A comparison of single breath and re-breathe diffusing capacity in emphysema patients and controls

In emphysema patients, gas dilutional alveolar volume is underestimated by a 10s single breath maneuver at total lung capacity (TLC) compared with re-breathing at functional residual capacity (FRC); corresponding underestimation of single breath diffusing capacity (DLCO) in emphysema has not been demonstrated. The purpose of this study was to quantify the degree to which re-breathe DLCO at FRC (DLCO(RB)) differs from single breath DLCO at TLC (DLCO(SB)) in emphysema. In 37 consecutively recruited patients with moderate to severe emphysema (FEV1/FVC 40%±10% predicted), DLCO(RB) as % predicted of 91 controls without cardiopulmonary disease was 79%±24%, significantly greater than % predicted DLCO(SB) (44%±19%; p<0.0001). DLCO(RB)/DLCO(SB) was inversely proportional to FEV1% predicted (R = -0.47, p=0.004), and FEV1/FVC (R = -0.54, p<0.001). These data indicate that a 10s single breath DLCO maneuver progressively under-represents re-breathe lung diffusing capacity in emphysema as airflow obstruction increases.     

Respiratory mechanics in COPD patients who failed non-invasive ventilation: Role of intrinsic PEEP

The purpose was to determine if 2 weeks of buspirone suppressed post-hypoxic breathing instability and pauses in the C57BL/6J (B6) mouse. Study groups were vehicle (saline, n=8), low-dose (1.5 mg/kg, n=8), and high-dose buspirone (5.0 mg/kg, n=8). Frequency, measured by plethysmography, was the major metric, and a pause defined by breathing cessation >2.5 times the average frequency. Mice were tested after 16 days of ip injections of vehicle or drug. On day 17, 4 mice in each group were tested after buspirone and the 5-HT(1A) receptor antagonist, 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinyl-benzamide (p-MPPI, 5 mg/kg). A post-hypoxic pause was present in 6/8 animals given vehicle and 1/16 animals given buspirone at either dose, but always present (8/8) with p-MPPI, regardless of buspirone dose. Post-hypoxic frequency decline was blunted by buspirone (-10% vehicle vs. -5% at both doses) and restored by p-MPPI; ventilatory stability as described by the coefficient of variation which was reduced by buspirone (p<0.04) was increased by p-MPPI (0.01). In conclusion, buspirone administration after 2 weeks acts through the 5-HT(1A) receptor to reduce post-hypoxic ventilatory instability in the B6 strain.     

Skeletal muscle mass,fat mass,and hip bone mineral density in elderly women with hip fracture

Soft tissue body composition strongly affects bone health. Our aim was to investigate the relationship between both skeletal muscle mass (SMM) and fat mass (FM) and femoral bone mineral density (BMD) in a sample of elderly women with hip fracture. We assessed 293 of 325 hip fracture women admitted consecutively to a rehabilitation hospital. Soft tissue body composition and BMD were assessed by dual-energy X-ray absorptiometry (DXA), 23.2 ± 7.7 (mean ± SD) days after fracture occurrence. BMD was measured at four sites (neck, total femur, trochanter, intertrochanteric area) in the unfractured femur. Appendicular lean mass (aLM) was calculated as the sum of LM in arms and legs. We used two approaches to adjust aLM for body size: aLM divided by height squared (aLM/ht²), and aLM adjusted for height and FM (residuals). Both FM and aLM were significantly correlated with femoral BMD. However, the correlation coefficients for aLM were lower than for FM; they further decreased after adjustment for height squared, and were no longer significant after correction for both height and FM (residuals). When FM, aLM/ht², age, and time spent between fracture occurrence and DXA assessment were included together as the independent variables in a regression model, FM was the only independent variable significantly associated with BMD. The coefficients of partial correlation ranged from 0.414 to 0.647 depending on the femoral region of BMD assessment (P < 0.001). FM, but not SMM emerged as a pivotal determinant of BMD in our sample of hip fracture women.     

