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Background: Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings., Methods: This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine., Results: No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers ( p  < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella , Faecalibacterium , Sutterella , and Bacterioides . At 34 weeks, there were lower abundances of Magasphaera , Phascolarctobacterium , and Turicibacter and higher abundances of Bacteriodes , and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance., Conclusion: Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ruebel, Gilley, Yeruva, Tang, Frank, Garcés, Figueroa, Lan, Assress, Kemp, Westcott, Hambidge, Shankar and Krebs.)

Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more "odd-chain" long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues., Competing Interests: Conflict of interest S. H. A. is founder and principal of XenoMed, LLC (dba XenoMet), which is focused on research and discovery in the area of microbial metabolism. XenoMed had no part in the research design, funding, results, or writing of the manuscript. S. H. A. and J. D. are coinventors on a patent application in the area of cyclopropane fatty acids., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Untargeted metabolomics is an analytical approach with numerous applications serving as an effective metabolic phenotyping platform to characterize small molecules within a biological system. Data quality can be challenging to evaluate and demonstrate in metabolomics experiments. This has driven the use of pooled quality control (QC) samples for monitoring and, if necessary, correcting for analytical variance introduced during sample preparation and data acquisition stages. Described herein is a scoping literature review detailing the use of pooled QC samples in published untargeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics studies. A literature query was performed, the list of papers was filtered, and suitable articles were randomly sampled. In total, 109 papers were each reviewed by at least five reviewers, answering predefined questions surrounding the use of pooled quality control samples. The results of the review indicate that use of pooled QC samples has been relatively widely adopted by the metabolomics community and that it is used at a similar frequency across biological taxa and sample types in both small- and large-scale studies. However, while many studies generated and analyzed pooled QC samples, relatively few reported the use of pooled QC samples to improve data quality. This demonstrates a clear opportunity for the field to more frequently utilize pooled QC samples for quality reporting, feature filtering, analytical drift correction, and metabolite annotation. Additionally, our survey approach enabled us to assess the ambiguity in the reporting of the methods used to describe the generation and use of pooled QC samples. This analysis indicates that many details of the QC framework are missing or unclear, limiting the reader's ability to determine which QC steps have been taken. Collectively, these results capture the current state of pooled QC sample usage and highlight existing strengths and deficiencies as they are applied in untargeted LC-MS metabolomics.

Optimization of mass spectrometric parameters for a data dependent acquisition (DDA) experiment is essential to increase the MS/MS coverage and hence increase metabolite identifications in untargeted metabolomics. We explored the influence of mass spectrometric parameters including mass resolution, radio frequency (RF) level, signal intensity threshold, number of MS/MS events, cycle time, collision energy, maximum ion injection time (MIT), dynamic exclusion, and automatic gain control (AGC) target value on metabolite annotations on an Exploris 480-Orbitrap mass spectrometer. Optimal annotation results were obtained by performing ten data dependent MS/MS scans with a mass isolation window of 2.0 m / z and a minimum signal intensity threshold of 1 × 10 4 at a mass resolution of 180,000 for MS and 30,000 for MS/MS, while maintaining the RF level at 70%. Furthermore, combining an AGC target value of 5 × 10 6 and MIT of 100 ms for MS and an AGC target value of 1 × 10 5 and an MIT of 50 ms for MS/MS scans provided an improved number of annotated metabolites. A 10 s exclusion duration and a two stepped collision energy were optimal for higher spectral quality. These findings confirm that MS parameters do influence metabolomics results, and propose strategies for increasing metabolite coverage in untargeted metabolomics. A limitation of this work is that our parameters were only optimized for one RPLC method on single matrix and may be different for other protocols. Additionally, no metabolites were identified at level 1 confidence. The results presented here are based on metabolite annotations and need to be validated with authentic standards.

