Citations

Established hospital palliative care consult services (PCCS) have been associated with reduced costs and length of stay, decreased symptom burden, and increased satisfaction with care. Using a retrospective case–control design, we analyzed administrative data of patients seen by PCCS while hospitalized at the Rochester, Minnesota Mayo Clinic hospitals from 2003 to 2008. The PCCS patients were matched to 3:1. A total of 1477 patients seen by the PCCS were matched with 4431 patients not seen. Costs for patients seen and discharged alive were US$35 449 (95% confidence interval [CI] US$34 157-US$36 686) compared to US$37 447 (95% CI US$36 734-US$38 126), without PCCS consultation. Costs for PCCS patients that died during hospitalization were US$54 940 (95% CI US$51 483-US$58 576) and non-PCCS patients were US$79 660 (95% CI US$76 614-US$83 398).

Abstract Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS‐PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome‐specific synthetic reviews and recommendations prepared by NPS‐PIA workgroups on depression, apathy, sleep, agitation, and psychosis.

AbstractBackgroundType 2 diabetes may increase the risk of amnestic mild cognitive impairment (aMCI) through Alzheimer's disease (AD)‐related and vascular pathology and may also increase the risk of nonamnestic MCI (naMCI) through vascular disease mechanisms. We examined the association of type 2 diabetes with mild cognitive impairment (MCI) and MCI subtype (aMCI and naMCI) overall and by sex.MethodsParticipants were Olmsted County, Minnesota residents (70 years and older) enrolled in a prospective, population‐based study. At baseline and every 15 months thereafter, participants were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of normal cognition, MCI, and dementia by a consensus panel. Type 2 diabetes was ascertained from the medical records of participants at baseline.ResultsOver a median 4.0 years of follow‐up, 348 of 1450 subjects developed MCI. Type 2 diabetes was associated (hazard ratio [95% confidence interval]) with MCI (1.39 [1.08–1.79]), aMCI (1.58 [1.17–2.15]; multiple domain: 1.58 [1.01–2.47]; single domain: 1.49 [1.09–2.05]), and the hazard ratio for naMCI was elevated (1.37 [0.84–2.24]). Diabetes was strongly associated with multiple‐domain aMCI in men (2.42 [1.31–4.48]) and an elevated risk of multiple domain naMCI in men (2.11 [0.70–6.33]), and with single domain naMCI in women (2.32 [1.04–5.20]).ConclusionsDiabetes was associated with an increased risk of MCI in elderly persons. The association of diabetes with MCI may vary with subtype, number of domains, and sex. Prevention and control of diabetes may reduce the risk of MCI and Alzheimer's disease.

Abstract Background Microbleeds have been associated with Alzheimer's disease (AD), although it is unclear whether they occur in atypical presentations of AD, such as the logopenic variant of primary progressive aphasia (lvPPA). We aimed to assess the presence and clinical correlates of microbleeds in lvPPA. Methods Thirteen lvPPA subjects underwent 3T T2*‐weighted and fluid‐attenuated inversion recovery magnetic resonance imaging and Pittsburgh compound B (PiB) positron emission tomography imaging. Microbleeds were identified on manual review and assigned a regional location. Total and regional white matter hyperintensity (WMH) burden was measured. Results Microbleeds were observed in four lvPPA subjects (31%), most commonly in the frontal lobe. Subjects with microbleeds were older, more likely female, and had a greater burden of WMH than those without microbleeds. The regional distribution of microbleeds did not match the regional distribution of WMH. All cases were PiB positive. Conclusions Microbleeds occur in approximately one third of subjects with lvPPA, with older women at the highest risk.

AbstractBackgroundIt is unclear whether self‐ or informant‐based subjective cognition better distinguishes emotional factors from early‐stage Alzheimer's disease (AD).MethodsHealthy members (n = 447) of the Arizona apolipoprotein E (APOE) cohort and their informants completed the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS).ResultsDecline on the MANS was endorsed by 30.6% of members and 26.2% of informants. Self‐ and informant‐based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8 [7.0] vs 58.8 [7.3] years, P = .003), 85% were APOE ε4 carriers (P < .0001), and they self‐endorsed decline earlier than informants (58.9 [39.2] vs 28.0 [40.4] months before MCI; P = .002).ConclusionsSelf‐ and informant‐based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self‐endorsed decline earlier than informants.

