Enhanced negative feedback sensitivity of the hypothalamus–pituitary–adrenal axis in chronic myogenous facial pain⋆

Dysregulations of the hypothalamus–pituitary–adrenal (HPA) axis, as a physiological substrate of stress, have been observed in patients with different stress‐related and chronic pain disorders. In this study, we investigated possible dysregulations of the HPA axis in patients with masticatory muscles pain. In 20 patients with myogenous facial pain and 20 healthy controls, awakening cortisol responses, i.e. cortisol rise in the first hour after awakening, as well as a short circadian free cortisol profile, i.e. four cortisol samples over 12h during the day, were assessed before and after administration of 0.5mg dexamethasone. Results: In comparison to controls, chronic myogenous facial pain patients showed enhanced and prolonged suppression of cortisol after the administration of 0.5mg dexamethasone. Unstimulated cortisol response (before dexamethasone‐intake) to awakening and cortisol levels during the day did not differ between the groups. Dysregulation in terms of enhanced negative feedback suppression exists in chronic myogenous facial pain. These results are in line with a multifactorial etiology of chronic facial pain, shifting the perspective away from a local towards a more central etiology with dysregulations in the stress and pain modulating system.     

A prospective multi-centre study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin

Purpose Since ¹⁸F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated inflammatory cells, positron emission tomography (PET) with FDG could be valuable in diagnosing patients with fever of unknown origin (FUO). The aim of this study was to validate the use of FDG-PET as part of a structured diagnostic protocol in the general patient population with FUO. Methods From December 2003 to July 2005, 70 patients with FUO were recruited from one university hospital (n=38) and five community hospitals (n=32). A structured diagnostic protocol including FDG-PET was used. A dedicated, full-ring PET scanner was used for data acquisition. FDG-PET scans were interpreted by two staff members of the department of nuclear medicine without further clinical information. The final clinical diagnosis was used for comparison with the FDG-PET results. Results Of all scans, 33% were clinically helpful. The contribution of FDG-PET to the final diagnosis did not differ significantly between patients diagnosed in the university hospital and patients diagnosed in the community hospitals. FDG-PET contributed significantly more often to the final diagnosis in patients with continuous fever than in patients with periodic fever. FDG-PET was not helpful in any of the patients with normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Conclusion FDG-PET is a valuable imaging technique as part of a diagnostic protocol in the general patient population with FUO and a raised ESR or CRP.     

Chemokine receptor expression in HIV-positive persons with oropharyngeal candidiasis

OBJECTIVE: In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated with the accumulation of CD8+ T cells at the epithelial/lamina propria interface within the lesion together with increased tissue-associated cytokines and chemokines. Despite this reactivity, a dysfunction in the ability of the CD8+ cells to reach the organism at the outer epithelium is postulated. The purpose of this study was to examine chemokine receptors present in the OPC lesions for a potential role in susceptibility to infection. METHODS: Biopsies taken from buccal mucosa of HIV- persons, healthy mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein immunohistochemical staining or RNA analysis by real-time PCR and Superarray. RESULTS: There was little change in expression of chemokine receptors at the protein or RNA level between OPC+ and OPC- tissue. At the protein level, increases occurred in OPC+ persons only if associated with CD8 cells. In the Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC- and HIV+ OPC+ tissue. CONCLUSION: Tissue-associated chemokine receptor expression does not appear to contribute to the dysfunction in cellular migration associated with susceptibility to OPC.     

Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.     

Characterization of the immune status of CD8+ T cells in oral lesions of human immunodeficiency virus-infected persons with oropharyngeal Candidiasis