Background: Maternal obesity is an important determinant of offspring obesity risk, which may be mediated via changes in the infant microbiome., Objectives: We examined infant faecal microbiome, short-chain fatty acids (SCFA), and maternal human milk oligosaccharides (HMO) in mothers with overweight/obese body mass index (BMI) (OW) compared with normal weight (NW) (Clinicaltrials.gov NCT01131117)., Methods: Infant stool samples at 1, 6, and 12 months were analysed by 16S rRNA sequencing. Maternal (BODPOD) and infant (quantitative nuclear magnetic resonance [QMR]) adiposity were measured. HMOs at 2 months postpartum and faecal SCFAs at 1 month were also assessed. Statistical analyses included multivariable and mixed linear models for assessment of microbiome diversity, composition, and associations of taxonomic abundance with metabolic and anthropometric variables., Results: At 1 month, offspring of women with obesity had lower abundance of SCFA-producing bacteria (including Ruminococcus and Turicibacter) and lower faecal butyric acid levels. Lachnospiraceae abundance was lower in OW group at 6 months, and infant fat mass was negatively associated with the levels of Sutterella. Gradient boosting machine models indicated that higher α-diversity and specific microbial taxa at 1 month predicted elevated adiposity at 12 months with overall accuracy of 76.5%. Associations between maternal HMO concentrations and infant bacterial taxa differed between NW and OW groups., Conclusions: Elevated maternal BMI is associated with relative depletion of butyrate-producing microbes and faecal butyrate in the early infant faecal microbiome. Overall microbial richness may aid in prediction of elevated adiposity in later infancy., (© 2022 World Obesity Federation.)

The gut microbiota plays a critical role in energy homeostasis and its dysbiosis is associated with obesity. Maternal high-fat diet (HFD) and β-adrenergic stimuli alter the gut microbiota independently; however, their collective regulation is not clear. To investigate the combined effect of these factors on offspring microbiota, 20-week-old offspring from control diet (17% fat)- or HFD (45% fat)-fed dams received an injection of either vehicle or β3-adrenergic agonist CL316,243 (CL) for 7 days and then cecal contents were collected for bacterial community profiling. In a follow-up study, a separate group of mice were exposed to either 8 °C or 30 °C temperature for 7 days and blood serum and cecal contents were used for metabolome profiling. Both maternal diet and CL modulated the gut bacterial community structure and predicted functional profiles. Particularly, maternal HFD and CL increased the Firmicutes/Bacteroidetes ratio. In mice exposed to different temperatures, the metabolome profiles clustered by treatment in both the cecum and serum. Identified metabolites were enriched in sphingolipid and amino acid metabolism in the cecum and in lipid and energy metabolism in the serum. In summary, maternal HFD altered offspring's response to CL and altered microbial composition and function. An independent experiment supported the effect of thermogenic challenge on the bacterial function through metabolome change.

