Leptomeningeal collateral status predicts outcome after middle cerebral artery occlusion.

OBJECTIVES: Perfusion through leptomeningeal collateral vessels is a likely pivotal factor in the outcome of stroke patients. We aimed to investigate the effect of collateral status on outcome in a cohort of unselected, consecutive stroke patients with middle cerebral artery occlusion undergoing reperfusion therapy. MATERIALS AND METHODS: This retrospectively planned analysis was passed on prospectively collected data from 187 consecutive patients with middle cerebral artery occlusion admitted within 4.5 hours to one center and treated with intravenous thrombolysis alone (N = 126), mechanical thrombectomy alone (N = 5), or both (N = 56) from May 2009 to April 2014. Non-contrast CT (NCCT) and computed tomography angiography (CTA) were provided on admission and NCCT repeated at 24 hours. Collateral status was assessed based on the initial CTA. Hemorrhagic transformation was evaluated on the 24-hour NCCT and according to European Cooperative Acute Stroke Study (ECASS) criteria. Modified Rankin Scale score was assessed at 90 days, and mortality at 1 year. RESULTS: At 90 days, median (IQR) modified Rankin Scale score in patients with poor collateral status was 4 (3-6) compared to 2 (1-4) in patients with good collateral status (P < .0001). Patients with poor collateral status were less likely to achieve a good 90-day outcome (modified Rankin Scale score 0-2) (Adjusted odds ratio 0.27, 95% CI: 0.09-0.86). During the first year, 40.9% of patients with poor collateral status died vs 18.2% of the remaining population (P = .001). CONCLUSIONS: Leptomeningeal collateral status predicts functional outcome, mortality, and hemorrhagic transformation following middle cerebral artery occlusion.

Prevalence of negative CT scans in a level one trauma center.

PURPOSE: The rise of computed tomography (CT) use in trauma has become the subject of concern given the harms of CT including radiation, cost, over diagnosis and identification of incidental lesions. We developed a novel metric, the Negative CT Score, (∑CT-) which quantifies how often CT imaging identifies important injuries. Our objective was to describe the pattern of CT utilization in trauma at an urban academic level one trauma center using this novel metric. METHODS: This was a retrospective study of intermediate level trauma patients who received CT imaging over a 1-year study period at an urban level one trauma center. We applied the Negative CT Score, (∑CT-) to quantify the results of CT imaging. ∑CT- is computed by subtracting the number of non-extremity body regions (maximum four: head, neck, chest, abdomen) with an important positive CT finding (defined by a priori criteria) from the total number of non-extremity body regions scanned. RESULTS: Of the 552 cases reviewed during the study period, 410 (74.3%) were male and the mean age was 40.3 years [SD ± 21.2]. Four hundred eighty-six patients (88.0%) suffered blunt trauma; 66 (12.0%) suffered penetrating trauma. The average injury severity score for admitted patients was seven. Four hundred ninety-five cases had at least one CT performed. The average number of regions per patient that received CT imaging was 2.36 (SD ± 1.3), and the average ∑CT- was 2.10 (SD ± 1.2). Three hundred and sixty-seven (74.3%) patients had no important findings on CT imaging. CONCLUSIONS: In a consecutive series of 552 intermediate trauma patients at our urban trauma center, 2.36 body regions were scanned per patient; of these, 2.10 regions revealed no important CT findings. We hope that these results and the Negative CT Score can be used to identify trends, variations in practice, and outliers within and across departments so that CT utilization can be optimized.

The effect of UHT-processed dairy milk on cardio-metabolic risk factors.

BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) remains a major cause of death worldwide. Whereas dairy generally is associated with a neutral or a beneficial CVD effect, the consumption of ultra-high temperature (UHT)-treated milk has been reported to increase levels of low-density lipoprotein cholesterol (LDL-C) in an uncontrolled study. Our aim was to examine whether semi-skimmed UHT dairy milk increases the risk of CVD development compared with pasteurized (PAST) dairy milk in overweight healthy adults. SUBJECTS/METHODS: Nineteen healthy men and women participated in a randomized, controlled, crossover study. The effect of intake of 1.5 l of UHT dairy milk or PAST milk, similar in nutritional content, was examined as a supplement to the participant's habitual diet for 21 days in each intervention period. Intake of other dairy products was not allowed during the intervention period. Clinical evaluation and blood samples took place preintervention and postintervention. RESULTS: There was no significant effect by type of milk on LDL-C (P=0.29). No effects of type of milk were observed in other blood lipid levels, such as total cholesterol, high-density lipoprotein cholesterol or triglycerides. No effects of type of milk were found for blood pressure, insulin, glucose concentration and insulin resistance (homeostasis model assessment of insulin resistance) or body weight. CONCLUSIONS: This study does not support the hypothesis that UHT processing of milk increases the risk of CVD.

Stroke severity and incidence of acute large vessel occlusions in patients with hyper-acute cerebral ischemia: results from a prospective cohort study based on CT-angiography (CTA).

