Which comes first: the antigen or the adjuvant?

Recent attempts to develop an HIV-1 vaccine indicate that viral replication can be limited by the induction of viral-specific T cell responses; however, recent trials of vaccine candidates designed to target CD8⁺ T cell responses were unsuccessful. In this issue, Sui and colleagues used a nonhuman primate model to investigate the effect of various vaccine adjuvants on the efficacy of SIV immunization. Unexpectedly, Sui et al. discovered that animals given adjuvant alone in the absence of SIV antigen exhibited a pronounced decrease in viral load following viral challenge. Vaccination with viral antigens combined with adjuvant correlated with the expansion of a population of cells with similarity to myeloid-derived suppressor cells (MDSCs) that may have suppressed vaccine-elicited T cell responses. Together, these results suggest that both innate and adaptive vaccine-elicited immune responses will need to be considered in future HIV-1 vaccine development.The HIV-1 vaccine field has debated the importance of eliciting strong functional antibody responses to prevent viral invasion of target cells versus eliciting potent T cell responses to kill virus-infected cells. This debate has converged on the consensus that both arms of the immune response will likely be necessary to achieve effective HIV-1 vaccination (1, 2). Additionally, the field has turned toward investigating TLR agonists and other adjuvants to enhance dendritic cell antigen presentation and augment vaccine-elicited responses (3–8). Despite repeated attempts to produce an efficacious HIV-1 vaccine, our knowledge of the adjuvant-specific impact on both the humoral and cellular arms of vaccine-elicited immune responses is still nascent. Moreover, the necessity of HIV-1 vaccine candidates to engage the innate immune system is an ongoing area of investigation (9, 10).     

Migraine and Autonomic Dysfunction: Which Is the Horse and Which Is the Jockey?

Purpose of Review

Symptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.

Recent Findings

Several studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment.

Summary

Three trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.

     

Which heparin during the investigation of chest pain at term pregnancy?

A patient was treated with a therapeutic dose of low-molecular-weight heparin, then required caesarean section immediately following its administration. Reasons for preferring this heparin over unfractionated heparin are acknowledged but not supported for short-term use in an obstetric patient near term.     

Abuse history: is it really important in the medical encounter?

The negative effects of a history of severe abuse as a child are becoming increasingly well known to the physician and, in the adult survivor, include both mental health and physical sequelae. Intervention for emotional and psychologic consequences can include a mental health referral. Awareness of physical sequelae can aid the physician in diagnosis and intervention. However, the impact of severe childhood abuse in the medical encounter does not end with diagnosing and managing somatic complaints and/or providing a mental health referral. Severe childhood abuse directly affects the physician-patient relationship by causing the predictable difficulties that adult survivors of severe abuse experience in any of their intimate relationships.     

The European Union: open to the practising physician?

The European Union (EU) has powers and responsibilities in the area of public health, while the organisation of healthcare facilities remains the concern of member states. However, a series of directives has, since the late 1970s, sought to ensure the right of individual practitioners to travel freely throughout the EU, both to obtain specialist training and to practise in all member states on the same basis as doctors working in the member states where they were first registered. More recently, there has been mutual recognition of completion of specialist training across the EU. A new directive concerning the mobility of medical practitioners across the EU is under discussion.     

Drug development for severe asthma: what are the metrics?

Although reversible airway obstruction in part defines asthma, lung function as measured by spirometry alone inadequately predicts the value of new therapeutic agents in the treatment of severe asthma. Our objectives are 1) to review whether pulmonary function and bronchodilator reversibility are endpoints for drug discovery and 2) to identify parameters that predict efficacy in drug development in severe asthma. An English language literature search using MedLine and PubMed was conducted from 1997 to present concerning pathophysiology, diagnosis and therapy of severe asthma using the terms "severe asthma," "irreversible asthma," "difficult asthma," "airway remodeling," "fixed airway obstruction," "reversibility" and "bronchodilator reversibility" as index terms. Eight studies were characterized that encompass 1424 subjects with asthma. Our review identified the limitations of using bronchodilator reversibility as a predictor in drug development for severe asthma. Neither improvement in lung function nor bronchodilator reversibility characterized the benefit of new drugs in the treatment of severe asthma. Newly approved drugs in the treatment of severe asthma show decreased asthma exacerbations and improved quality of life associated with steroid-sparing benefits without altering bronchodilator responsiveness or improving lung function. Although changes in lung function predict asthma control in mild/moderate asthma, lung function alone is inadequate to assess improvement in asthma control in severe asthma manifested by fixed airway obstruction. Endpoints that focus on asthma control, as defined by the Expert Panel Report 3 and GINA guidelines, may predict the value of new therapeutics in the management of severe asthma.     

Monitoring carbon dioxide in critical care: the newest vital sign?

Carbon dioxide (CO(2)) monitoring can yield substantial information about cardiac and pulmonary function. Because capnography is not complicated, it is relatively easy to apply in a wide variety of clinical settings. A new area of CO(2) measurement is sublingual CO(2). Although outcomes data are as yet unavailable for this technology, its ease of use makes it an attractive monitoring tool to assess severity of illness and predict patients' responses to therapy. This article describes the pathophysiology and clinical applications of the technologies and describes why they may well be "the newest vital signs."     

Room at the top?

Nurse executives have joined hospital administrative teams, but are they accepted as fully integrated team executives? Learn how nurse executives and their influential colleagues view integration and its influences.     

Domestic Abuse in the Emergency Department: Can a Risk Profile Be Defined?

OBJECTIVES: The main purpose of this study was to determine whether any clinical or demographic characteristics could identify adult female patients presenting to the emergency department (ED) with a history of domestic abuse. A second objective was to describe the frequency, types, and severity of this abuse. METHODS: This study was a crosssectional survey of 611 women conducted in an academically-affiliated, urban ED. Domestic abuse was described as "recent" (within the preceding 12 months) or "lifetime" (recent or past). This included emotional, physical, and sexual abuse. RESULTS: Recent (7.9%, n = 48) and lifetime (38%, n = 232) domestic abuse was reported. For recently abused women, violence had been severe (87.5%, n = 42) and was associated with 1) trauma (OR 5.4, 95% CI = 2.6 to 11.6), 2) obstetrical and gynecological syndromes (OR 5.6, 95% CI = 2.4 to 13.2), and 3) psychiatric symptoms and substance use (OR 7.3, 95% CI = 2.4 to 22.0). The sensitivities and positive predictive values of these risk factors individually (<27.1% and <25.0%, respectively) and in aggregate (56.3% and 20.9%, respectively) were low. These indicators predicted only 27 (56.3%) of recently abused women. Lifetime domestic violence was more likely in homeless women (OR 5.8, 95% CI = 2.2 to 15.0), although less likely in immigrants (OR 0.4, 95% CI = 0.3 to 0.7). CONCLUSIONS: Clinical presentations and demographic characteristics of women presenting to the ED may not be sensitive or predictive indicators of domestic abuse. In the absence of typical clinical or demographic findings, asking all women in the ED about domestic abuse remains a necessary priority.     

Drug disease: is it iatrogeny?

AIM: To draw attention of medical professionals to the problem of side effects of medication. MATERIAL AND METHODS: Analysis of evolution of views on unwanted effects of the drugs. RESULTS: The authors hold that the problem of side effects of many drugs is underestimated in Russia as relevant information is scare. CONCLUSION: Detection of side effects of the drugs allows conduction of prophylactic measures.     

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.