Severe rhinosinusitis

Rhinosinusitis is diagnosed frequently in clinical practice, but the term may in fact encompass a wide spectrum of diseases. Inflammation of the nasal and sinus mucosa can arise from various causes and lead to different sequelae. Moreover, the term rhinosinusitis is more accurate than sinusitis. Causes range from a viral infection leading to the common cold to an invasive, fungal infection. An accurate diagnosis is important because effective therapy is available if recognized early and if specific therapy is used. Importantly, there is a close relationship between upper and lower airway disease and each have unique structural and functional differences that make an understanding of rhinosinusitis important not only for upper airway disease, but also for the management of asthma. All too often, rhinosinusitis becomes chronic and this becomes a challenge because medical therapy may not be sufficient to control disease. Finally, we should note that the differential diagnosis of rhinosinusitis is extensive and physicians should place heavy emphasis not only on the history, but also on appropriate imaging studies. A normal exam does not rule out the possibility or rhinosinusitis. Finally, we should emphasize that effective treatment is dependent on the etiology of the symptoms but also dependent on whether it is acute or chronic.     

Neural correlates of cross-modal binding

Little is known about how the brain binds together signals from multiple sensory modalities to produce unified percepts of objects and events in the external world. Using event-related functional magnetic resonance imaging (fMRI) in humans, we measured transient brain responses to auditory/visual binding, as evidenced by a sound-induced change in visual motion perception. Identical auditory and visual stimuli were presented in all trials, but in some trials they were perceived to be bound together and in others they were perceived as unbound unimodal events. Cross-modal binding was associated with higher activity in multimodal areas, but lower activity in predominantly unimodal areas. This activation pattern suggests that a reciprocal and 'competitive' interaction between multimodal and unimodal areas underlies the perceptual interpretation of simultaneous signals from multiple sensory modalities.     

The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder

This research represents the first controlled treatment study of hypnosis and cognitive- behavioral therapy (CBT) of acute stress disorder (ASD). Civilian trauma survivors (N=87) who met criteria for ASD were randomly allocated to 6 sessions of CBT, CBT combined with hypnosis (CBT-hypnosis), or supportive counseling (SC). CBT comprised exposure, cognitive restructuring, and anxiety management. CBT-hypnosis comprised the CBT components with each imaginal exposure preceded by a hypnotic induction and suggestions to engage fully in the exposure. In terms of treatment completers (n=69), fewer participants in the CBT and CBT-hypnosis groups met criteria for posttraumatic stress disorder at posttreatment and 6-month follow-up than those in the SC group. CBT-hypnosis resulted in greater reduction in reexperiencing symptoms at posttreatment than CBT. These findings suggest that hypnosis may have use in facilitating the treatment effects of CBT for posttraumatic stress.     

Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative

OBJECTIVE: To examine the prevalence and correlates of self-reported urogenital symptoms (dryness, irritation or itching, discharge, dysuria) among postmenopausal women aged 50-79. DESIGN: A cross-sectional analysis based on n=98,705 women enrolled in the US-based Women's Health Initiative observational study and clinical trials. Urogenital symptoms, symptom severity (mild, moderate, severe), and all covariates were self-reported through questionnaires at enrollment. Prevalence rates of each urogenital symptom were examined and logistic regression was used to identify potential correlates. RESULTS: Prevalence rates for each symptom were: dryness, 27.0%; irritation or itching, 18.6%; discharge, 11.1%; and dysuria, 5.2%. Four factors were correlated with two or more symptoms: Hispanic ethnicity (adjusted odds ratio (AOR)=2.1-3.1 versus white women across all symptoms), obesity (AOR=2.2 severe discharge versus none, AOR=3.6 severe irritation/itching versus none), treated diabetes (pills or shots) compared to no diabetes (AOR=2.4 severe dysuria versus none, AOR=3.2 severe irritation/itching versus none), and vaginal cream HRT/ERT compared to those who never used HRT/ERT (AOR=4.4 severe dryness versus none, AOR=4.6 severe irritation/itching versus none). Factors not associated with the symptoms included sexual activity, age, years since menopause, current smoking, marital status, gravidity, and natural versus surgical menopause. CONCLUSIONS: This is the first report to document urogenital symptoms by race/ethnicity among an exclusively postmenopausal population. We found an elevated prevalence of urogenital symptoms among women who are Hispanic, obese, and/or diabetic. Confirmation of our findings in these subgroups, and, if confirmed, analysis on why these populations are at greater risk, are areas for future research.     

Hepatocyte proliferation is the possible mechanism for the transient decrease in liver injury during steatosis stage of alcoholic liver disease

Steatosis is a frequent pathologic stage in alcoholic liver disease (ALD). Although the mechanisms for increased susceptibility of steatotic liver to injury have been postulated, the ability of these hepatocytes to proliferate and withstand injury is unknown. There are conflicting reports on the status of hepatocyte regeneration following chronic alcohol ingestion. Hence, the objective of this study was to investigate the temporal dynamics between the pattern of liver injury and hepatocyte proliferation during the steatosis stage of ALD. Alcoholic steatosis was induced in male Sprague-Dawley rats by feeding an ethanol (EtOH)-containing Lieber-DeCarli liquid diet for a period of 5 weeks. Microvesicular steatosis was evident in H&E sections by three weeks in the EtOH-treated rats, which further developed into panlobular macrovesicular steatosis by 5 weeks. Plasma transaminase activities indicated progressive increase in liver injury peaking at 3 weeks with significant but mild decrease at 4 and 5 weeks. CYP2E1 protein and activity was significantly increased in EtOH-fed rats as measured by Western blot and pNP hydroxylation assay. PCNA analysis of liver sections indicated that EtOH-treated rats had a significantly higher number of cells in S phase of cell division at weeks 1 (3.20 +/- 0.19), 2 (7.03 +/- 0.92), and 3 (4.23 +/- 1.41) when compared to controls (1.5 +/- 0.22). NF-kappaB DNA binding and Cyclin D1 proteins increased significantly in the EtOH-treated rats corresponding with enhanced hepatic proliferation. These data suggest the transient decline in liver injury during alcoholic steatosis is due to enhanced NF-kappaB-dependent hepatocyte proliferation.     

