Normalized serum eosinophil peroxidase levels are inversely correlated with esophageal eosinophilia in eosinophilic esophagitis.

Eosinophil peroxidase is an eosinophil-specific, cytoplasmic protein stored in the secondary granules of eosinophils. While eosinophil peroxidase deposition is increased in the esophagus in eosinophilic esophagitis (EOE), its potential role as a peripheral marker is unknown. This study aims to examine the relationship between serum eosinophil peroxidase and esophageal eosinophilia in eosinophilic esophagitis. Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for serum eosinophil peroxidase, eosinophilic cationic protein, and eosinophil derived neurotoxin using ELISA. Matching esophageal tissue sections were stained and assessed for eosinophil peroxidase deposition using a histopathologic scoring algorithm. Mean peripheral blood absolute eosinophil counts in eosinophilic esophagitis subjects were significantly elevated compared to controls (363 vs. 195 cells/µL, P = 0.008). Absolute median serum eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin did not differ between groups; however, when normalized for absolute eosinophil counts, eosinophilic esophagitis subjects had significantly lower median eosinophil peroxidase levels (2.56 vs. 6.96 ng/mL per eos/µL, P = 0.002, AUC 0.79 (0.64, 0.94 95% CI)). Multivariate analysis demonstrated this relationship persisted after controlling for atopy. Esophageal biopsies from eosinophilic esophagitis subjects demonstrated marked eosinophil peroxidase deposition (median score 46 vs. 0, P < 0.0001). Normalized eosinophil peroxidase levels inversely correlated with esophageal eosinophil density (r = -0.41, P = 0.009). In contrast to marked tissue eosinophil degranulation, circulating eosinophils appear to retain their granule proteins in EoE. Investigations of normalized serum eosinophil peroxidase levels as a biomarker of EoE are ongoing.

Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.

BACKGROUND: Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. METHODS: Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. RESULTS: In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. CONCLUSION: The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.

Re-defining the unique roles for eosinophils in allergic respiratory inflammation.

The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodelling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) the initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) the suppression Th1/Th17 pathways in lung-draining lymph nodes, (iii) the recruitment of effector Th2 T cells to the lung, and finally, (iv) mechanisms of inflammatory resolution that re-establish pulmonary homoeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC) and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homoeostatic baseline. In this review, we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung following allergen provocation.

Eosinophil activities modulate the immune/inflammatory character of allergic respiratory responses in mice.

BACKGROUND: The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animal models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. METHODS: We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. RESULTS: Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyper-responsiveness in response to methacholine indistinguishable from eosinophilic wild-type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon the restoration of peripheral eosinophils. CONCLUSIONS: Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not to the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses.

Eosinophils in health and disease: the LIAR hypothesis.

Discussions of eosinophils are often descriptions of end-stage effector cells with destructive capabilities mediated predominantly by released cytotoxic cationic granule proteins. Moreover, eosinophils in the medical literature are invariably associated with the pathologies linked with helminth infections or allergic diseases such as asthma. This has led to an almost fatalist view of eosinophil effector functions and associated therapeutic strategies targeting these cells that would make even William of Ockham proud - eosinophil effector functions have physiological consequences that increase patient morbidity/mortality and 'the only good eosinophils are dead eosinophils'. Unfortunately, the strengths of dogmas are also their greatest weaknesses. Namely, while the repetitive proclamation of dogmatic concepts by authoritative sources (i.e. reviews, meeting proceedings, textbooks, etc.) builds consensus within the medical community and lower the entropies surrounding difficult issues, they often ignore not easily explained details and place diminished importance on alternative hypotheses. The goal of this perspective is twofold: (i) we will review recent observations regarding eosinophils and their activities as well as reinterpret earlier data as part of the synthesis of a new paradigm. In this paradigm, we hypothesize that eosinophils accumulate at unique sites in response to cell turnover or in response to local stem cell activity(ies). We further suggest that this accumulation is part of one or more mechanisms regulating tissue homeostasis. Specifically, instead of immune cells exclusively mediating innate host defence, we suggest that accumulating tissue eosinophils are actually regulators of Local Immunity And/or Remodeling/Repair in both health and disease - the LIAR hypothesis; (ii) we want to be inflammatory (pun intended!) and challenge the currently common perspective of eosinophils as destructive end-stage effector cells. Our hope is to create more questions than we answer and provoke everyone to spend countless hours simply to prove us wrong!

Introduction of endovascular embolization for intracranial aneurysms in a low-volume institution.

