Comparison of dysprosium DTPA BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischemia in the rat

The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.     

Use of magnetic resonance imaging to define the anatomical location closest to all three cords of the infraclavicular brachial plexus

Infraclavicular techniques are often used to perform brachial plexus blocks. In our volunteer study we used magnetic resonance imaging to identify the brachial plexus and axillary vessels in a sagittal plane corresponding to the lateral sagittal infraclavicular block. In 20 volunteers, all cords were positioned within 2 cm from the artery approximately within 2/3 of a circle. We derived an injection site that was closest to all cords, cranio-posterior and adjacent to the axillary artery. We conclude that this knowledge may be useful for the performance of infraclavicular blocks aided by ultrasound. However, our proposals should be tested by clinical studies.     

Iron discoloration of acrylic resin exposed to chlorhexidine or tannic acid: a model study

A clinical model was introduced to study the ability of chlorhexidine, tannic acid, and iron to discolor dental plaque formed on acrylic resin surfaces. None of the agents caused discoloration when applied individually five times daily during a 5-day period. However, exposure of the dental plaque to either chlorhexidine or tannic acid before the iron applications produced marked staining. Possible mechanisms, among which denaturation appears to be significant, are discussed. The use of a strong oxidizing agent, peroxymonosulfate, completely bleached the established discolorations.     

Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamics in a placebo-controlled study involving stable patients with subarachnoid hemorrhage

OBJECTIVE: To compare the effects of a bolus infusion of hypertonic saline hydroxyethyl starch with the effects of normal saline (placebo) on intracranial pressure (ICP) and cerebral perfusion pressure in patients with spontaneous subarachnoid hemorrhage. DESIGN AND SETTING: Prospective, randomized, single-blinded, placebo-controlled study in a university hospital. PATIENTS: A total of 22 mechanically ventilated patients with spontaneous subarachnoid hemorrhage with stable ICP between 10 and 20 mm Hg. INTERVENTIONS: During the course of 30 mins, 2 mL/kg of either 7.2% saline in 6% hydroxyethyl starch 200/0.5 (HSS) or of normal saline was infused. The effects were observed for another 180 mins. MEASUREMENTS AND MAIN RESULTS: Mean change in ICP after intervention (DeltaICP) calculated from the average of all observations was -3.3 (sd 2.6) mm Hg in the HSS group vs. -0.3 (sd 1.3) mm Hg in the normal saline group. Mean difference between the groups (HSS - normal saline) was -3.0 mm Hg (95% confidence interval, -4.9 to -1.1; p = .004). Mean peak change after HSS was -5.6 (range, -0.8 to -12.2) mm Hg after 64 (range, 40 to 115) mins. Mean difference in cerebral perfusion pressure change between the groups (HSS - normal saline) was 5.4 mm Hg (95% confidence interval, 2.2 to 8.6; p = .002), and mean difference in cardiac index change, measured as the area under the curve for the whole study period, corresponded to 0.2 L.min.m (95% confidence interval, 0.03 to 0.4; p = .025). CONCLUSIONS: In this placebo-controlled study involving spontaneous subarachnoid hemorrhage patients with normal to moderately increased ICP, 2 mL/kg HSS reduced ICP and increased cerebral perfusion pressure significantly. Maximum effect was reached at twice the infusion time of 30 mins. There were also beneficial hemodynamic effects with increased cardiac index in the HSS group.     

Chronic pain and sensory changes after augmentation mammoplasty: long term effects of preincisional administration of methylprednisolone

