Spirometric reference equations for Swedish adults

New spirometric reference equations for Swedish adults are required. Three different older sets of reference equations clinically used in Sweden have various drawbacks and the recently published ‘The Global Lung Function 2012 (GLI) equations’ have been shown not to be adequate for Swedish normal, healthy non‐smokers. We have recently concluded that a piecewise linear model presented by Lubinski and Gólczewski accurately describes the distribution of spirometric variables in a large Swedish random population sample. This piecewise linear model also offers the important advantage of implementing easily physiologically interpretable coefficients. The present study aimed at presenting piecewise linear reference equations for Swedish adults based on a random population sample of 6685 individuals aged 25–75 years. Predicted normal values by the piecewise linear reference equations and lower limit normal (LLN) were compared with the three reference equations frequently used clinically in Sweden and the GLI equations. We found predicted normal values according to the present piecewise linear reference equations close to 100% predicted normal as expected, whereas the other equations either overestimated or underestimated normal subjects. Concerning LLN, the present equations, i.e. 1·645 × RSD, showed the least deviation from the expected 5% and, e.g., the GLI equations systematically identified too few subjects below LLN. We conclude that the present piecewise linear reference equations, based on a relatively large general population sample, ought to be considered for clinical use in Sweden. Application of 1·645 × RSD below predicted value gave an acceptably accurate LLN.     

Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials.

OBJECTIVE: The authors explored the effect of galantamine on behavioral symptoms in Alzheimer disease (AD). METHODS: Data were pooled from 2,033 subjects with mild-to-moderate AD who had participated in one of three randomized, double-blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects included in this post hoc analysis had received treatment with either placebo (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg. Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations; 2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition, elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant motor behavior. RESULTS: At endpoint, mean changes from baseline in NPI scores were significantly different between galantamine-treated subjects and placebo-treated subjects, favoring galantamine for several measures: total NPI, individual domains of agitation/aggression, anxiety, disinhibition, and aberrant motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was small. CONCLUSIONS: In this pooled sample of more than 2,000 subjects with mild-to-moderate AD, those who received galantamine therapy experienced modestly better, but statistically significant, outcomes in their behavioral symptoms than placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and aberrant motor behaviors may represent a specific group of cholinergic-responsive behavioral symptoms.     

O2 consumption,aerobic glycolysis and tissue phosphagen content during activation of the NA+/K+ pump in rat portal vein

Oxygen consumption, lactate production and tissue contents of ATP, phosphocreatine (PCr) and lactate were measured following readdition of K⁺ to K⁺-depleted rat portal veins, in order to study the energy turnover associated with Na⁺/K⁺ pumping. During incubation in K⁺-free medium at 37° C spontaneous contractions disappeared in 10–20 min. Readdition of K⁺ (5.9 mM) after 40 min K⁺-free incubation caused hyperpolarization of the cell membrane for the first 5–10 min and then gradual depolarization with return of spontaneous action potentials and contractions by 10–20 min. During the first 4–6 min after K⁺ readdition aerobic lactate production was about doubled and then gradually returned to the original level (0.17 mol/min g) at about 20 min. The increase in glycolytic rate was prevented by 1 mM ouabain. In contrast, O₂ consumption (in K⁺-free medium, 0.38 mol/min g) rose by about 10% when K⁺ was added and this increase lasted about 5 min. By 8 min after K⁺ addition the increased glycolysis and oxidative phosphorylation had accounted for each about the same amount of extra ATP generation over that extrapolated from the steady rate before K⁺ addition. The average total increase in ATP turnover in the first 8 min was 15%. During this period there was no change in the cellular content of ATP, PCr, or extractable ADP. The results indicate that Na⁺/K⁺ pumping utilizes a relatively small share of the total energy turnover in the vascular smooth muscle but is to a large extent dependent on aerobic glycolysis and therefore a major site of carbohydrate usage.     

