Expression and regulation of antimicrobial peptide rCRAMP after bacterial infection in primary rat meningeal cells

Bacterial meningitis is characterized by an inflammation of the meninges and continues to be an important cause of mortality and morbidity. Meningeal cells cover the cerebral surface and are involved in the first interaction between pathogens and the brain. Little is known about the role of meningeal cells and the expression of antimicrobial peptides in the innate immune system. In this study we characterized the expression, secretion and bactericidal properties of rat cathelin-related antimicrobial peptide (rCRAMP), a homologue of the human LL-37, in rat meningeal cells after incubation with different bacterial supernatants and the bacterial cell wall components lipopolysaccharide (LPS) and peptidoglycan (PGN). Using an agar diffusion test, we observed that supernatants from meningeal cells incubated with bacterial supernatants, LPS and PGN showed signs of antimicrobial activity. The inhibition of rCRAMP expression using siRNA reduced the antimicrobial activity of the cell culture supernatants. The expression of rCRAMP in rat meningeal cells involved various signal transduction pathways and was induced by the inflammatory cytokines interleukin-1, -6 and tumor necrosis factor alpha. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae and rCRAMP was localized in meningeal cells using immunohistochemistry. These results suggest that cathelicidins produced by meningeal cells play an important part in the innate immune response against pathogens in CNS bacterial infections.

Clinical radiology and postmortem imaging (Virtopsy) are not the same: Specific and unspecific postmortem signs

The aim of this article is to disclose the characteristics of postmortem forensic imaging; give an overview of the several possible findings in postmortem imaging, which are uncommon or new to clinical radiologists; and discuss the possible pitfalls. Unspecific postmortem signs are enlisted and specific signs shall be presented, which are typical for one cause of death. Unspecific signs. Livor mortis may not only be seen from the outside, but also inside the body in the lungs: in chest CT internal livor mortis appear as ground glass opacity in the dependent lower lobes. The aortic wall is often hyperdense in postmortem CT due to wall contraction and loss of luminal pressure. Gas bubbles are very common postmortem due to systemic gas embolism after major open trauma, artificial respiration or initial decomposition; in particular putrefaction produces gas bubbles globally. Specific signs. Intracranial bleeding is hyperattenuating both in radiology and in postmortem imaging. Signs of strangulation are hemorrhage in the soft tissue of the neck like skin, subcutaneous tissue, platysma muscle and lymph nodes. The "vanishing" aorta is indicative for exsanguination. Fluid in the airways with mosaic lung densities and emphysema (aquosum) is typical for fresh-water drowning.

Communicative Signs Meaning Naturally

Paul Grice distinguishes between natural meaning and non-natural meaning, where the first notion is especially connected to something’s being a natural sign and the second to communication. It is argued that some of the arguments against the distinction being exhaustive are based on a misinterpretation of Grice, but also that the distinction cannot be exhaustive if one takes into account both the criterion of factivity and the connection to communication. If one makes a distinction between natural and non-natural communication, then there are different types of natural communication to be distinguished: goal-directed communication, intentional communication and open intentional communication. Given the empirical evidence, the behavior of chimpanzees and of human infants may be described as goal-directed communication, but there are also important differences between the communicative behavior of the two.

Distinct proteinase K-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrP(res)) in a highly scrapie-affected goat flock in Greece. The PrP(res) profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrP(res) fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrP(res) phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder.

Unusual systemic signs in a dog with sterile neutrophilic-macrophagic lymphadenitis and nodular panniculitis

A 7 mo old female English springer spaniel was presented with diarrhea, vomiting, apathy, and hyperthermia. Further examinations revealed generalized lymphadenomegaly consistent with sterile neutrophilic-macrophagic lymphadenitis and pulmonary involvement. Subcutaneous nodules developed one day after presentation. Histology was consistent with sterile idiopathic nodular panniculitis and vasculitis. No infectious organism was isolated. The dog responded to prednisolone, but relapsed during medication tapering. Cyclosporine had to be added to control the disease. No further relapse had occurred 98 wk after the first presentation. This is an unusual presentation of a systemic sterile neutrophilic-macrophagic lymphadenitis with nodular panniculitis and vasculitis associated with gastrointestinal and pulmonary signs.

Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families

REASONS FOR PERFORMING STUDY: The horse owner assessed respiratory signs index (HOARSI-1-4, healthy, mildly, moderately and severely affected, respectively) is based on owner-reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in-depth examination of the lower respiratory tract has not been investigated. OBJECTIVES: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI-2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. METHODS: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI-1-4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. RESULTS: HOARSI-3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper-responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. CONCLUSIONS AND CLINICAL RELEVANCE: HOARSI reliably identifies RAO-affected horses in our population.