Pregnancy is proposed to aggravate cyst progression in autosomal dominant polycystic kidney disease (ADPKD) but Tolvaptan, the only FDA-approved drug for adult ADPKD, is not recommended for pregnant ADPKD patients because of potential fetal harm. Since pregnancy itself may increase the risk for ADPKD progression, we investigated the safety and efficacy of Elamipretide, a mitochondrial-protective tetrapeptide. Elamipretide was found to ameliorate the progression of kidney disease in pregnant Pkd1 RC/RC mice, in parallel with attenuation of ERK1/2 phosphorylation and improvement of mitochondrial supercomplex formation. Furthermore, Elamipretide was found to pass through the placenta and breast milk and ameliorate aggressive infantile polycystic kidney disease without any observed teratogenic or harmful effect. Elamipretide has an excellent safety profile and is currently tested in multiple phase II and phase III clinical trials. These preclinical studies support a potential clinical trial of Elamipretide for the treatment of ADPKD, particularly for patients that cannot take Tolvaptan., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the effect of exercise during pregnancy in sedentary women with obesity on longitudinal changes in long-chain acylcarnitine (LC-AC) concentrations. We hypothesized that exercise training would significantly decrease circulating LC-ACs throughout gestation compared with a nonexercise control group. Pregnant women with obesity considered otherwise healthy [ n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m 2 ] were randomized into an exercise ( n = 40, aerobic/resistance 3 times/wk, ∼13th gestation week until birth) or a nonexercise control ( n = 40) group. At gestation week 12.2 ± 0.5 and 36.0 ± 0.4, a submaximal exercise test was conducted, and indirect calorimetry was used to measure relative resting energy expenditure (REE), as well as respiratory exchange ratio (RER) at rest. Fasting blood samples were collected and analyzed for LC-AC concentrations. Fitness improved with prenatal exercise training; however, exercise training did not affect circulating LC-AC. When groups were collapsed, LC-ACs decreased during gestation (combined groups, P < 0.001), whereas REE (kcal/kg/day, P = 0.008) increased. However, average REE relative to fat-free mass (FFM) (kcal/kg FFM/day) and RER did not change. There was an inverse relationship between the change in RER and all LC-ACs (except C18:2) throughout gestation (C14: r = -0.26, P = 0.04; C16: r = -0.27, P = 0.03; C18:1: r = -0.28, P = 0.02). In summary, a moderate-intensity exercise intervention during pregnancy in women with obesity did not alter LC-ACs concentrations versus control, indicating that the balance between long-chain fatty acid availability and oxidation neither improved nor worsened with an exercise intervention. NEW & NOTEWORTHY This research showed that a moderate-intensity prenatal exercise program, consisting of aerobic and resistance training, did not negatively impact normal alterations in substrate supply and demand for the mother and the offspring throughout gestation. Findings provide support for metabolic safety of exercise during pregnancy.

Microtubule targeting agents (MTAs) have been used for the treatment of cancer for many decades and are among the most successful chemotherapeutic agents. However, their application and effectiveness are limited because of toxicity and resistance as well as a lack of knowledge of molecular mechanisms downstream of microtubule inhibition. Insights into key pathways that link microtubule disruption to cell death is critical for optimal use of these drugs, for defining biomarkers useful in patient stratification, and for informed design of drug combinations. Although MTAs characteristically induce death in mitosis, microtubule destabilizing agents such as vincristine also induce death directly in G1 phase in primary acute lymphoblastic leukemia (ALL) cells. Because many signaling pathways regulating cell survival and death involve changes in protein expression and phosphorylation, we undertook a comprehensive quantitative proteomic study of G1 phase ALL cells treated with vincristine. The results revealed distinct alterations associated with c-Jun N-terminal kinase signaling, anti-proliferative signaling, the DNA damage response, and cytoskeletal remodeling. Signals specifically associated with cell death were identified by pre-treatment with the CDK4/6 inhibitor palbociclib, which caused G1 arrest and precluded death induction. These results provide insights into signaling mechanisms regulating cellular responses to microtubule inhibition and provide a foundation for a better understanding of the clinical mechanisms of MTAs and for the design of novel drug combinations. The mass spectrometry proteomics data have been deposited to the PRIDE Archive (http://www.ebi.ac.uk/pride/archive/) via the PRIDE partner repository with the data set identifier PXD027190 and 10.6019/PXD027190., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Quantitative proteomics generates large datasets with increasing depth and quantitative information. With the advance of mass spectrometry and increasingly larger data sets, streamlined methodologies and tools for analysis and visualization of phosphoproteomics are needed both at the protein and modified peptide levels. To assist in addressing this need, we developed ProteoViz, which includes a set of R scripts that perform normalization and differential expression analysis of both the proteins and enriched phosphorylated peptides, and identify sequence motifs, kinases, and gene set enrichment pathways. The tool generates interactive visualization plots that allow users to interact with the phosphoproteomics results and quickly identify proteins and phosphorylated peptides of interest for their biological study. The tool also links significant phosphosites with sequence motifs and pathways that will help explain the experimental conditions and guide future experiments. Here, we present the workflow and demonstrate its functionality by analyzing a phosphoproteomic data set from two lymphoma cell lines treated with kinase inhibitors. The scripts and data are freely available at and via the ProteomeXchange with identifier PXD015606.