BACKGROUND: Studies indicate a relationship between hospital caseload and health outcomes after both surgical and endovascular repair of intracranial aneurysms. PURPOSE: To evaluate outcomes after introduction of endovascular embolization for intracranial aneurysms in a low-volume regional university hospital. MATERIAL AND METHODS: Retrospective study of 243 consecutive patients treated for 284 intracranial aneurysms with endovascular embolization or surgical clipping from 2000 to 2006 at the University Hospital of North Norway. Postoperative complications were registered. The Glasgow Outcome Scale (GOS) was used for assessment of outcome. RESULTS: The mean annual number of procedures was 39 (microsurgery 23, embolization 16). Seventy-four percent of patients with ruptured aneurysms and all patients with unruptured aneurysms had a favorable outcome (GOS 4 or 5) at 1 year follow-up. Patients with subarachnoid hemorrhage were more likely to experience postoperative complications than patients treated for unruptured aneurysms (42% versus 8% of the patients, P<0.01). The immediate incomplete occlusion rate (Raymond II-III) in the initial embolization procedure was 29%. Ten endovascularly treated patients and one surgically treated patient required retreatments due to residual aneurysm or neck remnants. CONCLUSION: The present study indicates that acceptable outcome from aneurysm treatment, both endovascular and microsurgical, is possible in a low-volume institution.

Detection of cerebral embolic signals in patients with systemic lupus erythematosus.

BACKGROUND: Involvement of the CNS in systemic lupus erythematosus (SLE) is caused by several pathogenic mechanisms including cerebral embolism. AIM: To measure the frequency of microembolic signals (MES) by using transcranial Doppler (TCD) ultrasound and to assess their association with cerebral infarction, neuropsychological dysfunction, and biochemical, sonographic and clinical variables in an unselected group of patients with SLE. METHODS: A 1-h TCD recording from the middle cerebral artery was carried out in 55 patients with SLE having a mean age of 46 (SD 13) years. MRI of the brain, carotid artery ultrasonography with intima-media thickness and atherosclerotic plaque assessments were carried out in addition to a broad biochemical and clinical assessment. All patients underwent a neuropsychological assessment. RESULTS: Of the 55 patients, MES were detected in 5 (9%) and cerebral infarcts were found in 9 (18%). A significant association was found between MES and cerebral infarcts and considerably more neuropsychological deficits were found in MES-positive patients compared with the negative group. MES were not associated with other clinical, sonographic and biochemical factors believed to be associated with cerebral embolism. CONCLUSIONS: Cerebral embolism may be one of the important mechanisms responsible for the high prevalence of cerebrovascular events and the neuropsychological deficits observed in patients with SLE. Although the number of MES-positive patients was small, the lack of a significant association between MES and other known risk factors for MES suggests a complex pathogenesis for the embolisation in these patients.

Gliosarcoma with liposarcomatous component, bone infiltration and extracranial growth.

Gliosarcoma is a highly malignant brain tumor consisting of both a glioblastoma and a mesenchymal component. The latter typically resembles fibrosarcoma, but differentiation patterns resembling osteosarcoma, chondrosarcoma, angiosarcoma and rhabdomyosarcoma have also been described. Molecular-genetic studies have shown that both glioblastoma and the mesenchymal component share identical cytogenetic abnormalities or mutations, suggesting a monoclonal origin from glial cells. We report an unusual case of gliosarcoma that presented as a large intracerebral tumor with infiltration of the temporal bone and the soft tissues in the infratemporal fossa. Microscopically, the tumor consisted of alternating areas of glioblastoma and fibrosarcoma. Focally, areas ofosteosarcomatous and liposarcomatous differentiation were found. Although gliosarcoma with transcranial penetration is very rare, it should be suspected in case of intracranial tumor with glioblastoma-imaging features, infiltration of bone and extracranial growth. Our case of liposarcomatous differentiation in gliosarcoma--together with another very recently reported similar case--expands the morphologic heterogeneity of this peculiar brain tumor.

Single-Layer WEBs: Intrasaccular Flow Disrupters for Aneurysm Treatment­Feasibility Results from a European Study.

BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use. MATERIALS AND METHODS: Data from all consecutive patients treated with a single-layer WEB device, in 10 European centers from June 2013 to May 2014 were included. Clinical presentations, technical details, intra- and perioperative complications, and outcomes at discharge were recorded. Clinical and angiographic data at last follow-up were also analyzed when available. RESULTS: Ninety patients with 98 WEB-treated aneurysms were included in this study. In 93 cases (95%), WEB placement was possible. Complete occlusion at the end of the procedure was obtained in 26 instances (26%). Additional treatment during the procedure (coiling and/or stent placement) was necessary in 12 cases (12.7%). Procedure-related complications occurred in 13 cases, leading to permanent neurologic deficits in 4 patients (4.4%). Early vascular imaging follow-up data were available for 44 patients (57%), with an average time interval of 3.3 months. Treatment-related morbidity and mortality rates at last follow-up were 2.2% and 1.1%, respectively. CONCLUSIONS: In this study, the feasibility and safety of the single-layer WEB device was comparable with that of the double-layer. However, further studies are needed to evaluate long-term efficacies.