We studied the prevalence of chronic pain and long term sensory changes after cosmetic augmentation mammoplasty and the effects of a single i.v. preoperative dose of methylprednisolone 125 mg (n=74), parecoxib 40 mg (n=71), or placebo (n=74). A questionnaire was mailed 6 weeks and 1 year after surgery. Response rate after 1 year was 80%. At 1 year non-evoked pain was present in 13%, and evoked pain was present in 20% with no statistically significant differences between the groups. Methylprednisolone was associated with reduced odds for hyperesthesia at 1 year (OR 0.3, 95% CI 0.1-0.6), and significantly reduced the prevalence of hyperesthesia (30%) compared with placebo (56%, P<0.01) and parecoxib (51%, P<0.04). Factors associated with increased odds for pain at 1 year were intensity of pain during the first 6 days after surgery (OR 1.3, 95% CI 1.1-1.6), pain at 6 weeks (OR 18.4, 95% CI 6.9-49.3), hyperesthesia at 6 weeks (OR 2.3, 95% CI 1.1-5.1) and present hyperesthesia (OR 3.1, 95% CI 1.4-6.7). We conclude that persistent pain and sensory changes are common after augmentation mammoplasty, and that patients having pain at 6 weeks most likely will have pain also at 1 year. Acute postoperative pain, hyperesthesia at 6 weeks, and the presence of hyperesthesia increased the odds for pain at 1 year. Preoperative methylprednisolone resulted in significantly less hyperesthesia compared with both parecoxib and placebo, but did not significantly reduce the prevalence of persistent spontaneous or evoked pain.     

Hypertension prevalence and diminished blood pressure–related hypoalgesia in individuals reporting chronic pain in a general population: The Tromsø Study

Resting blood pressure (BP) is inversely related to pain sensitivity in individuals free of chronic pain, reflecting homeostatic interactions between cardiovascular and pain modulatory systems. Several laboratory studies indicate that BP-related hypoalgesia is diminished in chronic pain patients, suggesting dysfunction in these interacting systems. Separate epidemiological findings reveal elevated hypertension prevalence in the chronic pain population. This study for the first time simultaneously evaluated both hypertension prevalence and BP-related hypoalgesia as they relate to chronic pain in the same sample. Resting BP and pain sensitivity were evaluated in a large general population sample (n = 10,135, aged 30–87 years). Subjects participated in a standardized 106 s cold pressor test, providing pain ratings at 9 s intervals. Self-reported presence of chronic pain and history of hypertension and use of antihypertensive medication were assessed. Significant interactions between chronic pain status and resting systolic (P < .001) and diastolic BP (P < .001) on mean pain ratings were observed. These interactions were due to significant (P < .001) BP-related hypoalgesia in individuals free of chronic pain that was twice the magnitude of the hypoalgesia observed in the group reporting chronic pain. Presence of chronic pain was associated with significantly increased odds of comorbid hypertension (P < .001). Within the chronic pain group, higher chronic pain intensity was a significant predictor of positive hypertension status beyond the effects of traditional demographic risk factors (P < .05). Results are consistent with the hypothesis that increased hypertension risk in the chronic pain population might be linked in part to chronic pain–related dysfunction in interacting cardiovascular–pain modulatory systems.     

Identification of genes particularly sensitive to lipopolysaccharide (LPS) in human monocytes induced by wild-type versus LPS-deficient Neisseria meningitidis strains

Lipopolysaccharide (LPS) in the outer membrane of Neisseria meningitidis plays a dominant role as an inflammation-inducing molecule in meningococcal disease. We have used microarray analysis to study the global gene expression after exposure of human monocytes for 3 h to wild-type N. meningitidis (10(6)), LPS-deficient N. meningitidis (10(6) and 10(8)), and purified N. meningitidis LPS (1 ng [33 endotoxin units]/ml) to identify LPS-inducible genes. Wild-type N. meningitidis (10(6)) induced 4,689 differentially expressed genes, compared with 72 differentially expressed genes induced by 10(6) LPS-deficient N. meningitidis organisms. However, 10(8) LPS-deficient N. meningitidis organisms induced 3,905 genes, indicating a dose-response behavior of non-LPS cell wall molecules. A comparison of the gene expression patterns from 10(6) wild-type N. meningitidis and 10(8) LPS-deficient N. meningitidis organisms showed that 2,401 genes in human monocytes were not strictly LPS dependent. A list of "particularly LPS-sensitive" genes (2,288), differentially induced by 10(6) wild-type N. meningitidis but not by 10(8) LPS-deficient N. meningitidis organisms, showed an early expression of beta interferon (IFN-beta), most likely through the Toll-like receptor-MyD88-independent pathway. Subsequently, IFN-beta may activate the type I IFN signaling pathway, and an unknown number of IFN-beta-inducible genes, such as those for CXCL9, CXCL10, CXCL11, IFIT1, IFIT2, IFIT3, and IFIT5, are transcribed. Supporting this, human monocytes secreted significantly higher levels of CXCL10 and CXCL11 when stimulated by 10(6) wild-type N. meningitidis organisms than when stimulated by 10(8) LPS-deficient N. meningitidis organisms. Plasma CXCL10, but not CXCL11, was positively correlated (r = 0.67; P < 0.01) to LPS in patients (n = 24) with systemic meningococcal disease. Thus, new circulating biomarkers in meningococcal disease may be suggested through LPS-induced gene expression changes in human monocytes.     

