Impact of maternal social vulnerability and timing of prenatal care on outcome of prenatally detected congenital heart disease.

OBJECTIVES: Early prenatal detection of congenital heart disease (CHD) allows mothers to plan for their pregnancy and delivery; however, the effect of certain sociodemographic and fetal factors on prenatal care has not been investigated thoroughly. This study evaluated the impact of maternal and fetal characteristics on the timing of prenatal diagnosis of CHD and fetal and postnatal outcomes. METHODS: This retrospective multicenter cohort study included women with a fetal echocardiographic diagnosis of CHD between 2010 and 2019. Women were grouped into quartiles of social vulnerability (quartiles 1-4; low-high) using the 2014 social vulnerability index (SVI) provided by the Centers for Disease Control and Prevention. A fetal disease severity score (range, 1-7) was calculated based on a combination of CHD severity (mild = 1; moderate = 2; severe, two ventricles = 3; severe, single ventricle = 4 points) and prenatally diagnosed genetic abnormality, non-cardiac abnormality and fetal hydrops (1 point each). Late diagnosis was defined as a fetal echocardiographic diagnosis of CHD after 24 weeks' gestation. Univariate and multivariable regression analyses were used to identify factors associated with late diagnosis, termination of pregnancy (TOP), postnatal death, prenatal-postnatal discordance in CHD diagnosis and severity and, for liveborn infants, to identify which prenatal variables were associated with postnatal death or heart transplant. RESULTS: Among 441 pregnancies included, 94 (21%) had a late diagnosis of CHD. Late diagnosis was more common in the most socially vulnerable quartile, 38% of women in this group having diagnosis > 24 weeks, compared with 14-18% in the other three quartile groups. Late diagnosis was also associated with Catholic or other Christian religion vs non-denominational or other religion and with a lower fetal disease severity score. There were 93 (21%) TOP and 26 (6%) in-utero fetal demises. Factors associated with TOP included early diagnosis and greater fetal disease severity. Compared with the other quartiles, the most socially vulnerable quartile had a higher incidence of in-utero fetal demise and a lower incidence of TOP. Among the 322 liveborn infants, 49 (15%) died or underwent heart transplant during the follow-up period (range, 0-16 months). Factors associated with postnatal death or heart transplant included longer delay between obstetric ultrasound examination at which CHD was first suspected and fetal echocardiogram at which CHD was confirmed and greater fetal disease severity. CONCLUSIONS: High social vulnerability, Catholic or other Christian religion and low fetal disease severity are associated with late prenatal CHD diagnosis. Delays in CHD diagnosis are associated with fewer TOPs and worse postnatal outcome. Therefore, efforts to expedite fetal echocardiography following abnormal obstetric screening, particularly for at-risk women (e.g. those with high SVI), have the potential to impact pregnancy and postnatal outcome among the prenatally diagnosed CHD population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Particulate matter chemical component concentrations and sources in settings of household solid fuel use.

Particulate matter (PM) air pollution derives from combustion and non-combustion sources and consists of various chemical species that may differentially impact human health and climate. Previous reviews of PM chemical component concentrations and sources focus on high-income urban settings, which likely differ from the low- and middle-income settings where solid fuel (ie, coal, biomass) is commonly burned for cooking and heating. We aimed to summarize the concentrations of PM chemical components and their contributing sources in settings where solid fuel is burned. We searched the literature for studies that reported PM component concentrations from homes, personal exposures, and direct stove emissions under uncontrolled, real-world conditions. We calculated weighted mean daily concentrations for select PM components and compared sources of PM determined by source apportionment. Our search criteria yielded 48 studies conducted in 12 countries. Weighted mean daily cooking area concentrations of elemental carbon, organic carbon, and benzo(a)pyrene were 18.8 µg m-3 , 74.0 µg m-3 , and 155 ng m-3 , respectively. Solid fuel combustion explained 29%-48% of principal component/factor analysis variance and 41%-87% of PM mass determined by positive matrix factorization. Multiple indoor and outdoor sources impacted PM concentrations and composition in these settings, including solid fuel burning, mobile emissions, dust, and solid waste burning.

The impact of biogas and fuelwood use on institutional kitchen air quality in Kampala, Uganda.