Threats to Life in Residential Structure Fires

Introduction. Firefighters are taught that heat, oxygen deprivation, andcarbon monoxide (CO) are the primary threats to life in residential structure fires, andthey are taught to search for victims on the fire floor first, andthen floors above. The objective of this study was to gather data regarding oxygen, CO, andheat conditions inside a realistic house fire, to examine the validity of these teachings. Methods. During six live-burn training evolutions in a two-story wood-frame house, metering for oxygen levels, CO levels, andtemperature was conducted. Except where noted, all readings were taken 24 inches off the floor, to simulate the location of a crawling victim or firefighter. Readings were hand-recorded on a convenience basis by firefighters stationed outside the building, near the meters. Results. Of the 35 oxygen levels recorded, the lowest was 18.2%, with only 12 readings below 20%. Three of 16 first-floor readings were below 20%, whereas nine of 19 second-floor readings were below 20% (p = 0.07). First- andsecond-floor readings were comparable (mean 20.3% vs. 19.9%, p = 0.11). Except for one reading of 1,870 ppm, all CO readings at the ceiling exceeded the 2,000-ppm limit of the meters. Of the 34 CO levels recorded 24 inches off the floor, 29 (76%) exceeded the permissible exposure limit of 50 ppm, with the highest reading being 1,424 ppm, well above the “immediately dangerous to life andhealth” level of 1,200 ppm. None of the 20 CO levels recorded on the first floor exceeded the 30-minute exposure limit of 800 ppm, whereas seven of 14 second-floor readings exceeded this limit (p < 0.001). While ceiling temperatures frequently exceeded the 1,000°F limit of the meters, none of 16 readings taken 24 inches off the floor exceeded 137°F. First- andsecond-floor temperatures were comparable (mean 88.5°F vs. 90.1°F, p = 0.9). Conclusions. In residential structure fires, CO poses a greater threat to victims andfirefighters than does oxygen deprivation or heat. Emergency medical services personnel should consider CO toxicity in all fire victims. Conditions on the floor above a fire are at least as adverse as those on the fire floor.     

A recombinant autoantigen derived from the human (u1) small nuclear rnp-specific 68-kd protein

A human liver complementary DNA expression library was screened using sera from patients with high titers of autoantibodies, to search for clones expressing major autoantigens that are relevant in connective tissue diseases. One of the clones isolated expressed a major epitope(s) that was immunoreactive with anti-U1 RNP sera, as shown by several techniques. Affinity-purified autoantibodies from the cloned RNP protein specifically recognized the 68-kd U1 RNP protein of HeLa cell nuclear extracts. All sera containing anti-U1 RNP antibodies detected by immunodiffusion, counterimmuno-electrophoresis, or immunoblotting also recognized the cloned RNP protein. The RNP antigen-expressing bacterial colonies and the partially purified cloned RNP fusion protein have been applied to fast and sensitive immunologic assays for the detection and quantification of anti-U1 RNP antibodies.     

Perioperative assessment of platelet function by Thromboelastograph® Platelet Mapping™ in cardiovascular patients undergoing non-cardiac surgery

Five percent of patients on dual antiplatelet therapy after coronary artery stent implantation will need non-cardiac surgery within the first year of therapy, and many more will need surgery later on. A function assay that evaluates platelet reactivity and inhibition by drug therapy is beneficial for such patients. Platelet Mapping assay (PM?) using the TEG^® analyzer was tested in surgical patients. After IRB approval, 60 patients on combined aspirin and clopidogrel therapy were consented and enrolled. The TEG^® maximal amplitude (MA) and the percentage (%) platelet inhibition were recorded and analyzed. Fifty-seven patients (mean age 65.7 ± 10.9 years) had preoperative data only. Distribution of preoperative ADP (43.6 ± 24.4 %) and AA inhibition (52.8 ± 30.2 %) was determined, as well as for the preoperative MA ADP (43.1 ± 15.9 mm) and MA AA (37.2 ± 19.6 mm), showing an offset of the effect of both medications starting from day 3. Patients with complete pre- and postoperative data were stratified depending on duration off antiplatelet therapy (≤3 days, 3–7 days and >7 days): n = 27, ADP % preop inhibition (43.2 ± 21.6 %), ADP % postop inhibition (32.3 ± 18.3 %), p = 0.048. Distribution of immediate pre- and post- ADP and AA % inhibitions, showing a possible reduction in Δ of inhibition for clopidogrel at 3 days, were also assessed. Conclusion: According to the findings, the TEG^® PM? assay might be a feasible approach to objectively evaluate the effects of aspirin and clopidogrel during the perioperative period and potentially guide drug management.