Update on Whole-body MRI in Musculoskeletal Applications.

Whole-body magnetic resonance imaging (WB-MRI) is a powerful tool increasingly used to assess oncologic and nononcologic diseases. WB-MRI provides information about diffuse multifocal pathologies with excellent anatomical definition through high soft tissue contrast and spatial resolution as well as valuable functional information from diffusion-weighted images. In addition to its roles in establishing the diagnosis and assessing the extent and severity of disease, WB-MRI is also useful for monitoring the response to treatment for malignant and benign systemic diseases affecting the musculoskeletal system. This article reviews and updates the applications of WB-MRI in current practice, discussing the role of this helpful tool in various conditions involving the musculoskeletal system including bone metastases, hematologic cancers, inflammatory processes, infections, and multisystemic-multifocal bone, nerve, vascular, and muscle/soft tissue disorders, as well as other idiopathic conditions.

Risk factors and prognosis of vertebral compressive fracture in pyogenic vertebral osteomyelitis.

OBJECTIVES: To analyse the clinical, microbiological and radiological characteristics, and to identify risk factors of vertebral compressive fracture (VF) in spontaneous pyogenic vertebral osteomyelitis (VO). METHODS: A retrospective clinical study and blinded radiological review of adult patients with VO. RESULTS: Eighty-eight patients were included: 57 (65%) had a definitive diagnosis of VO (positive microbiology), and 31 (35%) had a probable diagnosis of VO. Of these, 27 (30.7%) presented with VF at diagnosis of VO, and 4 afterwards (total 31, 35.2%). Patients with VF were considered to be at higher risk of osteopenia--they were older (74 vs 66 years, p = 0.013), and included high percentage of women (33 vs 41%, NS)--; and presented more dorsal involvement (56 vs 21%; p < 0.007). Causal microorganisms were similar between groups (VF, no VF). The time to diagnosis of VO was longer in the presence of VF (65 vs 23 days, p = 0.001), and also in cases with no isolated organisms. All patients received antibiotics, and just one patient required spinal stabilisation (VF). After 357 median days of follow-up, all patients were cured. Clinical improvement (residual pain, functional recovery) tended to be slower in patients with VF (log-rank 0.19 and 0.15, respectively), but clinical symptoms were similar in most patients at the last follow-up (VF, no VF). CONCLUSIONS: VF is a common complication in pyogenic VO that causes slower clinical recovery. Risk factors of VF are: osteopenia, a delayed diagnosis and dorsal involvement. Conservative management is probably appropriate for most cases, but spinal stabilisation should be considered in some specific cases.

Current State and Proposal of Best Practices of Standardized Patients for Spanish-Language Objective Structured Clinical Encounters in US Medical Schools.

INTRODUCTION: Medical Spanish programs commonly engage Spanish-speaking standardized patients (SPs) for communication skills assessment, yet no studies address SP recruitment, selection, or training. METHODS: We sent questionnaires to medical Spanish faculty at 20 US medical schools to gauge their practices in recruiting and selecting Spanish-language SPs. We invited faculty to distribute a separate questionnaire to Spanish-language SPs to gather SP language abilities, training, and experience. We analyzed data using descriptive statistics and qualitative content analysis. When available, we reviewed SP video encounters to formally assess participating SPs' linguistic performance using the SP Oral Language Observation Matrix, a rating tool adapted from the Physician Oral Language Observation Matrix to assess oral medical Spanish proficiency. RESULTS: Eighty percent of faculty (16/20) responded. Standardized patient recruitment sources included institutional English-language SPs, Hispanic student groups and professional organizations, communities, and language professionals. Faculty-reported strategies to determine language readiness included interviewing SP candidates in Spanish and asking them to self-rate language skills using a validated scale. Fifteen SPs (54%, 15/28) from 5 schools responded to the SP questionnaire, and one third (5/15) reported that their Spanish was not assessed before being selected as an SP. In addition, one third (5/15) did not receive any initial training before performing a medical Spanish case. Raters assessed 11 different SPs using the SP Oral Language Observation Matrix, and 6 were rated as linguistically "ready" for the SP role. CONCLUSIONS: Current approaches to recruitment, training, and language assessment of SPs vary. We propose strategies to ensure that medical Spanish encounters authentically reflect Spanish-speaking patients.