Significance of PBMC response of rheumatic fever patients and control individuals to immunodominant streptococcal M5 protein epitopes

β-hemolytic streptococcal infection in developing countries still causes thousands of cases of Rheumatic Fever (RF). Molecular mimicry between streptococcal M protein (strep M) and heart components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility, which is linked to different HLA-DR alleles in different populations. In our hands, RF was significantly associated to HLA-DR7/53. Previous work in our lab has shown that heart-infiltrating T cells that simultaneously recognize strep M and heart proteins. Further, such T cells predominantly recognized the 81-103 strep M5 epitope. In this work, we analysed the proliferative response of peripheral blood mononuclear cells of 99 RF patients and 40 normal controls. Eighty-nine of the RF patients were HLA-typed. As among heart-infiltrating T cells, the 81-103 strep M5 protein epitope is the most frequently recognized epitope among RF PBMC (35.4%), against a 7.5% frequency of proliferation among normal controls (p=0.0018, chi square). However, the 81-103 epitope was as frequently recognized by HLA-DR7,53 positive as by negative individuals (45.2% vs 54.8%, respectively). Taken together, the results suggest that the 81-103 strep M5 epitope may be the immunodominant epitope, “promiscuously” recognized by T cells in a genetically diverse population. The demonstration that molecular mimicry is targeted to a discrete immunodominant “promiscuous” epitope in strep M5 may allow the development of a safe anti-streptococcal synthetic vaccine devoid of such epitopes.     

The influence of normal human ageing on automatic movements

There is evidence that aged normal subjects have more difficulty in achieving automaticity than young subjects. The underlying central neural mechanism for this phenomenon is unclear. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effect of normal ageing on automaticity. Aged healthy subjects were asked to practice self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Although it took more time, most aged subjects eventually performed the tasks automatically at the same level as the young subjects. Functional MRI results showed that, for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. While performing automatic movements, aged subjects had greater activity in the bilateral anterior lobe of cerebellum, premotor area, parietal cortex, left prefrontal cortex, anterior cingulate, caudate nucleus and thalamus, and recruited more areas, including the pre-supplementary motor area and the bilateral posterior lobe of cerebellum, compared to young subjects. These results indicate that most healthy aged subjects can perform some complex motor tasks automatically. However, aged subjects appear to require more brain activity to perform automatically at the same level as young subjects. This appears to be the main reason why aged subjects have more difficulty in achieving automaticity.     

Vascular Endothelial Growth Factor/Vascular Permeability Factor Is Temporally and Spatially Correlated with Ocular Angiogenesis in a Primate Model

Ischemia often precedes neovascularization. Inocular neovascularization, such as occurs in diabetic retinopathy, a diffusible angiogenic factor has been postulated to be produced by ischemicretina and to lead to neovascularization of theretina, optic nerve, or iris. However, no angiogenic factor has been conclusively identified that satisfies this hypothesis. Vascular endothelial growth factor/vascular permeability factor, hereafter referred to as VEGF, is a likely candidate for an ocular angiogenic factor because it is a secreted mitogen, specific for endothelial cells, and is upregulated by hypoxia. We investigated the association of VEGF with the development of experimental iris neovascularization in the cynomolgus monkey. Following theproduction of retinal ischemia by laser occlusion of all branch retinal veins, VEGF was increased in the aqueous fluid, and the aqueous VEGF levels changed synchronously and proportionally with the severity of iris neovascularization. Northern analysis and in situ hybridization revealed that VEGF messenger RNA is upregulated in the ischemic retina. These observations support the hypothesis that ocular neovascularization is regulated by a diffusible factor and identify VEGF as a likely candidate for a retina-derived vascular permeability and angiogenesis factor in vivo.     

Identification of a fibronectin-binding protein from Staphylococcus epidermidis

Staphylococcus epidermidis has been reported to bind to a number of host cell extracellular matrix proteins, including fibronectin. Here we report the identification of a fibronectin-binding protein from S. epidermidis. A phage display library of S. epidermidis genomic DNA was constructed and panned against immobilized fibronectin. A number of phagemid clones containing overlapping inserts were identified, and one of these clones, pSE109FN, contained a 1.4-kb insert. Phage pSE109FN was found to bind to fibronectin but not to collagen, fibrinogen, laminin, or vitronectin. However, pSE109FN also bound to heparin, hyaluronate, and plasminogen, although to a lesser extent than it bound to fibronectin. Analysis of The Institute for Genomic Research S. epidermidis genome sequence database revealed a 1.85-kb region within a putative 30.5-kb open reading frame, to which the overlapping DNA inserts contained within the fibronectin-binding phagemids mapped. We have designated the gene encoding the fibronectin-binding domain embp. A recombinant protein, Embp32, which encompassed the fibronectin-binding domain of Embp, blocked the binding of S. epidermidis, but not the binding of Staphylococcus aureus, to fibronectin. In contrast, a recombinant protein, FnBPB[D1-D4], spanning the fibronectin-binding domain of the S. aureus fibronectin-binding protein FnBPB, blocked binding of S. aureus to fibronectin but had a negligible effect on the binding of S. epidermidis.