DWI prediction of symptomatic hemorrhagic transformation in acute MCA infarct

PURPOSE: Symptomatic hemorrhagic transformation is a severe complication of acute ischemic stroke which occurs at a higher frequency after thrombolysis. The present study was designed to analyze whether early DWI can be used for predicting the risk of hemorrhagic transformation with clinical worsening in MCA stroke patients. MATERIALS AND METHODS: Of 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MR angiography performed within 14 hours after onset (mean 6.5 +/- 3.5 hours, median 5.2 hours), 4 developed hemorrhagic transformation with clinical worsening, while 24 did not. For the 2 groups, we compared admission NIHSS score, site of arterial occlusion, volume of DWI abnormalities, and several apparent diffusion coefficient (ADC) measurements: ADC(infarct) (mean ADC value of the whole infarct), ADC(core) (peak ADC decrease as calculated in a 57 mm(2) circular ROI, manually centered on the ischemic area with the lowest ADC value on the ADC maps), ADC(superficial) and ADC(deep). Discriminant function analysis was used to determine the most accurate predictors of symptomatic hemorrhagic transformation. RESULTS: The best predictor was the ADC(core) (F=5.34, p=2.9%, cut-off value=300 x 10(-6) mm(2)/s). This monovariate model allowed to correctly classify all 4 patients (ADC(core) 300 x 10(-6) mm(2)/s) with subsequent symptomatic hemorrhage, and 17 of the 24 patients without symptomatic hemmorrhage (ADC(core)>300 x 10(-6) mm(2)/s) (100% sensitivity, 71% specificity). CONCLUSION: Although preliminary, these results suggest that a simple measurement of minimum ADC values within an acute MCA stroke could be useful in targeting those patients with a high risk of severe hemorrhagic transformation.     

Isolation of a Novel Gene Showing Reduced Expression in Metastatic Colorectal Carcinoma Cell Lines and Carcinomas

To investigate genes involved in mctastatic stages of cancer, we analyzed expression of mRN As in three cell lines derived from murine colon adenocarcinoma 26 by means of a differential display method. Each of these lines exhibits distinct metastatic characteristics. Among many bands representing different expression patterns in the display, we confirmed by northern analysis that a gene corresponding to one amplified fragment, termed grm2 (gene related to metastasis 2), was expressed more abundantly in NL4, the derivative with the lowest metastatic potential, than in cell lines NL17, an experimentally metastatic derivative, and in NL22, a spontaneously metastatic derivative. Using thegrm.2 fragment as a probe, we isolated murine cDNA clones and subsequently human cDNA clones corresponding to the GRM2 gene. The human and mouse homologues both encode proteins of 600 amino-acid residues, which show weak homologies to proteins belonging to the myosin family. When we examined the expression levels of this novel gene in human colon cancers and in corresponding metastatic foci, we found that in more than half of these tissues, expression was significantly reduced in association with malignant potential. Our resultsimply that in humans the GRM2 gene product may regulate the metastatic phenotype of some colorectal cancers.     

Acupuncture in the prophylactic treatment of migraine without aura: a comparison with flunarizine

OBJECTIVES: In a randomized controlled trial extending over 6 months, we evaluated the effectiveness of acupuncture versus flunarizine in the prophylactic treatment of migraine without aura. METHODS: One hundred sixty women with migraines were randomly assigned to acupuncture treatment (group A, n = 80) or to an oral therapy with flunarizine (group F, n = 80). In group A, acupuncture was carried out in weekly sessions for the first 2 months and then once a month for the next 4 months. The same acupoints were used at each treatment: LR3 Taichong, SP6 Sanyinjiao, ST36 Zusanli, CV12 Zhongwan, LI4 Hegu, PC6 Neiguan, GB20 Fengchi, GB14 Yangbai, EX-HN5 Taiyang, GV20 Baihui. In group F, 10 mg flunarizine were given daily for the first 2 months and then for 20 days per month for the next 4 months. RESULTS: The frequency of attacks and use of symptomatic drugs significantly decreased during treatment in both groups. The number of attacks after 2 and 4 months of therapy was significantly lower in group A than in group F, and analgesic consumption was significantly lower in group A at 2 months of treatment. At 6 months no such differences existed between the two treatment groups. Pain intensity was significantly reduced only by acupuncture treatment. Side effects were significantly less frequent in group A. CONCLUSIONS: Acupuncture proved to be adequate for migraine prophylaxis. Relative to flunarizine, acupuncture treatment exhibited greater effectiveness in the first months of therapy and superior tolerability.     