A Thermographic Disease Activity Index for remote assessment of rheumatoid arthritis.

OBJECTIVES: Remote assessment of patients with rheumatoid arthritis (RA) has increased during recent years. However, telematic consultations preclude the possibility of carrying out a physical examination and obtaining objective inflammation. In this study, we developed and validated two novel composite disease activity indexes (Thermographic Disease Activity Index (ThermoDAI) and ThermoDAI-CRP) based on thermography of hands and machine learning, in order to assess disease activity easily, rapidly and without formal joint counts. METHODS: ThermoDAI was developed as the sum of Thermographic Joint Inflammation Score (ThermoJIS), a novel joint inflammation score based on the analysis of thermal images of the hands by machine learning, the Patient Global Assessment (PGA) and, for ThermoDAI-CRP, the C reactive protein (CRP). Construct validity was tested in 146 patients with RA by using Spearman's correlation with ultrasound-determined grey-scale synovial hypertrophy (GS) and power Doppler (PD) scores, CDAI, SDAI and DAS28-CRP. RESULTS: Correlations of ultrasound scores with ThermoDAI (GS=0.52; PD=0.56) and ThermoDAI-CRP (GS=0.58; PD=0.61) were moderate to strong, while the correlations of ultrasound scores with PGA (GS=0.35; PD=0.39) and PGA+CRP (GS=0.44; PD=0.46) were weak to moderate. ThermoDAI and ThermoDAI-CRP also showed strong correlations with Clinical Disease Activity Index (ρ>0.83), Simplified Disease Activity Index (ρ>0.85) and Disease Activity Score with 28-Joint Counts-CRP (ρ>0.81) and high sensitivity for detecting active synovitis using remission criteria. CONCLUSIONS: ThermoDAI and ThermoDAI-CRP showed stronger correlations with ultrasound-determined synovitis than PGA and PGA + CRP, thus presenting an opportunity to improve remote consultations with patients with RA.

Assessment of inflammation in patients with rheumatoid arthritis using thermography and machine learning: a fast and automated technique.

OBJECTIVES: Sensitive detection of joint inflammation in rheumatoid arthritis (RA) is crucial to the success of the treat-to-target strategy. In this study, we characterise a novel machine learning-based computational method to automatically assess joint inflammation in RA using thermography of the hands, a fast and non-invasive imaging technique. METHODS: We recruited 595 patients with arthritis and osteoarthritis, as well as healthy subjects at two hospitals over 4 years. Machine learning was used to assess joint inflammation from the thermal images of the hands using ultrasound as the reference standard, obtaining a Thermographic Joint Inflammation Score (ThermoJIS). The machine learning model was trained and tuned using data from 449 participants with different types of arthritis, osteoarthritis or without rheumatic disease (development set). The performance of the method was evaluated based on 146 patients with RA (validation set) using Spearman's rank correlation coefficient, area under the receiver-operating curve (AUROC), average precision, sensitivity, specificity, positive and negative predictive value and F1-score. RESULTS: ThermoJIS correlated moderately with ultrasound scores (grey-scale synovial hypertrophy=0.49, p<0.001; and power Doppler=0.51, p<0.001). The AUROC for ThermoJIS for detecting active synovitis was 0.78 (95% CI, 0.71 to 0.86; p<0.001). In patients with RA in clinical remission, ThermoJIS values were significantly higher when active synovitis was detected by ultrasound. CONCLUSIONS: ThermoJIS was able to detect joint inflammation in patients with RA, even in those in clinical remission. These results open an opportunity to develop new tools for routine detection of joint inflammation.

MR imaging of early rheumatoid arthritis.

Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with early rheumatoid arthritis. However, diagnosis is somewhat difficult in the early stages of the disease because the diagnostic criteria were developed from data obtained in patients with established rheumatoid arthritis and therefore are not readily applicable. Magnetic resonance (MR) imaging is increasingly being used in the assessment of rheumatoid arthritis due to its capacity to help identify the key pathologic features of this disease entity at presentation. MR imaging has demonstrated greater sensitivity for the detection of synovitis and erosions than either clinical examination or conventional radiography and can help establish an early diagnosis of rheumatoid arthritis. It also allows the detection of bone marrow edema, which is thought to be a precursor for the development of erosions in early rheumatoid arthritis as well as a marker of active inflammation. In addition, MR imaging can help differentiate rheumatoid arthritis from some clinical subsets of peripheral spondyloarthropathies by allowing identification of inflammation at the insertions of ligaments and tendons (enthesitis).

Imaging of skull vault tumors in adults.

The skull vault, formed by the flat bones of the skull, has a limited spectrum of disease that lies between the fields of neuro- and musculoskeletal radiology. Its unique abnormalities, as well as other ubiquitous ones, present particular features in this location. Moreover, some benign entities in this region may mimic malignancy if analyzed using classical bone-tumor criteria, and proper patient management requires being familiar with these presentations. This article is structured as a practical review offering a systematic diagnostic approach to focal calvarial lesions, broadly organized into four categories: (1) pseudolesions: arachnoid granulations, meningo-/encephaloceles, vascular canals, frontal hyperostosis, parietal thinning, parietal foramina, and sinus pericrani; (2) lytic: fibrous dysplasia, epidermal inclusion and dermoid cysts, eosinophilic granuloma, hemangioma, aneurysmal bone cyst, giant cell tumor, metastasis, and myeloma; (3) sclerotic: osteomas, osteosarcoma, and metastasis; (4) transdiploic: meningioma, hemangiopericytoma, lymphoma, and metastasis, along with other less common entities. Tips on the potential usefulness of functional imaging techniques such as MR dynamic susceptibility (T2*) perfusion, MR spectroscopy, diffusion-weighted imaging, and PET imaging are provided.

Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival.

Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy.

Role of the galanin N-terminal fragment (1-15) in anhedonia: Involvement of the dopaminergic mesolimbic system.

BACKGROUND: Anhedonia is a core feature of depressive disorders. The galanin N-terminal fragment (1-15) plays a role in mood regulation since it induces depression and anxiogenic-like effects in rats. In this study, we analysed galanin N-terminal fragment (1-15) actions in anhedonic-like behaviours in rats using operant and non-operant tests and the areas involved with these effects. METHODS: Galanin N-terminal fragment (1-15) effects were analysed in saccharin self-administration, sucrose preference, novelty-suppressed feeding and female urine sniffing tests. The areas involved in galanin N-terminal fragment (1-15)-mediated effects were studied with positron emission tomography for in vivo imaging, and we analysed the ventral tegmental area and nucleus accumbens. Galanin N-terminal fragment (1-15) had effects on the mRNA expression of the dopamine transporters Dat and Vmat2; the C-Fos gene; the dopamine receptors D1, D2, D3, D5; and the galanin receptors 1 and 2. RESULTS: Galanin N-terminal fragment (1-15) at a concentration of 3 nmol induced a strong anhedonia-like phenotype in all tests. The involvement of galanin receptor 2 was demonstrated with the galanin receptor 2 antagonist M871 (3 nmol). The 18F-fluorodeoxyglucose positron emission tomography images indicated the action of galanin N-terminal fragment (1-15) over several nuclei of the limbic system. Galanin N-terminal fragment (1-15)-mediated effects also involved changes in the expression of Dat, Vmat2, D3 and galanin receptors in the ventral tegmental area as well as the expression of C-Fos, D1, D2 and D3 and TH immunoreactivity in the nucleus accumbens. CONCLUSIONS: Our results indicated that galanin N-terminal fragment (1-15) exerts strong anhedonic-like effects and that this effect was accompanied by changes in the dopaminergic mesolimbic system. These results may provide a basis for the development of novel therapeutic strategies using galanin N-terminal fragment (1-15) analogues for the treatment of depression and reward-related diseases.

Long-term clinical and radiological magnetic resonance imaging outcome of abscess-associated spontaneous pyogenic vertebral osteomyelitis under conservative management.