This study investigated the direct roles of hydrogen peroxide (H 2 O 2 ) in kidney aging using transgenic mice overexpressing glutathione peroxidase-1 (GPX1 TG). We demonstrated that kidneys in old mice recapitulated kidneys in elderly humans and were characterized by glomerulosclerosis, tubular atrophy, interstitial fibrosis, and loss of cortical mass. Scavenging H 2 O 2 by GPX1 TG significantly reduced mitochondrial and total cellular reactive oxygen species (ROS) and mitigated oxidative damage, thus improving these pathologies. The potential mechanisms by which ROS are increased in the aged kidney include a decreased abundance of an anti-aging hormone, Klotho, in kidney tissue, and decreased expression of nuclear respiratory factor 2 (Nrf2), a master regulator of the stress response. Decreased Klotho or Nrf2 was not improved in the kidneys of old GPX1 TG mice, even though mitochondrial morphology was better preserved. Using laser capture microdissection followed by label-free shotgun proteomics analysis, we show that the glomerular proteome in old mice was characterized by decreased abundance of cytoskeletal proteins (critical for maintaining normal glomerular function) and heat shock proteins, leading to increased accumulation of apolipoprotein E and inflammatory molecules. Targeted proteomic analysis of kidney tubules from old mice showed decreased abundance of fatty acid oxidation enzymes and antioxidant proteins, as well as increased abundance of glycolytic enzymes and molecular chaperones. GPX1 TG partially attenuated the remodeling of glomerular and tubule proteomes in aged kidneys. In summary, mitochondria from GPX1 TG mice are protected and kidney aging is ameliorated via its antioxidant activities, independent and downstream of Nrf2 or Klotho signaling., (© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Our discovery of low-threshold stimulation-induced locomotion in the pedunculopontine nucleus (PPN) led to the clinical use of deep brain stimulation (DBS) for the treatment of disorders such as Parkinson's disease (PD) that manifest gait and postural disorders. Three additional major discoveries on the properties of PPN neurons have opened new areas of research for the treatment of motor and arousal disorders. The description of (a) electrical coupling, (b) intrinsic gamma oscillations, and (c) gene regulation in the PPN has identified a number of novel therapeutic targets and methods for the treatment of a number of neurological and psychiatric disorders. We first delve into the circuit, cellular, intracellular, and molecular organization of the PPN, and then consider the clinical results to date on PPN DBS. This comprehensive review will provide valuable information to explain the network effects of PPN DBS, point to new directions for treatment, and highlight a number of issues related to PPN DBS.

Alzheimer's disease (AD) is characterized by a compromised blood-brain barrier (BBB) and disrupted intracellular calcium homeostasis in the brain. Therefore, rectifying the BBB integrity and restoring calcium homeostasis could provide an effective strategy to treat AD. Recently, we developed a high throughput-screening assay to screen for compounds that enhance a cell-based BBB model integrity, which identified multiple hits among which is granisetron, a Food and Drug Administration approved drug. Here, we evaluated the therapeutic potential of granisetron against AD. Granisetron was tested in C57Bl/6J young and aged wild-type mice, and in a transgenic mouse model of AD namely TgSwDI for its effect on BBB intactness and amyloid-β (Aβ)-related pathology. Our study findings showed that granisetron enhanced BBB integrity in both aged and TgSwDI mice. This effect was associated with an overall reduction in Aβ load and neuroinflammation in TgSwDI mice brains. In addition, and supported by proteomics analysis, granisetron significantly reduced Aβ induced calcium influx in vitro, and rectified calcium dyshomeostasis in TgSwDI mice brains by restoring calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, which was associated with cognitive improvement. These results support granisetron repurposing as a potential drug to hold, slow, and/or treat AD.

Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked two cigarettes 1 h apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles., Methods: This is a cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine, MG, and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman correlation, χ 2 , and ANCOVA adjusted for gender, race, and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised partial least squares-discriminant analysis (PLS-DA) was carried out for the classification of metabolomics profiles., Results: MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol versus nonmenthol smokers. Among menthol smokers, 42 metabolites were significantly correlated with MG boost, which linked to cellular functions, such as of cell death, survival, and movement., Conclusions: Plasma MG boost is a new smoking behavior biomarker that may provide novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes., Impact: These results provide insight into the biological effect of menthol smoking. Cancer Epidemiol Biomarkers Prev; 26(1); 51-60. ©2016 AACR., (©2016 American Association for Cancer Research.)

