Heather J. Duncan

The Diagnosis of a Conductive Olfactory Loss

Objectives/Hypothesis Two of the most common causes of olfactory loss include upper respiratory infection (URI) and nasal or sinus disease. The etiology of most URI‐related losses is thought to be viral and, as yet, there is no available treatment. In contrast, nasal or sinus disease produces an obstructive or conductive loss that often responds dramatically to appropriate therapy. Therefore, the distinction is important but in many cases may be difficult because such patients often present with no other nasal symptoms, and routine physical findings may be nonspecific. The purpose of this report is to characterize those aspects of the history and physical examination that will help to substantiate the diagnosis of a conductive olfactory loss.

Hemodialysis Vascular Access Dysfunction: From Pathophysiology to Novel Therapies

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over USD 1 billion per annum. Most hemodialysis grafts fail due to a venous stenosis (venous neointimal hyperplasia) which then results in thrombosis of the graft. Despite the magnitude of the clinical problem there are currently no effective therapies for this condition. The current review (a) describes the pathogenesis and pathology of venous stenosis in dialysis access grafts and (b) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. Special emphasis is laid on the fact that PTFE dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia.

Altered Dynamics of Kv1.3 Channel Compartmentalization in the Immunological Synapse in Systemic Lupus Erythematosus

Aberrant T cell responses during T cell activation and immunological synapse (IS) formation have been described in systemic lupus erythematosus (SLE). Kv1.3 potassium channels are expressed in T cells where they compartmentalize at the IS and play a key role in T cell activation by modulating Ca2+ influx. Although Kv1.3 channels have such an important role in T cell function, their potential involvement in the etiology and progression of SLE remains unknown. This study compares the K channel phenotype and the dynamics of Kv1.3 compartmentalization in the IS of normal and SLE human T cells. IS formation was induced by 1–30 min exposure to either anti-CD3/CD28 Ab-coated beads or EBV-infected B cells. We found that although the level of Kv1.3 channel expression and their activity in SLE T cells is similar to normal resting T cells, the kinetics of Kv1.3 compartmentalization in the IS are markedly different. In healthy resting T cells, Kv1.3 channels are progressively recruited and maintained in the IS for at least 30 min from synapse formation. In contrast, SLE, but not rheumatoid arthritis, T cells show faster kinetics with maximum Kv1.3 recruitment at 1 min and movement out of the IS by 15 min after activation. These kinetics resemble preactivated healthy T cells, but the K channel phenotype of SLE T cells is identical to resting T cells, where Kv1.3 constitutes the dominant K conductance. The defective temporal and spatial Kv1.3 distribution that we observed may contribute to the abnormal functions of SLE T cells.

Identification of Obstructive Sleep Apnea in Patients Who Snore

As the field of sleep medicine has evolved, the clinical implications of obstructive sleep apnea (OSA) in snoring patients have become well accepted. Recent advances in surgical therapy for snoring allow otolaryngologists to offer simple outpatient treatment to patients with this problem. However, because the incidence of OSA in snorers seeking medical attention is unknown, the appropriate pretreatment evaluation of these patients is a subject of continued debate. Ninety‐four snoring patients were recruited for a study to determine the incidence of OSA in this highly selected population. Subjects answered an extensive sleep questionnaire to determine factors that might suggest a diagnosis of OSA. Level III ambulatory sleep studies were performed on each participant. The incidence of OSA in this group was 72% (42% severe and 30% mild to moderate). Twenty of the subjects with OSA also underwent formal level I sleep studies, and the diagnosis of OSA was confirmed in each instance. Although there was a relationship between body mass index and OSA and certain questions correlated with OSA, the sensitivity and specificity of these data alone or in combination were too low to recommend their use in lieu of a formal sleep study. Given the remarkably high incidence of OSA in this group, which may reflect that seen by otolaryngologists who treat snoring, a sleep study should be performed to diagnose OSA and institute therapy for this condition. Level III ambulatory monitoring devices may be the most cos‐teffective alternative for evaluating this high‐risk population.

Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) T cells exhibit several activation signaling anomalies including defective Ca(2+) response and increased NF-AT nuclear translocation. The duration of the Ca(2+) signal is critical in the activation of specific transcription factors and a sustained Ca(2+) response activates NF-AT. Yet, the distribution of Ca(2+) responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca(2+) alterations are not fully understood. Kv1.3 channels control Ca(2+) homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca(2+) defect. The present study compares single T cell quantitative Ca(2+) responses upon formation of the IS in SLE, normal, and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca(2+) concentrations and Kv1.3 trafficking in the IS by two-photon microscopy. We found that sustained [Ca(2+)](i) elevations constitute the predominant response to antigen stimulation of SLE T cells. This defect is selective to SLE as it was not observed in RA T cells. Further, we observed that in normal T cells termination of Ca(2+) influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca(2+) responses in SLE T cells. Thus, we propose that Kv1.3 trafficking abnormalities contribute to the altered distribution in Ca(2+) signaling in SLE T cells. Overall these defects may explain in part the T cell hyperactivity and dysfunction documented in SLE patients.