BACKGROUND: The frequency of acute large vessel occlusions in relation to clinical severity has not yet been established in a comprehensive, consecutive and unselected cohort of patients with hyper-acute cerebral ischemia. AIM: The aim of this study was to establish the frequency of acute large vessel occlusions and describe the relations to the National Institutes of Health Stroke Scale (NIHSS), lesion site and time from symptom onset in unselected consecutive patients with hyper-acute cerebral ischemia. METHODS: A prospective single hospital registry was based on consecutive unselected patients admitted from July 2009 to December 2011 with symptoms of acute cerebral ischemia within 4.5 h from symptom onset. ICA, M1, M2, ACA, PCA, BA and VA were assed for occlusions. Best NIHSS-cut-off values were calculated based on sensitivity and specificity for detecting any, anterior and posterior occlusions and the effect of time after symptom onset was assessed. RESULTS: Six hundred thirty-seven patients, with admission NIHSS: 1-42, were included; 183 patients presented with acute vessel occlusions (28.7%) in 15 different combinations of occlusions. The best NIHSS-cut-off for detecting any occlusion was 6. NIHSS is highly depending on lesion site, highest values being observed in relation to combined and M1 occlusions. CONCLUSION: Acute vessel occlusions are frequent in unselected patients. Occlusions occurred in all NIHSS score values but a NIHSS cut-off value of 6 most optimally predicted acute vessel occlusion, even though accuracy was low.

Emergency department consultations for patients with neurological emergencies.

BACKGROUND: The spectrum of neurological emergencies that front-line physicians encounter is diverse. Appropriate assessment and neurological consultation is essential to good patient outcomes because many of these conditions depend on the rapid initiation of proper therapy. METHODS: In this retrospective study, we reviewed patients for whom the emergency physician elected to consult a neurologist to categorize the types of complaints, resources utilized, patient disposition and final diagnoses. RESULTS: Of the 500 patients analyzed in our study, the most common chief complaints were focal weakness (22%), headache (18.2%), dizziness or vertigo (16%), and seizure (14.2%). The most common reasons for neurological consultation were specific symptom (70.6%), concern for a specific diagnosis (17.4%), specific radiologic finding (9.2%), and ambiguity in the diagnosis (2.8%). Overall stroke accounted for 18.6% of the cases in our study. Non-contrast brain computed tomography was the most common imaging study (72.2%), and 37.0% of patients received advanced neuroimaging. The presentation of patients varied as 47% presented without having been seen by another healthcare professional, 24% were referred to the emergency department (ED) following by some other outpatient provider for evaluation, and 29% were transferred from another ED. CONCLUSIONS: Patients with neurological emergencies are common and consume a disproportionate amount of resources in the ED. Emergency physician training must target the modern evaluation of patients with a large variety of neurological emergencies and place special emphasis on the evaluation of patients with weakness, seizures, headache, and dizziness.

Fluctuating asymmetry in mice and rats: evaluation of the method.

Fluctuating asymmetry, which reflects small, random deviations from symmetry in otherwise bilaterally symmetrical characters, may be used as an indicator of developmental instability in humans and farm animals, and it may also be applicable as a stress indicator. We intended to find a method to allow the use of fluctuating asymmetry as a stress indicator in laboratory animals. That method had to be reproducible and reliable. Furthermore, its applicability in laboratory animals would be improved if it was possible to obtain measurements on the skin surface that correlated with results obtained by measuring the skeleton directly. Seven traits in mice and five traits in rats were evaluated for their applicability for measuring fluctuating asymmetry in mice and rats. Two out of the seven traits, i.e. the width of the joint between the third metatarsal bone and the digital bone on the hind paw, and the length of the incisor tooth at the top, were found to be reliable and reproducible for detecting fluctuating asymmetry in mice as well as in rats. Three out of the seven traits, i.e. the width of the carpal bones, the width of the joint between the tibia and the tarsal bones, and the length of the incisor tooth at the bottom, did express fluctuating asymmetry, but showed a poor day-to-day reproducibility. If the day-to-day reproducibility could be increased, these three traits might also be suitable for measuring fluctuating asymmetry in mice and rats. The last two traits, i.e. the length of ulna and the length of calcaneus plus metatarsal bone i.v., measured both on the skin surface and directly on the bone, did not express fluctuating asymmetry, and had a poor day-to-day reproducibility. These two traits are not suitable for measuring fluctuating asymmetry in mice and rats.

Comparison of assays for antibodies to Encephalitozoon cuniculi in rabbits.