Previous studies have shown that protease-activated receptors (PARs) play an important role in various physiological processes. In the present investigation, we determined the expression of PARs on human lung fibroblasts (HLF-1) and whether they were involved in cellular differentiation and pro-inflammatory cytokine and prostaglandin (PGE2) secretion. PAR-1, PAR-2, PAR-3, and PAR-4 were detected in fibroblasts using RT-PCR, immunocytochemistry, and flow cytometry. Increased expression of PAR-4, but not other PARs, was observed in fibroblasts stimulated with phorbol myristate acetate. The archetypical activators of PARs, namely, thrombin and trypsin, as well as PAR-1 and PAR-2 agonist peptides, stimulated transient increases in intracellular Ca(2+), and promoted increased α-smooth muscle actin expression. The proteolytic and peptidic PAR activators also stimulated the release of IL-6 and IL-8, as well as PGE2, with a rank order of potency of PAR-1 > PAR-2. The combined stimulation of PAR-1 and PAR-2 resulted in an additive release of both IL-6 and IL-8. In contrast, PAR-3 and PAR-4 agonist peptides, as well as all the PAR control peptides examined, were inactive. These results suggest an important role for PARs associated with fibroblasts in the modulation of inflammation and remodeling in the airway., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Protease-activated receptors (PARs) are widely distributed in human airways, and recent evidence indicates a role for PARs in the pathophysiology of inflammatory airway disease. To further investigate the role of PARs in airway disease, we determined the expression and function of PARs in a murine model of respiratory tract viral infection. PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein were expressed in murine airways, and confocal microscopy revealed colocalization of PAR-2 and cyclooxygenase (COX)-2 immunostaining in basal tracheal epithelial cells. Elevated levels of PAR immunostaining, which was particularly striking for PAR-1 and PAR-2, were observed in the airways of influenza A/PR-8/34 virus-infected mice compared with sham-infected mice. Furthermore, increased PAR-1 and PAR-2 expression was associated with significant changes in in vivo lung function responses. PAR-1 agonist peptide potentiated methacholine-induced increases in airway resistance in anesthetized sham-infected mice (and in indomethacin-treated, virus-infected mice), but no such potentiation was observed in virus-infected mice. PAR-2 agonist peptide transiently inhibited methacholine-induced bronchoconstriction in sham-infected mice, and this effect was prolonged in virus-infected mice. These findings suggest that during viral infection, the upregulation of PARs in the airways is coupled to increased activation of COX and enhanced generation of bronchodilatory prostanoids.

1. Inhaled diethylenetriamine nitric oxide adduct (DETA/NO) has been shown to be a selective pulmonary vasodilator in animal and human studies. The aims of the present study were to investigate the effect of DETA/NO on mouse precontracted isolated tracheal smooth muscle preparations and to determine the active component of this compound. 2. Mouse isolated tracheal smooth muscle rings were precontracted with carbachol (10-7 mol/L). Changes in isometric tension were recorded after cumulative addition of DETA (30-300 micromol/L; n = 6), DETA/NO (30-300 micromol/L; n = 9) or diluent control (n = 3). In addition, some preparations (n = 5) were pretreated with the soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 30 micromol/L) before precontraction and exposure to DETA/NO. 3. Addition of DETA/NO caused a concentration-dependent relaxation of tracheal smooth muscle at 100 and 300 micromol/L, with an EC25%R of 109 micromol/L (95% confidence interval 72.6-164 micromol/L). The nucleophile amine carrier DETA had no effect on isometric tension. However, the relaxant effect of DETA/NO was completely abolished by pretreatment with ODQ. 4. We conclude that DETA/NO induces a concentration-dependent relaxation of mouse carbachol-contracted isolated tracheal smooth muscle that is mediated by NO released from DETA/NO via the activation of sGC.

