanalization.

Dual behavior of 4-aza-6-nitrobenzofuroxan. A powerful electrophile in hydration and sigma-complex formation and a potential dienophile or heterodiene in diels-alder type reactions

In investigating the reactivities of aza analogues of super-electrophile 4,6-dinitrobenzofuroxan (DNBF, 1), we have found that the nitro-substituted pyridofuroxan 2 gives a remarkably stable hydrate 3 in aqueous solution (as evidenced by the requirement of ca. 50% H(2)SO(4) (H(0) approximately -3) for complete recovery of 2). The equilibrium constant K(H)()2(O) for hydration of 2 is estimated to be >/= 100, being comparable only with the K(H)()2(O) values reported for hydration of highly activated neutral polyazaaromatics such as 2- and 6-hydroxypteridines or 7-azapteridine. Interestingly, the NH group of 3 undergoes ionization at rather low pH (p = 5.79), affording an anionic hydroxy sigma-adduct 4 which is thermodynamically 10(8) times more stable than the related sigma-adduct of pteridine. The experimental evidence is that 4 is slightly more stable than the hydroxy sigma-adduct of DNBF, indicating not only that 2 ranks among the most electrophilic heteroaromatics known to date but also than an aza group may in fact be as efficient as a nitro group in promoting sigma-complex formation. 2 is also found to be a versatile Diels-Alder reagent, as a result of the low aromatic character of its six-membered ring. Upon treatment of 2 with cyclopentadiene and 2,3-dimethylbutadiene, various reactivity patterns have been observed. These led to different cycloadducts arising from normal as well as inverse electron-demand condensations involving the pyridine ring as the dienophile or the heterodiene contributor. Altogether, the results reveal major differences between the reactivity of 2 and that of DNBF, with in particular a remarkable tendency of the pyridofuroxan adducts to undergo covalent hydration, resulting in the formation of stable carbinolamines. Also noteworthy is the characterization of a diadduct which results from a Diels-Alder trapping of the o-dinitroso intermediate involved in the exchange of the 1-oxide and 3-oxide tautomers of 2.

MRI of a retained sponge in a dog.

Retained sponges after laparotomy may cause a broad spectrum of clinical symptoms and present a difficult diagnostic problem. We report a case of retained surgical sponge in a dog to illustrate the MRI findings of this infrequent but important cause of postoperative complications.

Enhancement of computed tomography liver contrast using iomeprol-containing liposomes and detection of small liver tumors in rats.

RATIONALE AND OBJECTIVES: We evaluated iomeprol-containing liposomes (Lipiom), a new contrast medium for computed tomography (CT) liver scanning, in an animal model of chemically induced hepatocellular carcinomas and other liver tumors in rats. METHODS: Liver tumors were induced by administration of carcinogens to rats, either 0.55% (w/w) 1'-hydroxysafrole in the diet or induction by 3'-methyl-4-diethylaminoazobenzene followed by promotion with carbon tetrachloride. CT scanning was performed 1-3 hr after intravenous injection of iomeprol-containing liposomes. RESULTS: After injection of iomeprol-containing liposomes at a dose of 70 mg of liposome-entrapped iodine per kilogram of body weight, the normal liver parenchyma showed a contrast enhancement, in Hounsfield units, of more than 60% over the control value before bolus. Liver tumors with no or few Kupffer cells were not enhanced and appeared as dark areas within the normal parenchyma. Tumors and pretumoral lesions devoid of Kupffer cells, as small as 3 mm in diameter, could be distinguished using this non-invasive method. CONCLUSION: CT liver scanning after injection of iomeprol-containing liposomes appears to be promising method for detecting liver tumors and focal liver lesions.