Pilomatrix carcinoma with multiple metastases: report of a case and review of the literature.

Pilomatrix carcinoma, the malignant counterpart of pilomatrixoma, is rare, with only 55 cases reported, and only four cases with visceral metastases described in the literature. Here we present a case report and a literature review on this rare tumour. A 74-year-old male with a pilomatrix carcinoma from the left temporal region presented in July 1996 and the tumour was excised. One month after diagnosis, metastases to both lungs and to a regional lymph node were found and histologically verified. The patient also developed metastases in the abdomen, back and thoracic spine. The latter resulted in spinal cord compression and paraplegia. Despite systemic chemotherapy with intravenous cisplatin and 5-fluorouracil and localised radiotherapy to the thoracic spine, progression and deterioration led to death within 3 months from time of diagnosis. Pilomatrix carcinomas are usually indolent. In our patient, however, the malignant disease progressed rapidly and it appeared to be resistant to both chemotherapy and irradiation.

Sodium addition to nonionic contrast media. Effects on cardiac monophasic action potentials and hemodynamics in a dog model.

In order to study the electrophysiologic and hemodynamic effects of sodium addition to low-osmolality contrast media during coronary arteriography, eight dogs with surgically opened thoraces were studied. Epicardial monophasic action potentials (MAP) were recorded from the contrast perfused area, using suction electrodes. Six milliliters of iohexol, iohexol with addition of 20 to 80 mmol/L Na+ and ioxaglate, were selectively administered into the left coronary artery. Only minor hemodynamic alterations occurred with the iohexol solutions, whereas ioxaglate decreased left ventricular (LV) inotropy and pressures initially. Iohexol and iohexol containing less than 40 mmol/L Na+ did not change MAP duration significantly. The addition of 80 mmol/L Na+ to iohexol lengthened MAP duration at 25%, 50%, and 90% repolarization by 14 +/- 2, 18 +/- 3, and 18 +/- 5 mseconds, respectively. Ioxaglate lengthened MAP duration by 14 +/- 3, 17 +/- 3, and 26 +/- 8 mseconds, respectively. Thus, during coronary arteriography in dogs, iohexol with sodium added, like ioxaglate, induced regional electrophysiologic changes in the contrast-perfused area of the myocardium, while sodium-free iohexol did not.

Repeated intracoronary injections of contrast media. Additive hemodynamic and electrophysiologic effects in a dog model.

RATIONALE AND OBJECTIVES: Coronary arteriography in patients implies several selective injections into the coronary arteries. The authors investigate whether repeated injections cause additive cardiac hemodynamic and electrophysiologic effects in dogs. METHODS: Five repeated injections of 5 mL iohexol (Omnipaque 350 mgI/mL, Nycomed Imaging AS, Oslo, Norway), ioxaglate (Hexabrix 320 mgI/mL, Laboratory Guerbet, Cedex, France), and sodium meglumine-diatrizoate (Renografin-76 370 mgI/mL, Squibb Diagnostics, Princeton, NJ) were given into the left coronary artery in 7 anesthetized dogs and were compared with the effects after a 5 mL single injection of the same medium. Left ventricular (LV) pressures, LV dP/dtmax (inotropy) and epicardial monophasic action potential were recorded, from which monophasic action potential duration (MAPD) was measured. RESULTS: Repeated injections of ioxaglate and sodium meglumine-diatrizoate did not potentiate initial decrease in LV pressures and inotropy, but the secondary increase in LV inotropy increased more after repeated injections than after a single injection. Repeated injections of iohexol increased LV inotropy more than a single injection. All contrast media prolonged MAPD more after repeated injections than after single injections. MAPD was prolonged 30 sec after the last injection. CONCLUSION: Repeated injections of contrast media cause greater cardiac hemodynamic and electrophysiologic effects than a single injection during selective coronary arteriography.

The effect of the temperature of contrast media on cardiac electrophysiology and hemodynamics during coronary arteriography.