Experts have suggested that microscale biogas systems offer a source of renewable energy that improves indoor air quality, but such impacts have not been directly measured. This study documented cooking behaviors and measured 2.5-µm particulate matter (PM2.5 ), carbon monoxide (CO), and sulfur dioxide (SO2 ) concentrations within 14 institutional kitchens in Kampala, Uganda, that prepare meals using biogas (n=5), a mixture of biogas and fuelwood (n=3), and fuelwood (n=6). Small institutions (10-30 people) with biogas kitchens had 99% lower concentrations of PM2.5 (21 µg/m3 ) than fuelwood kitchens (3100 µg/m3 ). Larger institutions (>100 people) had biogas systems that produced insufficient gas and relied on fuelwood to meet over 90% of their energy needs. PM2.5 concentrations in these biogas-firewood kitchens were equivalent to concentrations in fuelwood kitchens. Although concentrations of hydrogen sulfide (H2 S) in biogas were as high as 2000 ppm, 75% of systems had undetectable H2 S levels (<100 ppm) in the biogas. Kitchens using biogas with high H2 S had correspondingly higher SO2 concentrations in the kitchen air. However, even the highest SO2 concentration in biogas kitchens (150 µg/m3 ) was lower than SO2 concentration in fuelwood kitchens (390 µg/m3 ). The results suggest that biogas systems can offer air quality improvements if sized properly for energy demands.

The discoloration of the Taj Mahal due to particulate carbon and dust deposition.

The white marble domes of the Taj Mahal are iconic images of India that attract millions of visitors every year. Over the past several decades the outer marble surfaces of the Taj Mahal have begun to discolor with time and must be painstakingly cleaned every several years. Although it has been generally believed that the discoloration is in some way linked with poor air quality in the Agra region, the specific components of air pollution responsible have yet to be identified. With this in mind, ambient particulate matter (PM) samples were collected over a one-year period and found to contain relatively high concentrations of light absorbing particles that could potentially discolor the Taj Mahal marble surfaces, that include black carbon (BC), light absorbing organic carbon (brown carbon, BrC), and dust. Analyses of particles deposited to marble surrogate surfaces at the Taj Mahal indicate that a large fraction of the outer Taj Mahal surfaces are covered with particles that contain both carbonaceous components and dust. We have developed a novel approach that estimates the impact of these deposited particles on the visible light surface reflectance, which is in turn used to estimate the perceived color by the human eye. Results indicate that deposited light absorbing dust and carbonaceous particles (both BC and BrC from the combustion of fossil fuels and biomass) are responsible for the surface discoloration of the Taj Mahal. Overall, the results suggest that the deposition of light absorbing particulate matter in regions of high aerosol loading are not only influencing cultural heritage but also the aesthetics of both natural and urban surfaces.

[Therapy of functional abdominal pain in childhood. Concept, acceptance and preliminary results of a short hypnotherapeutic-behavioural intervention]. / Therapie funktioneller Bauchschmerzen bei Kindern. Konzept, Akzeptanz und erste Pilotergebnisse einer hypnotherapeutisch-behavioralen Kurzintervention.

OBJECTIVE: Recurrent abdominal pain is one of the most frequent pain syndromes in childhood and is accompanied by notable functional impairment and unfavourable long-term outcome. Psychotherapeutic approaches are promising, but not widely used in Germany. The concept of a multimodal short-term intervention and its acceptance are described and preliminary results are reported. METHOD: A total of 21 children aged 6-12 years and their parents participated in a hypnotherapeutic-behavioural short intervention program. Preliminary results on efficacy up to 3 months are reported. RESULTS: Participating children showed a decrease in pain frequency and daily impairment. Health-related quality of life also increased and associated mental problems could be reduced. Content and conditions of the intervention were rated as helpful by children and parents. CONCLUSION: Preliminary results indicate that even short psychotherapeutic interventions might help affected children effectively and lower the burden felt by parents. Further investigations using a randomized controlled trial design and focussing on children suffering more severely should follow to allow major conclusions.

Patterns and predictors of personal exposure to indoor air pollution from biomass combustion among women and children in rural China.