Background and Study Aims. The presence of an implantable electromechanical cardiac device (IED) has long been considered a relative contraindication to the performance of video capsule endoscopy (CE). The primary aim of this study was to evaluate the safety of CE in patients with IEDs. A secondary purpose was to determine whether IEDs have any impact on images captured by CE.Patients and Methods.A retrospective chart review of all patients who had a capsule endoscopy at Mayo Clinic in Scottsdale, AZ, USA, or Rochester, MN, USA, (January 2002 to June 2010) was performed to identify CE studies done on patients with IEDs. One hundred and eighteen capsule studies performed in 108 patients with IEDs were identified and reviewed for demographic data, method of preparation, and study data.Results.The most common indications for CE were obscure gastrointestinal bleeding (77%), anemia (14%), abdominal pain (5%), celiac disease (2%), diarrhea (1%), and Crohn’s disease (1%). Postprocedure assessments did not reveal any detectable alteration on the function of the IED. One patient with an ICD had a 25-minute loss of capsule imaging due to recorder defect. Two patients with LVADs had interference with capsule image acquisition.Conclusions.CE did not interfere with IED function, including PM, ICD, and/or LVAD and thus appears safe. Additionally, PM and ICD do not appear to interfere with image acquisition but LVAD may interfere with capsule images and require that capsule leads be positioned as far away as possible from the IED to assure reliable image acquisition.

Abstract Inhalation of cotton mill dust leads to the development of the occupational lung disease byssinosis in a portion of the exposed workers. Condensed tannins present in the dust have biologic activities consistent with the hypothesis that they are one of the etiologic agents for the disease. Inhalation of either cotton dust or tannin provokes an acute inflammatory response characterized by the influx of neutrophils into the airways. The secretion of a low-molecular-weight, lipid neutrophil chemotactic factor from the alveolar macrophages in response to tannin stimulation appears to be important in this inflammatory process. In these studies, the effect of tannin on the ability of alveolar macrophages and neutrophils to produce hydrogen peroxide was examined. Low concentrations of tannin itself induced a modest production of hydrogen peroxide from conditioned rabbit alveolar macrophages, while higher concentrations failed to induce peroxide production. In the presence of an independent stimulator of peroxide production (concanavalin A), tannin inhibited peroxide production at all concentrations examined. Aqueous extracts of cotton mill dust (CDE) had an identical effect on peroxide production in a manner that indicated that the tannin present in the dust was responsible for the effect. Like its direct effect on macrophage peroxide production, tannin induced modest peroxide production in human neutrophils. However, unlike its effect on macrophages, tannin enhanced the peroxide production induced by the presence of an independent stimulator (phorbol myristate acetate). CDE had a similar effect on peroxide production, but the dose-response curves suggested that only the high-molecular-weight polymers of tannin present in the CDE were able to enhance peroxide production. These results indicate that inhaled tannin would decrease the ability of resident alveolar macrophages to inactivate inhaled, potentially harmful cotton dust particles but would enhance the host-defense function of the recruited neutrophils. This difference in the action of tannin on neutrophils and macrophages may be of importance in the pathogenesis of byssinosis.