OBJECTIVES: Management of abscess-associated spontaneous pyogenic vertebral osteomyelitis (PVO) is controversial. The role of magnetic resonance imaging (MRI) in follow-up and its relation with clinical outcome is often unclear. This study evaluates the clinical and MRI outcome of abscess-associated PVO under conservative treatment. METHODS: Prospective study and retrospective review of patients with spontaneous PVO in whom the initial MRI showed soft-tissue involvement (STI). Treatment according to a medical protocol, clinical and MRI follow-up at diagnosis, and at 2 later time points: early response (ER, at the end of antibiotic therapy) and late response (LR, >or=6 months after therapy). MRI classified STI as soft-tissue edema (STE) or abscess. RESULTS: Of the 27 patients (20 men, 74%, age 65+/-14), all had pain, 17 (63%) had fever, and 6 (22%) had mild neurological impairment. The main etiology was Staphylococcus sp (11, 41%). Twenty-one (81%) had bacteremia and 18 (67%) had epidural/paraspinal abscess. Patients received antibiotics for 9 weeks, administered orally for 6 weeks. ER: Three cases failed and general improvement was seen in the remainder. MRI showed persistent STI, which diminished in all cases except 1, whereas bone/disc findings remained. LR: All patients were cured; 8 reported mild sequelae (30%). MRI still revealed bone/disc abnormalities, but residual STE was infrequent. Median follow-up was 29 months. CONCLUSION: Most patients with abscess-associated spontaneous PVO are cured with a conservative approach. MRI shows STI reduction at ER evaluation. Repeat MRI is probably unnecessary if clinical and laboratory outcomes are satisfactory. The persistence of bone/disc MRI findings alone does not represent therapeutic failure.

Spontaneous pyogenic facet joint infection.

OBJECTIVE: To analyze the clinical features, approaches to management, and outcome of spontaneous pyogenic facet joint infection (PFJI) in adults. PATIENTS AND METHODS: Case series of 10 adults with microbiologically proven PFJI diagnosed during a 10-year period in a teaching hospital, plus a review of 32 additional cases previously reported (PubMed 1972 to 2003). Patients with prior spinal instrumentation or surgery and injection drug users were excluded. Only cases that were sufficiently detailed to be individually analyzed were included. These 32 cases, together with our 10 patients, form the basis of the present analysis. RESULTS: PFJI represented nearly 20% of all spontaneous pyogenic spinal infection diagnosed in our hospital during a 10-year period. This data suggest that PFJI is more common than was previously thought. Of the 42 patients with PFJI, 26 (62%) were men and 16 (38%) were women, with ages ranging from 20 to 86 years (mean age, 59+/-15 years); 55% of patients were older than 60 years. The most common location of infections was the lumbosacral region (86%). All patients presented with severe back pain; fever was noted in 83% of the cases and neurological impairment in nearly 48%. In 38% of patients a systemic predisposing factor for infection was present; the most common conditions were diabetes mellitus, malignancies, and alcoholism. In almost 36% of cases, one or more concomitant infectious processes due to the same microorganism was found, mainly arthritis, skin and soft-tissue infections, endocarditis, and urinary tract infections. Staphylococcus aureus was the most common etiologic microorganism (86% of cases). Bacteremia was documented in 81% of the cases. The diagnosis of PFJI was based mainly on imaging study findings. Paraspinal and/or epidural extension was frequent (81% of cases), but its presence did not indicate a worse prognosis. Medical treatment alone was usually successful. The overall prognosis of PFJI was good, with a mortality rate of only 2%. The great majority of patients were cured without functional sequelae. CONCLUSION: Incidence data from our institution reveal that PFJI is not a rare condition, representing approximately 20% of all pyogenic spinal infections. This entity should be considered in the differential diagnosis of patients with low back pain, especially in the presence of fever, whatever the patient's immunological status.

Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS).

Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data.

Intracisternal galanin/angiotensin II interactions in central cardiovascular control.