Protease-activated receptors (PARs) are G-protein-coupled, seven transmembrane domain receptors that act as cellular enzyme sensors. These receptors are activated by the proteolytic cleavage at the amino terminus, enabling interaction between the newly formed "tethered ligand" and the second extracellular loop of the receptor to confer cellular signalling. PARs can also be activated by small peptides that mimic the tethered ligand. In the respiratory tract, PARs may be regulated by endogenous proteases, such as airway trypsin and mast cell tryptase, as well as exogenous proteases, including inhaled aeroallergens such as those from house dust mite faecal pellets. Immunoreactive PARs have been identified in multiple cell types of the respiratory tract, and PAR activation has been reported to stimulate cellular mitogenesis and to promote tissue inflammation. Activation of PARs concurrently stimulates the release of bronchorelaxant and anti-inflammatory mediators, which may serve to induce cytoprotection and to minimise tissue trauma associated with severe chronic airways inflammation. Furthermore, airway inflammatory responses are associated with increased epithelial PAR expression and elevated concentrations of PAR-activating, and PAR-inactivating, proteases in the extracellular space. On this basis, PARs are likely to play a regulatory role in airway homeostasis, and may participate in respiratory inflammatory disorders, such as asthma and chronic obstructive pulmonary disease. Further studies focussing on the effects of newly developed PAR agonists and antagonists in appropriate models of airway inflammation will permit better insight into the role of PARs in respiratory pathophysiology and their potential as therapeutic targets.

1. The potential mediator role of the prostanoid PGE(2) in airway smooth muscle relaxations induced by peptidic and proteolytic activators of PAR-1, PAR-2, PAR-3 and PAR-4 was investigated in carbachol-precontracted mouse isolated tracheal segments. 2. The tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced smooth muscle relaxation that was abolished by the non-selective cyclo-oxygenase (COX) inhibitor, indomethacin. The relative order for mean peak relaxation was SLIGRL-NH(2)>GYPGKF-NH(2) approximately amp; SFFLRN-NH(2)>SFNGGP-NH(2). 3. SFFLRN-NH(2), SLIGRL-NH(2) and GYPGKF-NH(2), but not SFNGGP-NH(2), induced significant PGE(2) release that was abolished by indomethacin. Like that for relaxation, the relative order for mean PGE(2) release was SLIGRL-NH(2)>GYPGKF-NH(2)>SFFLRN-NH(2)>SFNGGP-NH(2). 4. In dose-response studies, SLIGRL-NH(2) induced concentration-dependent increases in PGE(2) release (EC(50)=20.4 microM) and smooth muscle relaxation (EC(50)=15.8 microM). 5. The selective COX-2 inhibitor, nimesulide, but not the COX-1 inhibitor valeryl salicylate, significantly attenuated SLIGRL-NH(2)-induced smooth muscle relaxation and PGE(2) release. 6. Exogenously applied PGE(2) induced potent smooth muscle relaxation (EC(50)=60.3 nM) that was inhibited by the mixed DP/EP(1)/EP(2) prostanoid receptor antagonist, AH6809. SLIGRL-NH(2)-induced relaxation was also significantly inhibited by AH6809. 7. In summary, the results of this study strongly suggest that PAR-mediated relaxation in murine tracheal smooth muscle is dependent on the generation of the spasmolytic prostanoid, PGE(2). PAR-stimulated PGE(2) release appears to be generated preferentially by COX-2 rather than COX-1, and induces relaxation via activation of the EP(2) receptor.