UNLABELLED: Indoor air pollution (IAP) from domestic biomass combustion is an important health risk factor, yet direct measurements of personal IAP exposure are scarce. We measured 24-h integrated gravimetric exposure to particles < 2.5 µm in aerodynamic diameter (particulate matter, PM2.5) in 280 adult women and 240 children in rural Yunnan, China. We also measured indoor PM2.5 concentrations in a random sample of 44 kitchens. The geometric mean winter PM2.5 exposure among adult women was twice that of summer exposure [117 µg/m³ (95% CI: 107, 128) vs. 55 µg/m³ (95% CI: 49, 62)]. Children's geometric mean exposure in summer was 53 µg/m³ (95% CI: 46, 61). Indoor PM2.5 concentrations were moderately correlated with women's personal exposure (r=0.58), but not for children. Ventilation during cooking, cookstove maintenance, and kitchen structure were significant predictors of personal PM2.5 exposure among women primarily cooking with biomass. These findings can be used to develop exposure assessment models for future epidemiologic research and inform interventions and policies aimed at reducing IAP exposure. PRACTICAL IMPLICATIONS: Our results suggest that reducing overall PM pollution exposure in this population may be best achieved by reducing winter exposure. Behavioral interventions such as increasing ventilation during cooking or encouraging stove cleaning and maintenance may help achieve these reductions.

Reconsidering statistical methods for assessing replication.

Recent empirical evaluations of replication in psychology have reported startlingly few successful replication attempts. At the same time, these programs have noted that the proper way to analyze replication studies is far from a settled matter and have analyzed their data in several different ways. This presents 2 challenges to interpreting the results of these programs. First, different analysis methods assess different operational definitions of replication. Second, the properties of these methods are not necessarily common knowledge; it is possible for a successful replication to be deemed a failure by nearly all of the metrics used, and it is not always immediately clear how likely such errors are to occur. In this article, we describe the methods commonly used in replication research and how they imply specific operational definitions of replication. We then compute the probability of false failure (i.e., a successful replication is concluded to have failed) and false success determinations. These are shown to be high (often over 50%) and in many cases uncontrolled. We then demonstrate that errors are probable in the data to which these methods have been applied in the literature. We show that the probability that some reported conclusions about replication are incorrect can be as high as 75-80%. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Experimental demonstration of accurate Bragg peak localization with ionoacoustic tandem phase detection (iTPD).

Accurate knowledge of the exact stopping location of ions inside the patient would allow full exploitation of their ballistic properties for patient treatment. The localized energy deposition of a pulsed particle beam induces a rapid temperature increase of the irradiated volume and leads to the emission of ionoacoustic (IA) waves. Detecting the time-of-flight (ToF) of the IA wave allows inferring information on the Bragg peak location and can henceforth be used forin-vivorange verification. A challenge for IA is the poor signal-to-noise ratio at clinically relevant doses and viable machines. We present a frequency-based measurement technique, labeled as ionoacoustic tandem phase detection (iTPD) utilizing lock-in amplifiers. The phase shift of the IA signal to a reference signal is measured to derive theToF. Experimental IA measurements with a 3.5 MHz lead zirconate titanate (PZT) transducer and lock-in amplifiers were performed in water using 22 MeV proton bursts. A digital iTPD was performedin-silicoat clinical dose levels on experimental data obtained from a clinical facility and secondly, on simulations emulating a heterogeneous geometry. For the experimental setup using 22 MeV protons, a localization accuracy and precision obtained through iTPD deviates from a time-based reference analysis by less than 15µm. Several methodological aspects were investigated experimentally in systematic manner. Lastly, iTPD was evaluatedin-silicofor clinical beam energies indicating that iTPD is in reach of sub-mm accuracy for fractionated doses < 5 Gy. iTPD can be used to accurately measure theToFof IA signals online via its phase shift in frequency domain. An application of iTPD to the clinical scenario using a single pulsed beam is feasible but requires further development to reach <1 Gy detection capabilities.

Organic compound characterization and source apportionment of indoor and outdoor quasi-ultrafine particulate matter in retirement homes of the Los Angeles Basin.