The aim of this work was to investigate the interactions between angiotensin II (Ang II) and galanin(1-29) [GAL(1-29)] or its N-terminal fragment galanin(1-15) [GAL(1-15)] on central cardiovascular control. The involvement of angiotensin type1 (AT1) receptor subtype was analyzed by the AT1 antagonist, DuP 753. Anesthesized male Sprague-Dawley rats received intracisternal microinjections of Ang II (3 nmol) with GAL(1-29) (3 nmol) or GAL(1-15) (0.1 nmol) alone or in combination. The changes in mean arterial pressure (MAP) and heart rate (HR) recorded from the femoral artery were analyzed. The injection of Ang II and GAL(1-15) alone did not produce any change in MAP. However, coinjections of both Ang II and GAL(1-15) elicited a significant vasopressor response. This response was blocked by DuP 753. Ang II and GAL(1-15) alone produced an increase in HR. The coinjections of Ang II with GAL(1-15) induced an increase in HR not significantly different from the tachycardia produced by each peptide. The presence of DuP 753 counteracted this response. GAL(1-29) alone elicited a transient vasopressor response that disappeared in the presence of Ang II. The coinjections of Ang II with GAL(1-29) and with DuP 753 restored the transient vasopressor effect produced by GAL(1-29). GAL(1-29) produced a slight but significant tachycardic effect that was not modified in the presence of Ang II. The presence of DuP 753 did not modify the tachycardic response produced by Ang II and GAL(1-29). These results give indications for the existence of a differential modulatory effect of Ang II with GAL(1-15) and GAL(1-29) on central blood pressure response that might be dependent on the activity of the angiotensin AT1 receptor subtype.

Acquired hypophosphatemic osteomalacia associated with multiple myeloma.

Hypophosphatemic osteomalacia is a rare but important complication of multiple myeloma. In these cases, the pathophysiology of the phosphate renal wasting notably differs from oncogenic osteomalacia and is due to light-chain nephropathy, resulting in proximal tubular dysfunction which is not restricted to phosphate handling. These patients seems to have a distinct type of plasma cell disorder characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. For this reason hypophosphatemic osteomalacia is the presenting feature that leads to the diagnosis of multiple myeloma in most of these patients. Recognition of this complication is important, since supportive treatment with phosphate supplements and calcitriol may substantially alleviate pain and weakness associated with hypophosphatemia.

Propranolol blocks the tachycardia induced by galanin (1-15) but not by galanin (1-29).

The efferent pathways involved in the tachycardia induced by intracisternal injections of the N-terminal galanin fragment (1-15) (GAL (1-15)) and galanin (GAL (1-29)) has been evaluated in rats pretreated with the cholinergic antagonist atropine or the beta-antagonist propranolol. The pretreatment with propranolol significantly blocked the tachycardic and vasopressor effect produced by intracisternal injection of GAL (1-15) (p<0.05), but the pretreatment with atropine did not modify these cardiovascular effects. However, the cardiovascular response elicited by GAL (1-29) is modified by the pretreatment with atropine (p<0.05) but not by propranolol. These findings demonstrate that the central cardiovascular action of GAL (1-15), but not GAL (1-29), is mediated by beta-receptor stimulation and this suggests the existence of a different pathway involved in the cardiovascular response produced by the N-terminal galanin fragment as compared with the parent molecule GAL (1-29).

Angiotensin II modulates the cardiovascular responses to microinjection of NPY Y1 and NPY Y2 receptor agonists into the nucleus tractus solitarii of the rat.

The aim of this work was to investigate the modulation of the cardiovascular effects of neuropeptide Y (NPY) in the nucleus tractus solitarii (NTS) by angiotensin II (Ang II) and to determine the NPY receptor subtype involved in this modulation. Anesthesized Sprague-Dawley rats received microinjections in the NTS of Ang II (threshold and ED(50) doses) with NPY Y(1) agonist Leu(31)Pro(34)NPY and NPY Y(2) agonist NPY(13-36) (threshold and ED(50) doses). The changes in mean arterial pressure (MAP) and heart rate (HR) recorded in the femoral artery were analyzed during 60 min after the microinjections. The injection of threshold doses of Ang II, Y(1) agonist or Y(2) agonist alone did not produce any change in cardiovascular parameters. However, the co-injections into the NTS of threshold doses of both Ang II and the Y(1) agonist elicited significant increases of MAP and HR of about 12 and 10%, respectively. The co-administration of threshold doses of Ang II with the Y(2) agonist also induced a significant vasopressor response. The vasodepressor and bradycardiac effect of an ED(50) dose of the Y(1) agonist was significantly counteracted (P<0.01) by a threshold dose of Ang II. The vasopressor effect elicited by an ED(50) dose of the Y(2) agonist was significantly enhanced by a threshold dose of Ang II (P<0.01). No significant change of cardiovascular responses elicited by an ED(50) dose of Ang II was observed in the presence of threshold doses of the Y(1) agonist or of the Y(2) agonist. The present study gives functional evidences for a differential modulatory activity of Ang II on the cardiovascular responses mediated by Y(1) and Y(2) receptor subtypes, which may be of relevance for central cardiovascular regulation in the NTS.