Two indirect immunofluorescence (IIF) assays, two enzyme-linked immunosorbent assays (ELISAs) and the carbon immunoassay (CIA) for determination of antibodies to Encephalitozoon cuniculi were compared using 210 sera of rabbits, 135 of which originated from seven infected colonies, while 75 originated from four uninfected colonies. There was no evidence of a difference between the different assays with respect to the number of positive sera. There was a clear correlation between the quantitative response measured by IIF and CIA and the other assays, and between both IIF tests, while no such correlation was found in the quantitative response measured by ELISAs, which might be explained by the less quantitative nature of the ELISA. Therefore quantitative determination of antibodies to E. cuniculi should be performed by IIF and not by ELISA. The nosographic sensitivities N1 and specificities N2 of the assays were > or = 0.94 and > or = 0.97 respectively. Small differences in N1 and N2 between the assays, although not statistically significant, were responsible for differences in the calculated predictive values of a positive test and of a negative test. As expected, the magnitude of these differences depended on the fraction of positive sera sampled from a given colony. There was strong evidence of such a difference between the fraction of positive sera found in different colonies, but the sample size from some colonies was too small to allow any conclusion, whether this was due to differences in the prevalences of the infection in the colonies or something else. We conclude that any of the assays will be suitable for the routine health monitoring of laboratory rabbit colonies for E. cuniculi infection, as recommended by the Federation of European Laboratory Animal Science Associations.

Fibronectin type III-like sequences and a new domain type in prokaryotic depolymerases with insoluble substrates.

Fibronectin type III-like sequences are present in many proteins from higher eukaryotes and are involved in protein-protein interactions, heparin binding and cell adhesion. A nine-member family of bacterial sequences is shown to be significantly homologous to the type III-like sequences. All the sequences are contained in secreted depolymerases acting on complex, energy-rich insoluble substrates, in which they apparently do not participate in catalysis or substrate-binding, their exact function remaining unclear. Furthermore, a new family of sequences, present in some cellulases, is presented.

celA from Bacillus lautus PL236 encodes a novel cellulose-binding endo-beta-1,4-glucanase.

celA from the cellulolytic bacterium Bacillus lautus PL236 encodes EG-A, an endo-beta-1,4-glucanase. An open reading frame of 2,100 bp preceded by a ribosome-binding site encodes a protein with a molecular mass of 76,863 Da with a typical signal sequence. The NH2-terminal active domain of EG-A is not homologous to any reported cellulase or xylanase and may represent a new family of such enzymes. A 150-amino-acid COOH-terminal peptide is homologous to noncatalytic domains in several other cellulases (A. Meinke, N.R. Gilkes, D.G. Kilburn, R.C. Miller, Jr., and R.A.J. Warren, J. Bacteriol. 173:7126-7135, 1991). Upstream of celA, a partial open reading frame encodes a 145-amino-acid peptide which also belongs to the family mentioned. Zymogram analysis of extracts from Escherichia coli and supernatants of Bacillus subtilis and B. megaterium, including protease-deficient mutants thereof, which express celA, revealed two active proteins, EG-A-L and EG-A-S, with Mrs of 74,000 and 57,000, respectively. The proportion of EG-A-L to EG-A-S depends on the extracellular proteolytic activity of the host organism, indicating that EG-A-S arises from posttranslational proteolytic modification of EG-A-L. Since EG-A-S has an NH2 terminus corresponding to the predicted NH2-terminal sequence of EG-A, processing appears to take place between the catalytic and noncatalytic domains described. EG-A-L and EG-A-S were purified to homogeneity and shown to have almost identical characteristics with respect to activity against soluble substrates and pH and temperature dependency. EG-A-L binds strongly to cellulose, in contrast to EG-A-S, and has higher activity against insoluble substrates than the latter. We conclude that the COOH-terminal 17,000-Mr peptide of EG-A-L constitutes a cellulose-binding domain.

In vivo genetic engineering: homologous recombination as a tool for plasmid construction.

This paper describes a novel method for creating exact DNA fusions between any two points in a plasmid carried in Bacillus subtilis. It exploits the homologous in vivo recombination between directly repeated sequences that can be established by insertion of a synthetic oligodeoxyribonucleotide. The method was used to enhance the productivity in B. subtilis of a cloned alpha-amylase (Amy)-encoding gene originating from Bacillus stearothermophilus. Thus, an exact fusion between nucleotide sequences encoding the expression signals, including the signal peptide, of a Bacillus licheniformis Amy-encoding gene and the mature Amy of B. stearothermophilus, was created. The resulting hybrid translational product was processed correctly in B. subtilis during secretion, giving rise to an Amy identical to the mature Amy secreted by B. stearothermophilus.

Multiple endo-beta-1,4-glucanase-encoding genes from Bacillus lautus PL236 and characterization of the celB gene.

A Bacillus lautus strain was isolated from compost by its ability to degrade microcrystalline Avicel cellulose and acid-swollen cellulose. Three DNA fragments cloned in Escherichia coli encoded at least four endo-beta-1,4-glucanases (EG), of which at least two were contained on one DNA fragment. Another fragment, of 2.5 kb and carrying celB, was cloned in the shuttle-vector plasmid, pJKK3-1, and expressed in E. coli and Bacillus subtilis. The fragment was sequenced and shown to encode a 62-kDa protein, which was found as a 56-kDa mature and active EG in extracts of E. coli and in the supernatant of B. subtilis. The deduced amino acid (aa) sequence has a homology of 37% identical aa on a stretch of 295 aa to EG-E of Clostridium thermocellum. A low level of homology is detected with the Bacillus-type EG.