Italian National Survey of Blood Donors: External Quality Assessment (EQA) of Syphilis Testing

The detection of syphilis among blood donors may reveal high-risk sexual behavior, which can go unreported at the time of donor selection and compromise the safety of the donated blood. In Italy, blood is collected, tested, and distributed by transfusion services (TSs), which also perform outpatient transfusions. Although the TSs must screen for syphilis by law, there are no indications of the specific type of method to be used, generating discrepancies in the results obtained by the different TSs. To determine the proficiency of the TSs in screening for syphilis, we performed an external quality assessment (EQA). The EQA was based on two shipments of serum panels; 133 and 118 of the 326 existing TSs participated in the first and second shipments, respectively. Each panel consisted of both positive and negative serum samples. The results confirmed that the use of a single nontreponemal test (the Venereal Disease Research Laboratory [VDRL] and the rapid plasma reagin [RPR] tests) is the least sensitive means of identifying samples that are positive for syphilis antibodies. We also found that the interpretation of the results of manual techniques, such as the RPR test, the VDRL test, the Treponema pallidum hemagglutination (TPHA) assay, and the T. pallidum particle agglutination (TPPA) assay, can vary greatly among different TSs and operators. Total Ig enzyme immunoassays (EIAs) are the most sensitive. However, the determination of syphilis on the basis of the results of a single test is not sufficient for an accurate screening; and all blood units should thus be assessed by two distinct treponemal tests, that is, a total Ig EIA and the TPHA or the TPPA assay.Syphilis is a reemerging disease and is caused by the spirochete Treponema pallidum. In most cases it is sexually transmitted, although it can also be transmitted from mother to child in utero and, rarely, through blood transfusion, especially through the transfusion of fresh blood components (6, 12). Serological tests for syphilis are considered to be a milestone in syphilis control, and since as early as the 1930s they have greatly contributed to the detection of T. pallidum infection not only in the clinical setting but also in transfusional medicine. The detection of blood donors who are positive for syphilis is an important public health concern, given that testing may reveal high-risk sexual behavior, which can go unreported at the time of donor selection and compromise the safety of blood used for transfusions.In some European countries, the occurrence of T. pallidum infection in the general population has been increasing, and this increase is reflected in its growing occurrence among blood donors. In particular, a survey performed in England has indicated that since 2001 there has been a trend toward a moderate increase in the incidence of T. pallidum infection among blood donors (2). In Germany, although the incidence of infection among donors is very low, increases have been recorded since 1991 (9). The incidence of T. pallidum infection among blood donors is also increasing in Italy. In particular, according to the Transfusion Transmitted Infections Surveillance System (7), it increased from 3.8 per 100,000 donations in 1999 to 7 per 100,000 donations in 2006 (11).The data collected by the Transfusion Transmitted Infections Surveillance System in Italy are provided by the existing 326 transfusion services (TSs). These are hospital-based facilities where blood is collected, tested, and distributed and where, in most cases, outpatient transfusions are performed (10). In 2006, there were 1,539,454 donors, for a total of 2,402,267 donated units. Remarkably, 85% of the donors provided multiple donations (4). Although the TSs are required by law to screen for syphilis, there are no indications of the specific type of method that must be used, nor is there any confirmatory algorithm for testing on the basis of the different assays available. In fact, the laboratory assessment of syphilis is generally based on the detection of antibodies against T. pallidum antigens in blood by the use of either specific or nonspecific reagents. Methods based on the detection of specific Treponema antigens include passive agglutination, such as the T. pallidum hemagglutination (TPHA) assay or the T. pallidum particle agglutination (TPPA) assay, and indirect immunofluorescence, such as the fluorescent treponemal antibody absorbed (FTA-ABS) assay or the most sensitive assay, the enzyme immunoassay (EIA), for the detection of specific IgG and IgM or total Ig. Additional methods are based on nonspecific reagents, including nontreponemal lipid antigens (cardiolipin), and they most commonly rely on the flocculation technique. Of these, the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests are the most commonly used.The use of different assays from such a large array could generate discrepancies in the detection of syphilis among TSs, stressing the need for quality assessment. To this end, we performed an external quality assessment (EQA) of the quality and the comparability of the results obtained by the different TSs with the aim of contributing to the development of preventive and corrective measures (1, 3).     