MRI of sports-related injuries of the foot and ankle: part 1.

The ankle is one of the most frequently injured joints in the course of sports activities. MR imaging has become the modality of choice in the evaluation of most of these lesions, especially in competitive athletes. The purpose of this article is: (1) To illustrate the MR imaging features of a great number of sports-related injuries of the ankle, correlating it with lesional mechanisms and clinical findings, and (2) To review the role of MR imaging in clinical management and surgical planning of these injuries, especially in competitive athletes. In order to a better understanding of these lesions, a classification based on the anatomic origin are outlined. The spectrum of injuries has been classified in: (1) osseous lesions, (2) ligamentous injuries, (3) tendinous lesions, (4) impingement impingement, and (5) plantar fascial lesions.

Galanin receptor/neuropeptide y receptor interactions in the central nervous system.

The presence of Galanin and Neuropeptide Y and/or their receptors in several areas of the brain involved in memory, mood, cardiovascular control and food intake indicates that Galanin, and Neuropeptide Y could equilibrate the physiological actions of each other. There is evidence for the existence of interactions between Galanin Receptor and Neuropeptide Y Receptor in the nucleus of the solitarii tract (NTS), hypothalamus and dorsal raphe nucleus probably taking place with the formation of heteromers between Galanin Receptor and Neuropeptide Y Y1 Receptor. The galanin fragment (Gal 1-15) preferring receptors may instead be formed by the GalR1-GalR2 heteromer which in the NTS may interact with Neuropeptide Y Y2 receptors. These receptor heteromers may be one key molecular mechanism for Galanin and its N-terminal fragment (Galanin 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional, metabolic and cardiovascular networks.

On the existence and function of galanin receptor heteromers in the central nervous system.

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.

Changing trends in the epidemiology of pyogenic vertebral osteomyelitis: the impact of cases with no microbiologic diagnosis.

OBJECTIVES: The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined. METHODS: Retrospective analysis of all cases of vertebral osteomyelitis in our center (1991-2009) and retrospective analysis of cases of PVO (2005-2009). Clinical data, diagnostic procedures, treatment, and outcome were reviewed. A comparative analysis between microbiologically confirmed PVO (MCPVO) and probable PVO (PPVO) was performed. RESULTS: Increasing incidence of PVO (+0.047 episodes/100,000 inhabitants-year). During the last decade, there was an increase of PPVO (+0.059 episodes/100,000 inhabitants-year) with stable incidence of MCPVO. During 2005-2009, there were 72 patients [47 (65%) MCPVO and 25 (35%) PPVO]. 60% men; mean age was 66 years. Bacteremia was found in 59%. Computed tomographic guided vertebral biopsy, positive in 7/36 (19%), was more successful among patients with bacteremia. Among MCPVO, there was an increasing proportion of less virulent bacteria. Cases of MCPVO presented more frequently with sepsis, fever, and high acute-phase reactants, and PPVO cases were mostly treated with oral fluoroquinolones plus rifampin. No differences were found between both groups in outcome (93% success, 22% sequelae). CONCLUSIONS: An epidemiologic change of PVO is suggested by a higher incidence of PPVO and the isolation of less virulent microorganisms among MCPVO. In this setting, the availability of an oral and effective empirical antibiotic therapy may challenge an exhaustive prosecution of the etiology.