Oropharyngeal candidiasis (OPC) remains the most common oral infection in human immunodeficiency virus (HIV) disease. In a high percentage of HIV(+) persons with reduced CD4(+) T cells, oral lesions with Candida present at the outer epithelium have an accumulation of CD8(+) T cells at the epithelium-lamina propria interface associated with reduced expression of the mucosal cell-trafficking adhesion molecule E-cadherin. The purpose of the present study was to characterize the immune status of these CD8(+) T cells. Immunohistochemical staining for phenotypic and activation and costimulation markers was performed on frozen biopsy tissue sections from HIV(+) OPC(+) persons with accumulated CD8(+) T cells. CD8(+) T cells consisted primarily of central memory cells by virtue of positive CD45RO (memory) and CD27 (central memory) expression. However, concomitant negative expression of CD62L and CCR7 (effector memory) was suggestive of a transitioning memory phenotype within the tissue. Despite this, the cells are considered to be activated on the basis of positive expression of CD69. The CD8(+) T cells are not considered to be NK T cells or anti-HIV CD8(+) T cells because of negative or low expression of CD161 and vascular cell adhesion molecule, respectively. These results suggest that the accumulated mucosal migratory-challenged CD8(+) T cells are otherwise normal memory T cells in an activated state.     

A comparison of the diagnostic value of MRI and <Superscript>18</Superscript>F-FDG-PET/CT in suspected spondylodiscitis

Purpose

The purpose of this study was to evaluate the diagnostic value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT scan) and magnetic resonance imaging (MRI) in diagnosing spondylodiscitis and its complications, such as epidural and paraspinal abscesses.

Methods

From January 2006 to August 2013 patients with a clinical suspicion of spondylodiscitis, with an infection, or with fever of unknown origin were retrospectively included if ¹⁸F-FDG-PET/CT and MRI of the spine were performed within a 2-week time span. Imaging results were compared to the final clinical diagnosis and follow-up data were collected.

Results

Sixty-eight patients were included of whom 49 patients were diagnosed with spondylodiscitis. MRI showed an overall sensitivity of 67 % and specificity of 84 %. Diagnostic accuracy was 58 %, when MRI was performed within 2 weeks after the start of symptoms and improved to 82 %, when performed more than 2 weeks after onset of symptoms. ¹⁸F-FDG-PET/CT showed a sensitivity of 96 % and a specificity of 95 %, with no relation to the interval between the scan and the start of symptoms.

Conclusions

As compared to MRI, ¹⁸F-FDG-PET/CT has superior diagnostic value for detecting early spondylodiscitis. After 2 weeks both techniques perform similarly.

     

Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine,but not irradiated sporozoites,in mice

Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P = 0.0002), and IgG3 (P = 0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.     

Mortality and business cycles by level of development: evidence from Mexico

We investigate the relationship between mortality and business cycles within Mexico, where development varies significantly. We exploit this variation by separately analyzing the top ten and bottom ten developed states for the period 1993-2004. We find that while overall mortality is procyclical nationally and in the top ten states, it is countercyclical in the bottom ten. Further, we show that in the top ten states mortality due to non communicable conditions is procyclical, while in the bottom ten mortality due to non communicable conditions and infectious and parasitic diseases are countercyclical. Our results suggest that the relationship between mortality and business cycles may vary by level of development.     

A survey of emergency medical services in mountain areas of Europe and North America: official recommendations of the International Commission for Mountain Emergency Medicine (ICAR Medcom)

Survey of on-site treatment of patients in mountain areas of 14 countries in Europe and North America (nonresponder rate 33%) to compare emergency medical services. Around 37,535 ground rescuers and 747 helicopters are ready for evacuation of casualties and patients in mountain areas. And 1316 physicians and 50,967 paramedics take part in ground and air mountain rescue operations. In Europe, 63.2% of helicopters have a physician on board, 17.8% are staffed with a paramedic, and 19% have no medically trained personnel on board. In North America, 31.6% (p < 0.001) of helicopters are staffed with a doctor, 59.3% (p < 0.001) with a paramedic, and 9.1% (p < 0.001) have no medical personnel. The percentage of on-site treatment according to the recommendations of the International Liaison Committee on Resuscitation (ILCOR) or International Commission for Alpine Rescue (ICAR) varies among all countries (p < 0.001) and is positively related to the percentage of physician-staffed helicopters (r = 0.76, p < 0.001). Paramedics in 90.9% countries are obliged to be medically trained, but physicians only need to have a standardized training in emergency medicine in 50% (p < 0.042). On-site treatment according to ILCOR or ICAR recommendations is performed more often in countries where physicians are regularly involved in mountain rescue operations. However, no conclusions can be drawn from the data as to the efficiency of treatment. The data show a lack of medical education in specific, mountain rescue-related problems. Physicians involved should undergo suitable training.