Severe signs of hyponatremia secondary to desmopressin treatment for enuresis: A systematic review

OBJECTIVE: Dilutional hyponatremia is a serious adverse effect of desmopressin, a vasopressin analog that is widely prescribed to manage monosymptomatic enuresis. The presentation of hyponatremia, largely related to cerebral dysfunction, can include severe signs like altered mental status and seizures. METHODS: We reviewed the literature dealing with altered mental status or seizures in enuretic subjects on desmopressin. The retained publications included patients who were described individually, revealing data on mode of administration, further identifiable factors predisposing to hyponatremia, presentation and clinical course. RESULTS: We found 54 cases of hyponatremia secondary to desmopressin treatment presenting with altered mental status or seizures. In most cases the complication developed 14 days or less after starting desmopressin. An intranasal formulation had been used in 47 patients. Excess fluid intake was documented as a contributing factor in at least 22 cases. In 6 cases severe signs of hyponatremia developed in the context of intercurrent illnesses. CONCLUSION: Altered mental status or seizures are very rare but recognized complications of desmopressin in enuresis. This complication mostly develops in subjects managed with the intranasal formulation 14 days or less after starting the medication, following excess fluid intake and during intercurrent illnesses.

Isolated Rosai-Dorfman disease of intracranial meninges

Rosai-Dorfman disease (RDD) is a non-neoplastic proliferative histiocytic disorder that primarily affects lymph nodes (sinus histiocytosis with massive lymphadenopathy). Primary RDD of the central nervous system is most uncommon. We report on a 35-year-old man with isolated RDD of the meninges overlying the left cerebral hemisphere. Presenting signs and symptoms included severe progressive ipsilateral headaches of 4 months duration, as well as laboratory evidence of mild non-specific systemic inflammatory reaction. On magnetic resonance imaging, the lesion was seen as a contrast-enhancing, plaque-like thickening of the dura mater over the left convexity,without impinging on adjacent bone or cerebral parenchyma. Meningeal biopsy revealed a mixed mononuclear infiltrate dominated by CD68(+), S100(+), CD1a(-) non-Langerhans type histiocytes on a background of fibrosis. Bacteria, in particular mycobacteria, and fungi were excluded with special stains. Extensive clinical workup, encompassing computed tomography of thoracal and abdominal organs, bone marrow biopsy, and bronchoalveolar lavage failed to reveal any extracranial involvement. Laboratory tests for autoimmunity, including C- and P-antineutrophil cytoplasmic antibodies, antinuclear antibody, and serum rheumatoid factor, were negative. Methylprednisolone therapy induced complete remission of symptoms, with the neuroradiologic status remaining unchanged on follow-up after 2 months. We discuss the complex clinicopathologic differential diagnosis and therapeutic issues of this rare condition. While the correct diagnosis of central nervous system RDD is unlikely to be established without invasive procedures (biopsy), a conservative therapeutic approach may be considered a legitimate option.

Variable ECG signs of ischemia during controlled occlusion of the left and right coronary artery in humans

Infarct size (IS) increases with vascular occlusion time, area at risk for infarction, lack of collateral supply, absence of preconditioning, and myocardial demand for O2 supply. ECG S-T segment elevation is used as a measure of severity of ischemia and a surrogate for IS. This study in 50 patients with coronary artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to determine whether S-T segment elevation, corrected for the above-mentioned variables, in the left coronary artery (LCA group, n = 36) is different from that in the right coronary artery (RCA group, n = 14) territory. After consideration of all known determinants of IS, particularly mass at risk and collateral supply, the LCA territory is more sensitive than the RCA region to a 2-min period of myocardial ischemia.

Multiple spinal extradural meningeal cysts presenting as acute paraplegia. Case report and review of the literature

Multiple spinal extradural meningeal cysts are rare. To the authors' knowledge, there have been only four reported cases in the world literature. The authors report a case of multiple spinal extradural meningeal cysts in a 31-year-old woman presenting with acute paraplegia. Magnetic resonance imaging of the thoracolumbar spine revealed multiple extradural cystic lesions extending from T-7 to T-8 and from T-12 to L-3. Intraoperative findings demonstrated a white, fibrous, and tense cyst filled with cerebrospinal fluid-like colorless fluid. Excision of the posterior wall of the symptomatic cyst was followed by immediate neurological improvement. The examination of the pathological specimen showed a thick duralike layer of collagen and an inner membrane of arachnoid that is often not found in these lesions. The final diagnosis was based on combined imaging, intraoperative, and histopathological findings. The authors review the literature and discuss the etiological, diagnostic, and therapeutic aspects of this lesion.

EEG signs of vigilance fluctuations preceding perceptual flips in multistable illusionary motion

This EEG study was performed to clarify the time course of brain electrical events and possible vigilance changes associated with perceptual flips during multistable perception. 13 healthy subjects (28.5 3.8 years) were recorded with a 21-channel digital EEG during a stroboscopic alternative motion paradigm implying illusionary motion with ambiguous direction. Perceptual flips were preceded by a significant decrease of EEG frequencies, and followed by a significant frequency increase with a trend to overshoot. EEG slowing is a reliable sign of vigilance decrease and can be related to thalamic deactivation. This is consistent with a recent fMRI study, which showed thalamic deactivation associated with perceptual flips. The study added important chronological information about this phenomenon and allows the conclusion that reduced vigilance facilitates perceptual discontinuities during multistable perception.