RATIONALE AND OBJECTIVES: The authors assess the effect of preheating ionic and nonionic contrast media on regional electrophysiologic and/or hemodynamic side effects during coronary arteriography. METHODS: The authors injected 6 mL of nonionic (iohexol) and ionic (ioxaglate) low-osmolality contrast media and NaCl 0.9% twice, at 20 degrees C and 37 degrees C, into the left coronary artery in eight open-chest dogs. To study regional electrophysiologic effects, the authors measured monophasic action potential duration (MAPD) using an epicardial suction electrode placed in the contrast-perfused area. Hemodynamic effects were studied by recording left ventricular systolic pressure (LVSP), mean aortic pressure, LV end diastolic pressure (LVEDP), LV dP/dtmax, and cardiac output. RESULTS: Ioxaglate and iohexol prolonged MAPD more at 20 degrees C than at 37 degrees C. NaCl 0.9% prolonged MAPD only when injected at 20 degrees C. The temperature of iohexol did not significantly influence LV pressures (LVPs) or LV dP/dtmax. Ioxaglate increased LVEDP and decreased LV dP/dtmax more at 20 degrees C than at 37 degrees C 10 seconds after injection. CONCLUSIONS: In dogs, contrast media, preheated to body temperature before selective injection during coronary arteriography, reduced dispersion of repolarization and reduced the risk of serious cardiovascular complications.

Cerebral computed tomography and electroencephalography compared with neuropsychological findings in systemic lupus erythematosus.

Central nervous system involvement was evaluated in 36 patients with systemic lupus erythematosus (SLE) using cerebral computed tomography (CT), electroencephalography (EEG), and a neuropsychological test battery. The purpose was to investigate whether brain dysfunction as assessed by comprehensive neuropsychological investigation is associated with findings of routine investigation methods such as CT and EEG which are available in most hospitals. Abnormal EEG was found in 19%, and CT revealed cerebral atrophy in 47% of SLE patients. Few neuropsychological functions were affected by the presence of abnormal EEG, cerebral atrophy, or infarcts. Significant associations were found only between cortical atrophy and impairment of tactile spatial problem-solving and motor dexterity, and between cortical infarcts and motor dexterity in the dominant hand. The value of conventional EEG in assessing cerebral SLE is negligible, except for identifying epileptic activity and focal pathology. Cerebral CT has little relevance in predicting brain dysfunction as established by neuropsychological assessment in SLE, except for detecting cortical atrophy and infarcts.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Imaging findings in schwannomas of the jugular foramen.

BACKGROUND AND PURPOSE: Tumors of the cranial nerve sheath constitute 5% to 10% of all intracranial neoplasms, yet few articles have described their CT and MR characteristics. We report the imaging findings in a relatively large series of schwannomas of the jugular foramen, contrasting them with other disease entities, especially vestibular schwannomas and tumors of the glomus jugulare. METHODS: CT and/or MR studies of eight patients who underwent surgery for histologically proved schwannomas were reviewed retrospectively. One additional patient with an assumed schwannoma of the jugular foramen, who did not have surgery, was also included. RESULTS: Surgical findings showed schwannomas of the glossopharyngeal nerve in seven patients and tumor involvement of both the glossopharyngeal and vagal nerves in one patient. All tumors were partially located within the jugular foramen. Growth extending within the temporal bone was typical. Tumor extended into the posterior cranial fossa in all nine patients and produced mass effect on the brain stem and/or cerebellum in seven patients; in five patients, tumor extended below the skull base. On unenhanced CT scans, tumors were isodense with brain in six patients and hypodense in two. In seven patients, CT scans with bone algorithm showed an enlarged jugular foramen with sharply rounded bone borders and a sclerotic rim. On MR images, T1 signal from tumor was low and T2 signal was high relative to white matter in all patients. Contrast enhancement on CT and/or MR studies was strong in eight patients and moderate in one. CONCLUSION: Schwannoma of the jugular foramen is characteristically a sharply demarcated, contrast-enhancing tumor, typically centered on or based in an enlarged jugular foramen with sharply rounded bone borders and a sclerotic rim. Intraosseous extension may be marked.

Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome.

