IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression.

Interleukin-13 (IL-13) shares many, but not all, of the properties of the prototypic T-helper type 2 (Th2) cytokine IL-4, but its role in allergen-driven T-cell responses remains poorly defined. We hypothesized that allergen stimulation of peripheral blood T cells from patients with atopic disease compared with non-atopic controls results in elevated IL-13 synthesis in the context of a 'Th2-type' pattern. Freshly isolated peripheral blood mononuclear cells (PBMC) obtained from sensitized atopic patients with allergic disease, and non-atopic control subjects, were cultured with the allergens Phleum pratense (Timothy grass pollen) or Dermatophagoides pteronyssinus (house dust mite) and the non-allergenic recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). Supernatant concentrations of IL-13, along with IL-5 and interferon-gamma (IFN-gamma) (Th2- and Th1-type cytokines, respectively) were determined by enzyme-linked immunosorbent assay (ELISA). Allergen-induced IL-13 and IL-5 production by T cells from patients with allergic disease was markedly elevated (P = 0.0075 and P = 0.0004, respectively) compared with non-atopic controls, whereas IFN-gamma production was not significantly different. In contrast to allergen, the prototypic Th1-type antigen M. tuberculosis PPD induced an excess of IFN-gamma over IL-13 and IL-5 production, and absolute concentrations of cytokines were not affected by the presence or absence of atopic disease. Addition of exogenous recombinant IFN-gamma or IL-12, cytokines known to inhibit Th2-type responses, significantly inhibited allergen-driven production of both IL-13 and IL-5, but not T-cell proliferation, whereas exogenous IL-4 did not significantly affect production of IL-13 or IL-5. We conclude that allergen-specific T cells from atopic subjects secrete elevated quantities of IL-13 compared with non-atopic controls, in the context of a Th2-type pattern of cytokine production.     

Deafferentation-induced caspase-3 activation and DNA fragmentation in chick cochlear nucleus neurons

Cochlea removal severs peripheral processes of cochlear ganglion cells and permanently abolishes afferent input to nucleus magnocellularis (NM) neurons. Deafferented chick NM neurons undergo a series of morphologic and metabolic changes, which ultimately trigger the death of 20%–40% of neurons. Previous studies suggested that this cell specific death involves activation of the intrinsic apoptotic pathway, including increased presence of cytochrome c and active caspase-9 in the cytoplasm of deafferented NM neurons. Interestingly, however, both markers were detected pan-neuronally, in both degenerating and surviving NM neurons [Wilkinson BL, Elam JS, Fadool DA, Hyson RL (2003) Afferent regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus. Neuroscience 120:1071–1079]. Here, we provide evidence for the increased appearance of late apoptotic indicators and describe novel characteristics of cell death in deafferented auditory neurons. Young broiler chickens were subjected to unilateral cochlea removal, and brainstem sections through NM were reacted for active caspase-3 and terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL). Caspase-3 activation is observed in the cytoplasm of both dying and surviving deafferented NM neurons 24 h to 7 days following cochlea removal, suggesting that caspase-3, usually considered an “executioner” of apoptotic death, may also function as a “modulator” of death. In addition, we find that TUNEL labeling of degraded DNA is observed in deafferented NM. In contrast to upstream apoptotic markers, however, TUNEL labeling is restricted to a subpopulation of deafferented neurons. Twelve hours following cochlea removal, TUNEL labeling is observed as punctate accumulations within nuclei. Twenty-four hours following cochlea removal, TUNEL accumulates diffusely throughout neuronal cytoplasm in those neurons likely to die. This cytoplasmic TUNEL labeling may implicate mitochondrial nucleic acid degradation in the selective death of some deafferented NM neurons. Our study examines the subcellular distributions of two prominent apoptotic mediators, active caspase-3 and TUNEL, relative to known histochemical markers, in deafferented NM; provides new insight into the apoptotic mechanism of cell death; and proposes a role for mitochondrial DNA in deafferentation-induced cell death.     

Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation

Sixty-three recipients of an allogeneic marrow transplant were screened for the occurrence of cytomegalovirus (CMV) infection and clinical parameters possibly predicting the development of CMV disease in a retrospective study. Blood and urine samples obtained from these patients were screened weekly after bone marrow transplantation (BMT) for the presence of CMV by polymerase chain reaction (PCR) and virus culture technique. Forty-six of the 63 patients studied were found to be CMV-positive by PCR technique in blood and urine samples at a median of 29 days after BMT. In 33 of these 46 patients, CMV could be cultured from urine samples and 16 of the 46 had culture-positive viremia. Twenty-eight of these 46 PCR-positive patients developed CMV disease. Whereas PCR assays showed an optimal negative predictive value and sensitivity for the development of CMV disease, their positive predictive value was 61% and could not be remarkably increased when culture-proven viruria (64%) and viremia (69%) were considered. Acute graft-versus-host disease (GVHD) grade 2 to 4 (P < .05), but not underlying disease, conditioning therapy, or GVHD prophylaxis, was associated with CMV infection. On day +49, a remarkable decrease (P < .001) in the lymphocyte count, as well as in the absolute number of CD4+, CD8+, and CD56+ lymphocytes, occurred only among the patients who later developed CMV disease. The decrease of all of these cell counts, but predominantly the CD4+ T cells, to less than 100/microL on day +49 after BMT showed a very high positive predictive value (100%) for the development of CMV disease in patients with PCR-proven viremia. Persisting CD4 lymphopenia after antiviral therapy was only observed in patients who finally died of CMV disease. Thus, immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.     

Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma

The effect of pharmacologic agents on mast cell mediator release was investigated in vivo. Eight atopic asthmatic subjects with airways relatively unreactive to nonspecific stimuli (geometric mean PC20 methacholine, 4.0 mg/ml) underwent single-concentration allergen challenge before (control) or after inhaling albuterol 200 micrograms, cromolyn sodium 20 mg, or 0.9% sodium chloride placebo. Six of the same subjects also underwent allergen challenge after pretreatment with ipratropium bromide, 1 mg. Airway responses to pharmacologic agents and bronchial challenge were measured by change in both specific airway conductance (SGaw) and FEV1. Mast cell mediator release was monitored by serial change in plasma histamine and, in addition, serum neutrophil chemotactic factor (NCF) on the placebo, albuterol, and cromolyn sodium challenge days. Control and placebo allergen challenges were associated with repeatable mean maximal falls in SGaw (48.5 versus 49.6%) and FEV1 (25.7 versus 25.5%). The mean increments in plasma histamine were not significantly different on the control (0.17 to 0.44 ng/ml) or placebo challenge days (0.18 to 0.64 ng/ml), with maximal levels occurring 5 min after challenge. A sustained increase in NCF was identified on the placebo challenge day (155.0% above baseline). Pretreatment with albuterol abolished any significant bronchoconstriction, with mean maximal falls in SGaw and FEV1 after challenge of 7.5 and 1.4%, respectively. These changes in airway caliber were not associated with any significant increment in mean plasma histamine (0.17 to 0.22 ng/ml) or serum NCF (4.1% increase). Cromolyn sodium pretreatment, while attenuating the airway response, was still associated with significant falls in SGaw (22.7%) and FEV1 (7.3%) and increases in plasma histamine (0.18 to 0.27 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained Use of the Impella 5.0 Heart Pump Enables Bridge to Clinical Decisions in 34 Patients

We studied whether sustained hemodynamic support (>7 d) with the Impella 5.0 heart pump can be used as a bridge to clinical decisions in patients who present with cardiogenic shock, and whether such support can improve their outcomes.We retrospectively reviewed cases of patients who had Impella 5.0 support at our hospital from August 2017 through May 2019. Thirty-four patients (23 with cardiogenic shock and 11 with severely decompensated heart failure) underwent sustained support for a mean duration of 11.7 ± 9.3 days (range, ≤48 d). Of 29 patients (85.3%) who survived to next therapy, 15 were weaned from the Impella, 8 underwent durable left ventricular assist device placement, 4 were escalated to venoarterial extracorporeal membrane oxygenation support, and 2 underwent heart transplantation. The 30-day survival rate was 76.5% (26 of 34 patients). Only 2 patients had a major adverse event: one each had an ischemic stroke and flail mitral leaflet. None of the devices malfunctioned.Sustained hemodynamic support with the Impella 5.0 not only improved outcomes in patients who presented with cardiogenic shock, but also provided time for multidisciplinary evaluation of potential cardiac recovery, or the need for durable left ventricular assist device implantation or heart transplantation. Our study shows the value of using the Impella 5.0 as a bridge to clinical decisions.     