Probucol decreases mevalonate pyrophosphate decarboxylase in the rat liver

It is known that cholesterol biosynthesis in the liver is inhibited by probucol. This inhibition by probucol is caused at least in part by a decrease in 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. In this study, we examined serum cholesterol and the change in the activity or protein level of mevalonate pyrophosphate decarboxylase (MPD), which is involved in cholesterol biosynthesis, in the livers of rats fed probucol. The results indicated that serum cholesterol, MPD activity and MPD protein were decreased by 70, 50 and 60% by probucol, respectively, as compared with those in rats fed normal chow. These data show for the first time that probucol decreases the level of an enzyme involved in cholesterol biosynthesis other than HMG-CoA reductase.     

Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein,is expressed in intestinal epithelium

The Na+/H+ exchangers (NHEs) comprise a family of membrane proteins that catalyze the electroneutral exchange of Na+ and H+. Calcineurin homologous protein (CHP) acts as a crucial cofactor for NHE activity through direct interaction with the carboxyl-terminal tail region of NHEs. We have cloned a new rat CHP isoform (rCHP2) and characterized the binding property to NHEs and the tissue distribution. rCHP2 binds to the juxtamembrane region of plasma membrane-type NHE isoforms (NHE1-5) in vivo and in vitro as well as rCHP1 (original rat CHP). Interestingly, CHP2 is predominantly expressed in the small and large intestine although rCHP1 shows relatively ubiquitous expression at both the mRNA and protein levels. In situ hybridization experiments demonstrated the abundant expression of CHP2 in the epithelial cell layer of villi of the small intestine in contrast with the expression of CHP1 in both the epithelial layer and connective tissues. These results suggest that CHP2 functions in the absorptive epithelium for the intestine with NHE(s).     

Subcellular distribution of mouse mevalonate pyrophosphate decarboxylase

Mevalonate pyrophosphate decarboxylase (MPD) is considered to be a cytosolic protein. Recently, other groups reported that MPD is mostly located in the peroxisomes. In this study, we examined whether the expression of MPD in mice depends on the proliferation of peroxisomes, and whether MPD is predominantly located in the peroxisomes or the cytosol of mice. No increase in the protein level of MPD was observed in the crude extract of the livers of mice administered with peroxisome proliferative drugs. The result suggests that the expression of MPD is independent of the proliferation of peroxisomes, and may be maintained via a specific regulatory mechanism, different from the regulation of the expression of peroxisome proliferator-activated receptor alpha. When the subcellular distribution of MPD in mouse melanoma (B16F10) cells was examined by cell fractionation, MPD was detected in the cytosol of B16F10 cells, but not in the peroxisomes. In permeabilized B16F10 cells treated with digitonin, which lack cytosolic enzymes, 80% and 20% of MPD, 75% and 25% of lactate dehydrogenase, or 2% and 98% of catalase, existed in the medium and in the cell, respectively. From these results, it indicated that MPD was predominantly located in the cytosol and did not exist in the peroxisomes of B16F10 cells.     

Socioeconomic Disparities Are Negatively Associated with Pediatric Emergency Department Aftercare Compliance

OBJECTIVES: This study sought to identify demographic, socioeconomic, and clinical predictors of aftercare noncompliance by pediatric emergency department (ED) patients. METHODS: The authors conducted a prospective, observational study of pediatric patients presenting to a university teaching hospital ED from July 1, 2002, through August 31, 2002. Demographic and clinical information was obtained from guardians during the ED visit. Guardians were contacted after discharge to determine compliance with ED aftercare instructions. Subjects were excluded if they were admitted or if guardians were unavailable or unwilling to consent. Data were analyzed using multivariable logistic regression to identify predictors of noncompliance from a list of predetermined variables. RESULTS: Of the 409 patients enrolled in the study, 111 were prescribed medications and 364 were given specific follow-up instructions. Subtypes of the variable "insurance status" were significantly associated with medication noncompliance in multivariable regression analysis. "Insurance status" and "low-acuity discharge diagnoses" were significantly associated with follow-up noncompliance. CONCLUSIONS: Disparity in health insurance has been shown to be a predictor of poor aftercare compliance for pediatric ED patients within the patient population.