OBJECTIVE: The present study was conducted to validate S-100 protein as a marker of brain damage after minor head injury. METHODS: We studied 50 patients with minor head injuries and Glasgow Coma Scale scores of 13 to 15 in whom computed tomographic scans of the brain revealed no abnormalities. Serum levels of S-100 protein were measured at admittance and hourly thereafter until 12 hours after injury. Magnetic resonance imaging and baseline neuropsychological examinations were performed within 48 hours, and neuropsychological follow-up was conducted at 3 months postinjury. RESULTS: Fourteen patients (28%) had detectable serum levels of S-100 protein (mean peak value, 0.4 microg/L [standard deviation, +/- 0.3]). The S-100 protein levels were highest immediately after the trauma, and they declined each hour thereafter. At 6 hours postinjury, the serum level was below the detection limit (0.2 microg/L) in five (36%) of the patients with initially detectable levels. Magnetic resonance imaging revealed brain contusions in five patients, four of whom demonstrated detectable levels of S-100 protein in serum. The proportion of patients with detectable serum levels was significantly higher when magnetic resonance imaging revealed a brain contusion. In patients with detectable serum levels, we observed a trend toward impaired neuropsychological functioning on measures of attention, memory, and information processing speed. CONCLUSION: Determination of S-100 protein levels in serum provides a valid measure of the presence and severity of traumatic brain damage if performed within the first hours after minor head injury.

Coronary arteriography with an oxygenated contrast medium: cardiac effects in dogs with and without acute ischemic heart failure.

RATIONALE AND OBJECTIVES: We investigated the possible cardiac effects of oxygen addition to contrast media (CM) during coronary arteriography in dogs that did and did not have ischemic heart failure. METHODS: Acute ischemic heart failure was induced by injecting small plastic microspheres into the left coronary artery of 18 dogs. Hemodynamic and electrophysiologic measurements were performed during a single injection before and during heart failure and during a single injection and five rapidly repeated CM injections during heart failure. Iohexol supplemented with electrolytes (iohexol + electrolytes = IPE), oxygenated IPE (IPE+O), Ringer acetate, and oxygenated Ringer acetate were injected into the left coronary artery. RESULTS: Single injections of IPE and IPE+O induced small hemodynamic and electrophysiologic effects. However, repeated injections of IPE and IPE+O increased left ventricular inotropy (maximum value of the first derivative of the left ventricular pressure) by 36% and 39%, reduced heart rate by 7% (for both), and lengthened QTc time (corrected QT interval) by 39 and 38 msec, respectively. A comparison of IPE and IPE+O revealed no statistically significant differences. CONCLUSION: Although electrolyte addition to nonionic CM may reduce the risk of cardiac complications during coronary arteriography, oxygenation does not seem to significantly further reduce this risk.

Contrast media-induced ventricular fibrillation: an experimental study of the effects of dimeric contrast media during wedged catheter injection in dogs.

RATIONALE AND OBJECTIVES: We investigated the cardiac effects of an ionic dimer, ioxaglate and two nonionic dimers, iotrolan, and iodixanol. METHODS: During a simulated wedged catheter situation, 22 ml of each contrast medium was injected into the left anterior descending branch of the left coronary artery in seven open-chested, anesthetized dogs. RESULTS: Of 13 injections with each contrast medium, ioxaglate induced ventricular fibrillation in 11 after 34 +/- 5 sec, iotrolan in 6 after 42 +/- 4 sec, and iodixanol in 3 after 61 +/- 1 sec. Ioxaglate markedly lengthened monophasic action potential duration in contrast medium-perfused myocardium. Iotrolan, and iodixanol induced biphasic changes, first lengthening and then shortening action potential duration. The electrophysiological changes occurred later when using iodixanol. CONCLUSIONS: The risk of ventricular fibrillation during long-lasting contrast media exposure to the myocardium, as in a wedged catheter situation, appears to be much lower with iodixanol compared with ioxaglate and also lower than when using iotrolan.

Role of sodium addition to nonionic contrast medium in preventing ventricular fibrillation during coronary arteriography in dogs.

RATIONALE AND OBJECTIVES: We studied the effect of the addition of sodium to nonionic contrast medium (CM) on the incidence of ventricular fibrillation (VF) during coronary arteriography in dogs. METHODS: We infused 20 ml (0.5 ml/sec) of iohexol, iohexol plus 30 mmol of Na+ per liter, and NaCl-Ringer's acetate in randomized order through a wedged catheter placed in the right coronary artery (RCA) or in the left anterior descending coronary artery (LAD) in 12 anesthetized dogs. In addition to electrocardiographic and hemodynamic measurements, epicardial monophasic action potential durations and ventricular activation times were recorded during infusions into the LAD. RESULTS: All infusions with iohexol into the RCA and the LAD (n = 16) caused VF. Seven of 19 infusions with iohexol plus 30 mmol of Na+ per liter caused VF. Infusions with iohexol plus 30 mmol of Na+ per liter that did not cause VF lengthened monophasic action potential durations and increased ventricular activation times more in the CM-perfused area than in the control area. CONCLUSION: The addition of sodium to iohexol reduces the incidence of VF when infused through a wedged catheter. The protective mechanisms may be attributable to a lengthened repolarization phase and an increased activation time in the CM-perfused area.