Alternative Medicine Use in Dialysis Patients: Potential for Good and Bad!

Although alternative medicines are widely used within the general population, the extent of their use within the dialysis population is unknown. It is possible that dialysis patients may be more likely to turn towards alternative therapies in view of the chronicity of their disease. In addition, this particular patient population could be at an increased risk of toxicity from these therapies due to an absence of renal excretion. A detailed assessment of complementary and alternative medicine use in our dialysis patients revealed that 18% of our patients had used or were using some form of alternative medicine therapy.An additional 63% of our patients, however, were willing to use a complementary or alternative medication. Our results suggest that hemodialysis patients are extremely receptive to the use of such therapies and are therefore exposed to all their potential benefit and harm.

Primary Olfactory Disorders: Anosmia, Hyposmia, and Dysosmia

It has been estimated that at least 2 million Americans suffer from a disorder of taste or smell,1 but this is probably an underestimation, particularly if one considers the significant degree of smell impairment in the elderly population. Although there are over 200,000 visits to physicians each year for chemosensory disorders, many more of these problems go unreported; they tend to be dismissed by patients as well as by physicians. It is quite obvious, however, that individuals with a taste or smell loss may suffer a significant impairment to their quality of life, both aesthetically and emotionally. Smell and taste alert us to fires, poisonous fumes, leaking gas, and spoiled foods. For this reason, loss of smell is of particular concern to elderly individuals and to those who live alone. The natural pleasures associated with eating can be severely impaired in a person with a taste or smell loss or distortion. Smell and taste impairment can also lead to depression, especially in persons whose occupations (e.g., fireman, chef) critically depend upon these senses.

Differential olfactory perception of enantiomeric compounds by blind subterranean mole rats (Spalax ehrenbergi)

The behavior of mole rats (Spalax ehrenbergi) near pairs of enantiomeric compounds was examined in 901 two-choice experimental tests. Positioning of the nest and food store and the preferred location of the tested animal were used to assess attraction or aversion to the tested odorants. The results indicated that mole rats respond differentially to odors of stereoisomers (enantiomers of carvone, citronellol, and fechone). They responded to one enantiomer of each tested pair but were indifferent to or did not smell the other. Both sexes were attracted to the odor of R-(−)-carvone and repelled by the odor of (+)-citronellol. Females were attracted to the odor of (−)-fenchone while males had no preference. By contrast, all animals were indifferent to or did not smell the odor of S-(+)-carvone, (−)-citronellol, and (+)-fenchone. Further research to distinguish between these alternatives (indifference vs hyposmia/anosmia) is suggested.

Olfactory Disturbance in Pediatric Tracheotomy

Several studies have described hyposmia after laryngectomy. The most common mechanism invoked is a reduction in nasal airflow, leading to elevated olfactory detection thresholds. Children with nasal obstruction have been shown to also have elevated olfactory detection thresholds linked to reduced nasal airflow. A child with a tracheotomy is in some degree similar to a laryngectomee. These patients will have variable amounts of nasal airflow reduction proportional to the degree of suprastomal obstruction. Our concern was that this alteration in nasal airflow may cause hyposmia. Furthermore, if the olfactory system requires adequate early stimulation for normal development (as is the case with vision and hearing), tracheotomy would be suspected to cause persistent hyposmia even after decannulation. Thus decreased olfactory sensitivity, delayed olfactory experience, or both could interfere with a childs ability to recognize and identify odor stimuli. We studied children aged 4 to 16 years with upper airway obstruction requiring tracheotomy and compared their abilities to identify familiar odorants with those of a large group of normal control children. None of the children had intrinsic mucosal or olfactory pathology. Statistical analysis of the early data shows a significant reduction in olfactory identification scores in the patients with tracheotomies, both by Students t test and by the Wilcoxon rank sum test. Analysis of covariance confirmed age as an independent prognostic variable for identification ability. We therefore conclude that tracheotomy can reduce a childs ability to identify familiar odorants.

Role of C-reactive protein, reticulocyte haemoglobin content and inflammatory markers in iron and erythropoietin administration in dialysis patients

Aim:  C‐reactive protein (CRP) is an acute phase reactant protein, which becomes elevated in response to inflammation, infections or malignancies. These conditions are well known causes of bone marrow hyporesponsiveness and erythropoietin resistance in dialysis patients. The role of iron‐deficiency as a cause of hyporesponsiveness under these conditions is not clear. Reticulocyte haemoglobin content (CHr) is one of several iron indices used to determine iron deficiency in dialysis patients. The aim of this study is to evaluate the role of CRP and CHr in iron administration and anaemia management in dialysis patients