UNLABELLED: Quasi-ultrafine (quasi-UF) particulate matter (PM(0.25)) and its components were measured in indoor and outdoor environments at four retirement communities in Los Angeles Basin, California, as part of the Cardiovascular Health and Air Pollution Study (CHAPS). The present paper focuses on the characterization of the sources, organic constituents and indoor and outdoor relationships of quasi-UF PM. The average indoor/outdoor ratios of most of the measured polycyclic aromatic hydrocarbons (PAHs), hopanes, and steranes were close to or slightly lower than 1, and the corresponding indoor-outdoor correlation coefficients (R) were always positive and, for the most part, moderately strong (median R was 0.60 for PAHs and 0.74 for hopanes and steranes). This may reflect the possible impact of outdoor sources on indoor PAHs, hopanes, and steranes. Conversely, indoor n-alkanes and n-alkanoic acids were likely to be influenced by indoor sources. A chemical mass balance model was applied to both indoor and outdoor speciated chemical measurements of quasi-UF PM. Among all apportioned sources of both indoor and outdoor particles, vehicular emissions was the one contributing the most to the PM(0.25) mass concentration measured at all sites (24-47% on average). PRACTICAL IMPLICATIONS: Although people (particularly the elderly retirees of our study) generally spend most of their time indoors, a major portion of the PM(0.25) particles they are exposed to comes from outdoor mobile sources. This is important because, an earlier investigation, also conducted within the Cardiovascular Health and Air Pollution Study (CHAPS), showed that indoor-infiltrated particles from mobile sources are more strongly correlated with adverse health effects observed in the elderly subjects living in the studied retirement communities compared with other particles found indoors (Delfino et al., 2008).

[Impulse oscillometry in the diagnosis of the severity of obstructive pulmonary disease]. / Die Impulsoszillometrie in der Schweregraddiagnostik obstruktiver Lungenerkrankungen.

Impulse oscillometry (IOS) is a computer-supported method for the measurement of complex mechanical airway characteristics. The aim of this study was to evaluate the applicability of IOS in the diagnosis of obstructive airway diseases in comparison to the standard methods of spirometry, pneumotachymetry, and bodyplethysmography. 244 patients (age 61.5 +/- 13.6 years; 61 % men) with bronchial asthma (n = 65) and chronic obstructive pulmonary disease (COPD) (n = 179) were retrospectively analysed. By means of body plethysmography (Srtot < 120%pred) an obstruction was diagnosed in 94%, by pneumotachymetry (FEV1 < 80%pred) in 78 %, and by IOS depending on the parameter chosen in 87-94% of patients. Mild and medium obstructions could be identified by means of all IOS parameters except for R20: severe obstructions, however, were better detected by means of the frequency-dependent resistance FDR and reactance at 5 Hz, X5. The parameters R5, X5, and Zrs, however, showed a tendency to underestimate the degree of obstruction. Bronchial obstruction can reliably be diagnosed by IOS when, in cases of severe obstruction, more complex parameters like FDR and X5 are included. The parameters of the standard methods (body plethysmography and pneumotachymetry) show relatively low correlations due to the different measurement methods not only in comparison to IOS but also to one another. In summary, IOS is a convenient method for patients with a low dependency on cooperation for the evaluation of obstructive airway diseases complementary to the established standard methods and, in addition, is useful as a sensitive screening tool for the early detection of bronchial obstruction.

Deliberating performance targets workshop: Potential paths for emerging PM2.5 and O3 air sensor progress.

The United States Environmental Protection Agency held an international two-day workshop in June 2018 to deliberate possible performance targets for non-regulatory fine particulate matter (PM2.5) and ozone (O3) air sensors. The need for a workshop arose from the lack of any market-wide manufacturer requirement for Ozone documented sensor performance evaluations, the lack of any independent third party or government-based sensor performance certification program, and uncertainty among all users as to the general usability of air sensor data. A multi-sector subject matter expert panel was assembled to facilitate an open discussion on these issues with multiple stakeholders. This summary provides an overview of the workshop purpose, key findings from the deliberations, and considerations for future actions specific to sensors. Important findings concerning PM2.5 and O3 sensors included the lack of consistent performance indicators and statistical metrics as well as highly variable data quality requirements depending on the intended use. While the workshop did not attempt to yield consensus on any topic, a key message was that a number of possible future actions would be beneficial to all stakeholders regarding sensor technologies. These included documentation of best practices, sharing quality assurance results along with sensor data, and the development of a common performance target lexicon, performance targets, and test protocols.

