Motion artifact reduction with fast spin-echo imaging

The influence of signal averaging (n), repetition time (TR), and echo delay (TE) on systematic noise (cardiac, vascular, respiratory, and peristaltic ghost artifacts) and statistical noise (thermal effects) was determined in eight healthy volunteers and 57 patients. Systematic noise was the dominant factor degrading abdominal magnetic resonance (MR) images. Signal averaging was the primary determinant of both statistical and systematic image noise, fitting a power function (n)b with b = 0.44 and -0.42, respectively, close to the expected b = -0.5 power function. All types of ghosting showed the same sensitivity to signal averaging. Normalized systematic noise increased slightly with TR (b = 0.16) and increased markedly with TE (b = 0.40). These data indicate that the short TR, short TE technique is a powerful method for reducing motion artifacts on breathhold images and can be combined with signal averaging to further suppress artifacts, improve signal-to-noise ratio, and maximize anatomic resolution.     

Skin lesions from hypersensitivity to cold during chronic myelomonocytic leukaemia

A patient with chilblain lupus and chronic myelomonocytic leukaemia (CMML) is reported. The possible mechanisms of this association which appears specific to CMML are briefly discussed.     

Gastrointestinal tract: dynamic MR studies with echo-planar imaging

Gastrointestinal (GI) tract motility was depicted in four human volunteers with the high-speed echo-planar imaging technique: modulus blipped echo-planar single-pulse technique (MBEST). Data acquisition times of 64 and 128 msec obviate image degradation due to motion without the need for gut paralysis and allow imaging of the GI tract in real time. Peristaltic patterns of the gastric antrum and proximal small intestine were depicted for fasting and fed subjects and subjects in whom peristalsis had been pharmacologically stimulated. The potential for quantitative measurements of GI tract motion with this new technique was demonstrated.     

Development of sulfasalazine resistance in human T cells induces expression of the multidrug resistance transporter ABCG2 (BCRP) and augmented production of TNFalpha

OBJECTIVE: To determine whether overexpression of cell membrane associated drug efflux pumps belonging to the family of ATP binding cassette (ABC) proteins contributes to a diminished efficacy of sulfasalazine (SSZ) after prolonged cellular exposure to this disease modifying antirheumatic drug (DMARD). METHODS: A model system of human T cells (CEM) was used to expose cells in vitro to increasing concentrations of SSZ for a period of six months. Cells were then characterised for the expression of drug efflux pumps: P-glycoprotein (Pgp, ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). RESULTS: Prolonged exposure of CEM cells to SSZ provoked resistance to SSZ as manifested by a 6.4-fold diminished antiproliferative effect of SSZ compared with parental CEM cells. CEM cells resistant to SSZ (CEM/SSZ) showed a marked induction of ABCG2/BCRP, Pgp expression was not detectable, while MRP1 expression was even down regulated. A functional role of ABCG2 in SSZ resistance was demonstrated by 60% reversal of SSZ resistance by the ABCG2 blocker Ko143. Release of the proinflammatory cytokine tumour necrosis factor alpha (TNFalpha) was threefold higher in CEM/SSZ cells than in CEM cells. Moreover, twofold higher concentrations of SSZ were required to inhibit TNFalpha release from CEM/SSZ cells compared with CEM cells. CONCLUSION: Collectively, ABCG2 induction, augmented TNFalpha release, and less efficient inhibition of TNFalpha production by SSZ may contribute to diminished efficacy after prolonged exposure to SSZ. These results warrant further clinical studies to verify whether drug efflux pumps, originally identified for their roles in cytostatic drug resistance, can also be induced by SSZ or other DMARDs.     

The neurologic sequelae of cardiopulmonary bypass-induced cerebral hyperthermia and cerebroprotective strategies

Cerebral hyperthermia during the rewarming phase of cardiopulmonary bypass (CPB) is associated with adverse outcomes. Cerebral hyperthermia can exacerbate a preexisting injury prior to rewarming, and may be damaging in itself. Temperature and cerebral metabolic rate (CMRO2) play a vital role in cerebral autoregulation. Therefore, hyperthermia can have a strong impact on cerebral oxygen transfer, and neurologic outcome. Glutamate levels can increase during cerebral hyperthermia, leading to eventual cell death. Rapid rewarming decreases jugular venous hemoglobin saturation, creating a mismatch between cerebral oxygen consumption and delivery. With these ill effects in mind, cerebral protection during CPB is imperative. Special attention should be given during rewarming to prevent these harmful outcomes. Pharmacologic agents such as sodium nitroprusside can be used to assist the rewarming process. Temperature management is the key component during the rewarming phase of CPB in the prevention of cerebral hyperthermia.     

Antifolate resistance associated with loss of MRP1 expression and function in Chinese hamster ovary cells with markedly impaired export of folate and cholate

Export of folates from a Chinese hamster ovary PyrR100 cell line is markedly impaired, resulting in expansion of cellular folate pools and high-level antifolate resistance. We now report that MRP1 expression is absent in PyrR100 cells along with a marked decrease in MRP5 expression with 3-fold cross-resistance to thiopurines. PyrR100 and wild-type cells had comparable low levels of MRP2 expression; both lacked the breast cancer resistance protein. PyrR100 cells showed a 4-fold decrease in cholate (an MRP substrate) efflux with a 6-fold increase in cellular cholate accumulation compared with wild-type cells. Prostaglandin A1 increased cholate accumulation in wild-type cells to levels comparable with PyrR100 cells. Calcein (an MRP1 substrate) fluorescence increased 5-fold in PyrR100 cells; probenecid increased the intracellular calcein level in wild-type cells to that of PyrR100 cells. Consistent with the loss of MRP1 expression, PyrR100 cells showed modest collateral sensitivity to cholate, etoposide, doxorubicin, and vincristine. Transfection of MRP5 into PyrR100 cells did not alter sensitivity to pyrimethamine or MTX but restored sensitivity to mercaptopurines, indicating that decreased MRP5 expression did not play a role in antifolate resistance. Hence, although MRP-mediated anticancer drug resistance has been associated with gain of function (i.e., overexpression), this is the first report that loss of MRP1 efflux function can expand intracellular folate pools to result in acquired antifolate resistance. The data also suggest that MRP1, and possibly other MRPs that transport folates, can play a role in the maintenance of cellular folate homeostasis.     

Anti-inflammatory,antipyretic and antinociceptive activities of Tabernaemontana pandacaqui Poir

Studies on carrageenin-induced rat paw edema, yeast-induced hyperthermia in rat and writhing response induced by acetic acid in mice showed that the alcoholic extract of stems of Tabernaemontana pandacaqui (T. pandacaqui) has significant anti-inflammatory, antipyretic and antinociceptive activities. These activities are due to alkaloidal components since they were also observed when the crude alkaloidal (CA) fraction separated from alcoholic extract was tested in the same models.