Abstract The condensed tannin present in cotton mill dust profoundly alters the functional capabilities of resident alveolar macrophages. Previous studies from this laboratory have shown that in vitro exposure of rabbit resident alveolar macrophages to condensed tannin significantly inhibits the ability of these cells to produce reactive oxygen intermediates or to ingest particles. In the present study, we demonstrate that condensed tannin also alters arachidonic acid (C20:4) metabolism in these cells. Exposure of rabbit resident alveolar macrophages to condensed tannin results in the time- and dose-dependent release of C20:4 from the membrane phospholipids. The release of C20:4 occurred only at tannin concentrations &gt; 25 µg/ml and was maximal 90 min after the onset of exposure. The EC50 for release was 75 µg/ml. Exposure to 100 µg/ml tannin resulted in the release of 20 ± 3% of the [14C]C20:4 incorporated in the cell membrane. In comparison, exposure to 160 µg/ml zymosan resulted in the release of 14 ± 4% of the [14C]C20:4. For both tannin and zymosan, phosphatidylcholine and phosphatidylinositol were the principal sources of the released C20:4. Approximately 63% of the C20:4 released after zymosan stimulation was further metabolized, mainly via the cyclooxygenase pathway. The major metabolites were 6-ketoprostaglandin F1α, prostaglandin F2α, and prostaglandin E2. In contrast, only 24% of the C20:4 released by tannin was subsequently further metabolized. The metabolites formed were essentially evenly distributed between products of the cyclooxygenase pathway and the lipoxygenase pathway. Exposure of alveolar macrophages to 50 µg/ml tannin for 30 min reduced the ability of the cells to subsequently incorporate C20:4 by 50 to 70%. In contrast, exposure of the cells to 160 mg/ml zymosan for 30 min had only a minimal effect on the subsequent ability of these cells to incorporate C20:4. These results indicate that tannin promotes C20:4 release, at least in part, by inhibiting its reacylation back into phospholipids, a mechanism that differs from that of zymosan.

Abstract A number of mechanisms participate in virus-induced asthma. Previously, we described enhanced basophil histamine release (HR) during an experimentally induced rhinovirus infection and after in vitro incubation of peripheral blood mononuclear cells (PBMC) with influenza virus. This study extends our previous observations and examines the effect of influenza A virus on basophil leukotriene C4 (LTC4) release as well as the effect of T-cell depletion on virus-enhanced basophil HR. PBMC were isolated from ragweed-allergic subjects and incubated with live influenza A virus or control medium (allantoic fluid). After incubation with influenza A, ragweed antigen (AgE) stimulated LTC4 and HR were enhanced (P &lt; 0.05). To further define the role of T cells in virus-enhanced basophil secretion, PBMC were isolated and divided into two aliquots. In one aliquot, T cells were removed by magnetic bead separation of mouse monoclonal anti-CD3-coated lymphocytes. T-cell-depleted and nontreated PBMC suspensions were incubated with influenza A or control medium, collected, and challenged with AgE to release histamine. Basophil HR was enhanced in the virus-treated group of PBMC that had not undergone T-cell depletion. In contrast, virus incubation did not enhance HR in the T-cell-depleted fraction. Finally, preliminary analysis of the supernate from virus-treated leukocytes indicates the presence of interferon-γ. These findings suggest that T cells, and their cytokine products, play an integral role in the process by which viruses enhance basophil HR.

Abstract A donor lung is injured during preservation and is generally thought to be further injured by reperfusion on transplantation. Donor lungs from 15 adult male Lewis rats preserved by flush perfusion with cold Marshall's solution at 4° C were examined by scanning and by quantitative transmission electron microscopy after 2, 4, or 7 h of storage at 4° C and after transplantation (syngeneic) at 4 or 12 h (six animals per time interval). During preservation of the donor lung, capillary morphology changed rapidly. Both endothelial cells and type I pneumonocytes thinned (surface/volume ratio increased by 2 h in both; P &lt; 0.001). Pericapillary edema developed involving the blood-gas barrier. Basement membrane thickness increased significantly (P &lt; 0.001). Occasional breakage of the endothelial cell sheet occurred after 4 h of preservation, but even after 7 h of preservation there was no evidence of irreversible cell damage. The lamellar bodies of type II pneumocytes aggregated. Changes increased in severity with increase in preservation time. After transplantation, type I and type II pneumonocytes recovered after 12 h, but it took longer for the endothelial cell morphology to recover. Edema decreased rapidly during the first 4 h, despite the number of adherent neutrophils increasing 3-fold. The pulmonary capillaries of the transplanted lung showed no structural evidence of additional reperfusion injury, indicating a satisfactory method of preservation.