Critical Roles of Complement and Antibodies in Host Defense Mechanisms against Neisseria meningitidis as Revealed by Human Complement Genetic Deficiencies

Certain complement defects are associated with an increased propensity to contract Neisseria meningitidis infections. We performed detailed analyses of complement-mediated defense mechanisms against N. meningitidis 44/76 with whole blood and serum from two adult patients who were completely C2 or C5 deficient. The C5-deficient patient and the matched control were also deficient in mannose-binding lectin (MBL). The proliferation of meningococci incubated in freshly drawn whole blood was estimated by CFU and quantitative DNA real-time PCR. The serum bactericidal activity and opsonophagocytic activity by granulocytes were investigated, including heat-inactivated postvaccination sera, to examine the influence of antimeningococcal antibodies. The meningococci proliferated equally in C2- and C5-deficient blood, with a 2 log₁₀ increase of CFU and 4- to 5-log₁₀ increase in DNA copies. Proliferation was modestly decreased in reconstituted C2-deficient and control blood. After reconstitution of C5-deficient blood, all meningococci were killed, which is consistent with high antibody titers being present. The opsonophagocytic activity was strictly C2 dependent, appeared with normal serum, and increased with postvaccination serum. Serum bactericidal activity was strictly dependent on C2, C5, and high antibody titers. MBL did not influence any of the parameters observed. Complement-mediated defense against meningococci was thus dependent on the classical pathway. Some opsonophagocytic activity occurred despite low levels of antimeningococcal antibodies but was more efficient with immune sera. Serum bactericidal activity was dependent on C2, C5, and immune sera. MBL did not influence any of the parameters observed.Systemic meningococcal disease evolves when pathogenic Neisseria meningitidis breach the pharyngeal mucosa and start proliferating in the circulation (36, 44). The majority of the patients develops low-grade bacteremia leading to meningitis with a comparatively low case-fatality rate if adequate antibiotic treatment is given early (44). A minority develops fulminant sepsis caused by massive bacterial proliferation in the circulation, resulting in a very high case-fatality rate (44). A number of genetic disorders and polymorphisms in the host that influence the clinical presentation and outcome have been implicated in the response to intruding meningococci (4, 9).The complement system plays a crucial part in the host defense against systemic meningococcal disease (39). Acquisition of serum bactericidal antibodies correlates with protection (14, 16), whereas other mechanisms, primarily opsonophagocytosis, may also be important (1, 47). Deficiencies of the complement system affecting the alternative pathway, C3, and the terminal pathway have for a long time predominantly been associated with increased susceptibility to meningococcal disease (12, 13). Also, the rather common deficiency of mannose-binding lectin (MBL) has been associated with meningococcal disease, but only in early childhood (8, 11, 15, 19, 45). C2 deficiency, which apart from MBL deficiency is the most common inherited complement deficiency affecting about 1/20,000 of Caucasians (41), appears to be associated with a wide range of infections with encapsulated bacteria of which Streptococcus pneumoniae is the most frequent causative agent, whereas infections due to N. meningitidis occur less frequently (12, 25).In the present study blood samples from two individuals being genetically completely deficient in complement factor 2 (C2) or complement factor 5 (C5) and MBL were used to examine details regarding the specific roles of different parts of the complement system in the protection against serogroup B meningococcal disease. Bacterial survival and proliferation was examined in freshly drawn whole blood. Opsonophagocytic activity (OPA) and serum bactericidal activity (SBA), as well as the role of antimeningococcal antibodies, were studied separately. Functionally active and highly purified complement components were used for reconstitution experiments both of whole blood and of serum in order to confirm the specific roles of these components.