Muscle mass and functional recovery in women with hip fracture

OBJECTIVE: To investigate the association between muscle mass and functional recovery in women with hip fracture. DESIGN: A total of 200 of 230 women with hip fracture admitted consecutively to a rehabilitation hospital were investigated in this survey study. Lean mass (LM) was assessed by dual-energy x-ray absorptiometry, 23.1 +/- 7.9 (mean +/- SD) days after fracture occurrence. Appendicular LM (aLM) was calculated as the sum of LM in arms and legs. Because metal implants (prostheses and nails) affect the regional assessment of body composition, aLM was corrected by substituting LM in the unfractured leg for LM in the fractured leg: corrected aLM = (LM in unfractured leg x 2) + LM in arms. We used two approaches to adjust corrected aLM for body size: corrected aLM divided by height squared (aLM/ht), and corrected aLM adjusted for height and fat mass (residuals). Functional recovery was assessed by using Barthel index scores. RESULTS: After adjustment for body size, corrected aLM was neither significantly correlated with Barthel index scores nor with the change in Barthel index scores after rehabilitation. Also, after stratification for quintiles of aLM/ht and residuals, no significant differences in functional recovery were found among the five groups. CONCLUSIONS: LM assessed after hip fracture is not associated with functional outcome in women.     

From Trials to a Real Hospital Setting: Effectiveness of Pegylated Interferon-α-2b/Ribavirin Combination Therapy for Naïve Chronic Hepatitis C Patients

Registration trials regarding pegylated interferon treatment of hepatitis C have created great expectations for improved results, but there is little information on actual outcomes in everyday hospital practice. We aimed to define the effectiveness of this treatment in a hospital setting. Seventy-four naïve patients with hepatitis C treated with 12 kD-pegylated-interferon-α-2-b/ribavirin (PEG-IFN) were retrospectively analyzed in comparison with 54 patients treated with IFN-α-2-b/ribavirin (STANDARD IFN) and with results of three main registration trials. Overall sustained viral response rates were 46% in the STANDARD IFN group and 54% in PEG-IFN group, ranging from 48–61% in similar arms of the registration trials considered, although more of our patients presented comorbidity and high-grade fibrosis, and our dosages at outset of PEG-IFN were lower than optimal (mean 1.18 μg/kg BW). In our hospital setting, the effectiveness of PEG-IFN/ribavirin therapy appeared similar to that reported in large registration trials.     

In vivo visualization of gold-loaded cells in mice using x-ray computed tomography

The ability to perform cell tracking using x-ray computed tomography combined with gold nanoparticles has been demonstrated recently on ex vivo samples using different malignant and nonmalignant cell lines. Here we proved the concept of the method for in vivo assessment in a small-animal model of malignant brain tumors. The limitations of the method due to radiation dose constraints were investigated using Monte Carlo simulations. Taking into consideration different x-ray entrance doses and the spatial resolution, the visibility of the cell clusters was evaluated. The results of the experiments conducted on mice implanted with F98 tumor cells confirmed the prediction of the Monte Carlo calculations. Small clusters of cells exogenously loaded with gold nanoparticles could be visualized using our in vivo method.From the Clinical EditorThis article discusses the use of CT-based detection of gold nanoparticle loaded cells of interest in small-animal models of malignant brain tumors, where small clusters of cells loaded with gold nanoparticles could be visualized.     

Cough reflex responses during pulmonary C-fibre receptor activation in anesthetized rabbits

We investigated the changes induced by pulmonary C-fibre receptor activation in the cough reflex evoked by mechanical stimulation of the tracheobronchial tree in pentobarbitone anesthetized, spontaneously breathing rabbits. Phrenic nerve and abdominal muscle activities were monitored along with tracheal and arterial blood pressures. The activation of pulmonary C-fibre receptors by means of right atrial injection of phenylbiguanide (PBG) caused the pulmonary chemoreflex characterized by tachypnea, bradycardia and hypotension. During the pulmonary chemoreflex, the time components (total cycle duration, inspiratory and expiratory times) of the cough motor pattern significantly decreased, whereas no consistent changes in peak phrenic and abdominal activity, peak tracheal pressure and number of coughs evoked by each stimulation trial were observed. At variance with previous findings in cats and dogs, the results show that tracheobronchial cough is not significantly reduced in the rabbit during PBG-induced chemoreflex. This study is the first to provide evidence supporting the hypothesis that the time components of the cough motor pattern are, to some extent, dependent upon the timing characteristics of the ongoing respiratory activity and suggests a novel mechanism leading to cough depression.     

Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in In Vitro Models Simulating Metastatic Calcification

Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro‐calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS‐stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS‐stimulated fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment‐dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro‐calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co‐localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the in vitro models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic‐like conditions could trigger valve calcification per se, with LPS and allogenic macrophage‐derived secretory products acting as possible calcific enhancers via inflammatory responses. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.