Treatment of invasive pulmonary aspergillosis in neutropenic patients by additional bronchoscopic amphotericin B instillation.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy. OBJECTIVES: This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA. METHODS: Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan. RESULTS: The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients). CONCLUSIONS: Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

Sources, evolution and impacts of EC and OC in snow on sea ice: a measurement study in Barrow, Alaska.

Based on the field measurements in Barrow, Alaska within the period of April-May 2015, we investigate the sources and variations of elemental carbon (EC) and organic carbon (OC) in the surface layer of snowpack on sea ice, and estimate their effects on the sea ice albedo. Results show that the snow OC in Barrow are from natural sources (e.g. terrestrial higher plants and micro-organisms) mainly, as well as biomass burning (e.g. forest fires and straw combustion) as an important part. Both EC and OC can accumulate at the snow surface with snow melt. The variations in EC and OC and liquid water content in the snow layer are well consistent during the snow-melting period. A higher rate of snow melt implied a more efficient enrichment of EC and OC. In the last phase of snow melt, the concentration increased to a maximum of 16.2 ng/g for EC and 128 ng/g for OC, which is ∼10 times larger than those before snow melt onset. Except for the dominant influence of melt amplification mechanism, the variation in concentrations of EC and OC could be disturbed by the air temperature fluctuation and snowfall. Our study indicates that the light-absorbing impurities contributed 1.6%-5.1% to the reduction in sea ice albedo with melt during the measurement period. The significant period of light-absorbing impurities influencing on sea ice albedo begins with the rapid melting of overlying snow and ends before the melt ponds formed widely, which lasted for about 10 days in Barrow, 2015.

Atmospheric mercury speciation in Yellowstone National Park.

Atmospheric concentrations of elemental mercury (Hg(0)), reactive gaseous Hg (RGM), and particulate Hg (pHg) concentrations were measured in Yellowstone National Park (YNP), U.S.A. using high resolution, real time atmospheric mercury analyzers (Tekran 2537A, 1130, and 1135). A survey of Hg(0) concentrations at various locations within YNP showed that concentrations generally reflect global background concentrations of 1.5-2.0 ng m(-3), but a few specific locations associated with concentrated geothermal activity showed distinctly elevated Hg(0) concentrations (about 9.0 ng m(-3)). At the site of intensive study located centrally in YNP (Canyon Village), Hg(0) concentrations did not exceed 2.5 ng m(-3); concentrations of RGM were generally below detection limits of 0.88 pg m(-3) and never exceeded 5 pg m(-3). Concentrations of pHg ranged from below detection limits to close to 30 pg m(-3). RGM and pHg concentrations were not correlated with any criteria gases (SO(2), NO(x), O(3)); however pHg was weakly correlated with the concentration of atmospheric particles. We investigated three likely sources of Hg at the intensive monitoring site: numerous geothermal features scattered throughout YNP, re-suspended soils, and wildfires near or in YNP. We examined relationships between the chemical properties of aerosols (as measured using real time, single particle mass spectrometry; aerosol time-of-flight mass spectrometer; ATOFMS) and concentrations of atmospheric pHg. Based on the presence of particles with distinct chemical signatures of the wildfires, and the absence of signatures associated with the other sources, we concluded that wildfires in the park were the main source of aerosols and associated pHg to our sampling site.

Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine.

Bupivacaine, a local anesthetic and cationic amphiphile, forms stable liposomal-like structures upon direct mixing with plasmid DNA in aqueous solutions. These structures are on the order of 50-70 nm as determined by scanning electron microscopy, and are homogeneous populations as analyzed by density gradient centrifugation. The DNA within these structures is protected from nuclease degradation and UV-induced damage in vitro. Bupivacaine:DNA complexes have a negative zeta potential (surface charge), homogeneous nature, and an ability to rapidly assemble in aqueous solutions. Bupivacaine:DNA complexes, as well as similar complexes of DNA with other local anesthetics, have the potential to be a novel class of DNA delivery agents for gene therapy and DNA vaccines.

Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis.

OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found in high concentrations in pleural effusions. Because MMP and TIMP may play a part in the causation of the fibrosis seen in tuberculous (TB) pleuritis their occurrence was examined. DESIGN: Pleural effusion fluid and plasma concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA in 21 patients with TB pleuritis. To adjust for the total protein content, respective ratios were calculated. Activities of MMP-2 and MMP-9 were measured by gelatine zymography and the MMP-9/MMP-2 ratios calculated. Pleural effusions and plasma of 15 patients with congestive heat failure (CHF) and plasma of 15 healthy persons (CON) served as controls. RESULTS: Immunoreactive pleural fluid concentrations of MMP-1, MMP-2, MMP-8, and MMP-9 were higher in TB compared to CHF, but plasma concentrations were not different between the groups. TB pleural fluid concentrations of MMP-1, MMP-2, TIMP-1, and TIMP-2 were higher compared to TB plasma. MMP-3 was found in trace amounts only. The MMP-9/total protein ratios in pleural fluid were higher in TB compared to CHF (0.4492+/-0.1633 vs 0.0364+/-0.0145, P<0.005) but the TIMP-1 ratios were lower (139.0+/-28.7 vs 517.8+/-183.7, P<0.0005). In TB pleural fluid vs TB plasma, the respective MMP-1, MMP-2, TIMP-1, and TIMP-2 ratios were increased (0.46+/-0.10 vs 0.17+/-0.02; 25.2+/-2.8 vs 4.2+/-0.9; 139.0+/-28.7 vs 27.8+/-8.2; 0.67+/-0.13 vs 0.18+/-0.04, P<0.0005 each). Gelatine zymography demonstrated MMP-2 and MMP-9 bands of different brightness in TB effusions but in CHF effusions the MMP-9 band was barely visible. The MMP-9/MMP-2 effusion ratios were therefore higher in TB compared to CHF (0.46+/-0.15 vs 0.05+/-0.04, P<0.0005). CONCLUSION: Compartmentalized MMP-1, MMP-2, TIMP-1, and TIMP-2 and, compared to CHF, a surplus of MMP-1, MMP-2, MMP-8, and MMP-9 in the pleural space obviously contribute to the fibrotic reactions in TB pleuritis.

Usefulness of a branching treadmill protocol for evaluation of cardiac functional capacity.

A branching treadmill protocol was designed to measure functional capacity in patients with low work capacity and varying ability to walk at speeds used in traditional protocols. A comfortable walking pace is first selected (2.0 to 3.5 mph, 0.25 mph increments) and the workload is then increased every 2 minutes in 1 MET increments (a multiple of the resting oxygen uptake [1 MET = 3.5 ml O2/kg/min]) by adjusting grade. Nine trained (maximal MET = 7.6 +/- 1.6, mean +/- standard deviation) male subjects (age 59 +/- 7 years) with previous myocardial infarction and 9 trained (maximal MET = 11.7 +/- 2.5) male control subjects (age 56 +/- 8 years) completed submaximal and maximal workloads without handrail support. The measured oxygen consumption, volume of oxygen in ml/kg/min (VO2), was compared with the predicted VO2 cost of treadmill walking calculated from speed and grade. A linear regression analysis of predicted versus measured VO2 was performed. There were no significant differences between myocardial infarction and control regression lines. Therefore, a simplified prediction equation for estimated VO2 in myocardial infarction and control subjects is proposed. Overall VO2 prediction = 1.61 + 0.99 x. The main advantage of the branching protocol format is the selection of a stable, brisk walking pace compatible with age and gait, which may improve mechanical efficiency through impedance matching. The protocol is adaptable enough in design so that most patients can complete the exercise test without use of handrails, which is essential for an accurate estimate of VO2 from treadmill speed and grade.

The effect of corticotropin-releasing hormone (CRH) on the adrenal medulla in hypophysectomized rats.