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN)

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.     

ARTICLE: Oral health status of older adults in Kentucky: results from the Kentucky Elder Oral Health Survey

The purpose of the Kentucky Elder Oral Health Survey (KEOHS) was to assess the oral health status of Kentuckians 65 and older. The KEOHS consisted of a self‐administered questionnaire and a clinical examination. Recruitment occurred from May 2002 through March 2005 of persons aged 65 and older (n = 1,386) whose functional ability was classified by residential setting. Independent elders living in their own homes were designated as “well‐elders,” those who lived in skilled nursing facilities and who were functionally dependent were designated as “nursing home elders,” and those older adults who were considered frail were designated as “homebound elders.” Significant associations were found between the functional ability of the elders and demographic characteristics. While elders who were homebound reported the highest rate of barriers to care, dental insurance, affordability, and transportation were consistently reported as barriers for all groups of elders. This study has established the baseline oral health status of older adults in Kentucky and the data show differences that exist for various community living situations.     

Impact of periodontitis on oral health-related quality of life

ObjectivesTo investigate the impact of chronic periodontitis on oral health-related quality of life (OHRQoL) using the full version of the Oral Health Impact Profile (OHIP-49) and the Oral Health Quality of Life-UK (OHQoL-UK) questionnaires.Methods89 patients with chronic periodontitis and 89 age- and gender-matched patients without chronic periodontitis were recruited. OHIP-49 and OHQoL-UK were self-completed by participants and mean scores were calculated for each item, domain and the overall summary score (additive method) for each instrument in each group.ResultsThe mean age of participants was 47 ± 9 years, and the periodontitis patients had, on average, 33 ± 23 sites demonstrating probing depths ≥5 mm. OHRQoL was significantly poorer in the periodontitis patients compared to the periodontally healthy patients, when assessed by either instrument. When considering OHIP-49, fourteen of the forty-nine items indicated significantly poorer OHRQoL in the periodontitis group, and the overall OHIP-49 summary score was 48.6 ± 32.0 for periodontitis patients compared to 36.8 ± 29.8 in periodontally healthy patients (p < 0.01). When considering OHQoL-UK, fifteen of the sixteen items indicated significantly poorer OHRQoL in the periodontitis group, and the overall OHQoL-UK summary score was 47.1 ± 9.7 for periodontitis patients compared to 53.1 ± 11.3 in periodontally healthy patients (p < 0.01). Overall, those items with the greatest differences between periodontitis patients and the healthy group related to psychological concerns, halitosis, pain and aesthetics.ConclusionSubjects with periodontitis report substantial functional, physical, psychological, and social OHRQoL impacts.Clinical significanceThis study has identified that patients with chronic periodontitis report significantly poorer oral health-related quality of life (OHRQoL) than age- and gender-matched periodontally healthy patients, with significant functional, social and psychological impacts. Clinicians should be aware of the impacts that periodontitis may have on OHRQoL, including psychological concerns, halitosis, pain and aesthetics.     

DSM-5 PTSD's symptom dimensions and relations with major depression's symptom dimensions in a primary care sample

Existing literature indicates significant comorbidity between posttraumatic stress disorder (PTSD) and major depression. We examined whether PTSD’s dysphoria and mood/cognitions factors, conceptualized by the empirically supported four-factor DSM-5 PTSD models, account for PTSD's inherent relationship with depression. We hypothesized that depression's somatic and non-somatic factors would be more related to PTSD's dysphoria and mood/cognitions factors than other PTSD model factors. Further, we hypothesized that PTSD's arousal would significantly mediate relations between PTSD's dysphoria and somatic/non-somatic depression. Using 181 trauma-exposed primary care patients, confirmatory factor analyses (CFA) indicated a well-fitting DSM-5 PTSD dysphoria model, DSM-5 numbing model and two-factor depression model. Both somatic and non-somatic depression factors were more related to PTSD's dysphoria and mood/cognitions factors than to re-experiencing and avoidance factors; non-somatic depression was more related to PTSD's dysphoria than PTSD's arousal factor. PTSD's arousal did not mediate the relationship between PTSD's dysphoria and somatic/non-somatic depression. Implications are discussed.