CRH occurs in the adrenal medulla of rats. We were interested to know whether CRH affects meduallary chromaffin cells in the absence of ACTH. We investigated the morphological changes of the adrenal medulla in Sprague Dawley rats with light and electron microscopy in normal rats, hypophysectomized rats, and hypophysectomized rats following injections of CRH (10 micrograms = 3 nmol for three days). Chromaffin cells were characterized by immunohistochemistry (anti-tyrosine hydroxylase). At light microscopy level chromaffin cells of hypophysectomized rats were reduced in number. On electron microscopy the number of granules and cell organelles were decreased. Following injections of CRH the medulla regained a more compact texture with cell organelles homogenously distributed, but with chromaffin granules still being reduced in number. Immunohistochemistry allowed the identification of chromaffin cells located within the adrenal cortex. In hypophysectomized rats these cells showed fewer signs of alterations compared to cells located within the medulla itself and had recovered better after treatment with CRH. In conclusion, CRH seems to exert a trophic effect on chromaffin cells in the absence of pituitary ACTH. This observation may provide further evidence for a close interaction of the two neuroendocrine stress systems.

Carnitine supplementation and depletion: tissue carnitines and enzymes in fatty acid oxidation.

Sixty-two male rats were randomly assigned into a 3 X 2 X 2 factorial design containing 12 groups according to carnitine treatment, exercise training (treadmill, 1 h, 5 times/wk, 8 wk, 26.8 m/min, 15% grade), and physical activity [rested for 60 h before they were killed or with an acute bout of exercise (1 h, 26.8 m/min, 15% grade) immediately before they were killed]. Isotonic saline was injected intraperitoneally 5 times/wk in the controls, whereas 750 mg/kg of L- or D-carnitine, respectively, were injected in the supplemented and depleted treatment groups. A significant increase in free and short-chain acyl carnitine concentration in skeletal muscle and heart was observed in L-carnitine supplemented rats, whereas a significant reduction in skeletal muscle, heart, and liver occurred in rats depleted of L-carnitine. Long-chain acyl carnitine in all tissues was not altered by carnitine treatment; training increased plasma and liver concentrations, whereas acute exercise decreased skeletal muscle and increased liver concentrations. An acute bout of exercise significantly increased short-chain acylcarnitine in liver, regardless of carnitine and/or training effects. beta-Hydroxyacyl-CoA dehydrogenase activity in skeletal muscle was induced by training but reduced by depletion. Carnitine acetyltransferase (CAT) was significantly increased in heart by L-carnitine supplementation, whereas it was reduced by depletion in skeletal muscle. Exercise training significantly increased CAT activity in skeletal muscle but not in heart, whereas acute exercise significantly increased activity in both tissues. Carnitine palmitoyltransferase activity was increased by acute exercise in the heart in only the supplemented and exercise-trained rats.

BALF N-acetylglucosaminidase and beta-galactosidase activities in idiopathic pulmonary fibrosis.

The lysosomal enzymes N-acetylglucosaminidase (N-ACGA) and beta-galactosidase (beta-gal) are involved in cellular collagen metabolism and may, therefore, be markers of fibrosis in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis (IPF). N-ACGA and beta-gal were analyzed in the bronchoalveolar lavage fluid (BALF) of patients with the histologic pattern of usual interstitial pneumonia (UIP, n=10) and controls (n=9). Cellular distribution in BALF as well as the concentration of TGF-beta a well-known mediator of fibroblast matrix deposition were correlated to the enzyme activities in both groups of patients. We found that both, N-ACGA (UIP: 25.2 nmol/l s +/- 3.4; controls: 73 nmol/l s +/- 1.3) and beta-gal (UIP: 4.7 nmol/l s +/- 0.5; controls: 2.4 nmol/l s +/- 0.3) were elevated significantly in BALF of patients with IPF compared to that of control patients (P<0.003). This increase was paralleled by an increase in neutrophils (IPF: 17.9% +/- 21.8; controls: 5.4% +/- 6.3; P=0.03) and eosinophils (IPF: 2.0% +/- 1.5; controls: 0.2% +/- 0.45; P=0.002) in BALF fluid. In addition, N-ACGA activity correlated closely with lung function (FVC, TLC, and DLCO), transforming growth factor-beta (TGF-beta) in BALF (r=0.77, P=0.008) and activated lymphocytes (r=0.66, P=0.0021). Our findings suggest that measurement of lysosomal enzymes such as N-ACGA may represent a useful indicator of fibrotic activity in IPF.