Relaxant and contractile effects of the tethered ligand domain sequences of murine PAR-1, PAR-2, PAR-3 and PAR-4, and of the proteases thrombin and trypsin were examined in mouse isolated tracheal preparations. The epithelium- and cyclo-oxygenase-dependence of these effects and the potential modulatory effects of respiratory tract viral infection were also investigated. In carbachol-contracted preparations, trypsin, thrombin, and the tethered ligand domain sequences of murine PAR-1 (SFFLRN-NH(2)), PAR-2 (SLIGRL-NH(2)) and PAR-4 (GYPGKF-NH(2)), but not PAR-3 (SFNGGP-NH(2)), induced transient, relaxant responses that were abolished by the cyclo-oxygenase inhibitor indomethacin. Repeated administration of SFFLRN-NH(2), SLIGRL-NH(2) or GYPGKF-NH(2) (30 microM) was associated with markedly diminished relaxation responses (homologous desensitization), although there was no evidence of cross-desensitization between these peptides. The tethered ligand domain sequences for PAR-1 and PAR-4 induced a rapid, transient contractile response that preceded the relaxant response. Contractions were not inhibited by indomethacin and were not induced by either thrombin or trypsin. Influenza A virus infection did not significantly affect the responses induced by either the proteases or peptides. Furthermore, epithelial disruption caused by mechanical rubbing had no significant effect on responses to these PAR activators in preparations from either virus- or sham-infected mice. In summary, the proteases trypsin and thrombin, and peptide activators of PAR-1, PAR-2 and PAR-4 induced relaxant responses of mouse isolated tracheal smooth muscle preparations, which were mediated by a prostanoid, probably PGE(2). Interestingly, PAR-mediated relaxations were not significantly diminished following acute damage to the epithelium caused by mechanical rubbing and/or the respiratory tract viral pathogen, influenza A. British Journal of Pharmacology (2000) 129, 63 - 70.

This study was undertaken to observe whether dialysis-induced alveolar hypoventilation and arterial hypoxaemia occur during bicarbonate haemodialysis in patients receiving partial mechanical support with pressure support ventilation. Nineteen patients admitted to the medical intensive care unit requiring mechanical ventilation and haemodialysis were enrolled. Arterial blood gas, white blood cell (WBC) count, minute ventilation, respiratory rate, breathing pattern and blood pressure were measured according to the following time schedule: pre-dialysis (time 0), and at 15, 30, 60, 120, 180, 240 min thereafter. Results showed that, with the use of cuprammonium dialyser, the WBC count dropped immediately and reached the nadir 15 min after haemodialysis. Thereafter, it recovered and overshot the pre-dialysis values until the end of dialysis. The bicarbonate dialysate indeed resulted in rapid and significant metabolic alkalosis. However, no decrease of PaO2 occurred throughout haemodialysis. The tidal volume, minute ventilation and breathing pattern remained stable during haemodialysis. We conclude that neither dialysis-induced alveolar hypoventilation nor arterial hypoxaemia developed during bicarbonate dialysis in patients mechanically ventilated with the pressure support ventilation.

Purpose: To determine the diagnostic value of pleural fluid telomerase activity in distinguishing a malignant from a nonmalignant pleurol effusion in a cohort of patients undergoing thoracentesis., Patients and Methods: Using a polymerase chain reaction (PCR)-based assay, telomerase activity was examined in the pleural fluid cells obtained from 144 consecutive, unselected patients. According to the final diagnosis achieved, these patients were classified into three groups: group I consisted of 70 malignant pleural effusions diagnosed by either fluid cytology or pleural biopsy, group II consisted of 52 nonmalignant pleural effusions, and another 22 samples were categorized to be suspicious malignant pleural effusions (group III) due to inconclusive results in effusion cytology and percutaneous pleural biopsy, but were strongly suspicious in clinical settings., Results: The presence of telomerase activity was observed in 64 of 70 samples in group I (91.4%), three of 52 samples in group II (5.8%), and 20 of 22 samples in group III. All three nonmalignant, telomerase-positive pleural effusion samples in group II were obtained from patients with tuberculosis. As a diagnostic criterion for malignant pleural effusion in group I and group II patients, positive telomerase activity had a sensitivity of 91.4%, a specificity of 94.2%, and a positive and negative predictive value of 0.96 and 0.89, respectively., Conclusion: Our results indicate that the detection of telomerase activity may be a useful adjunct to cytopathologic methods in the diagnosis of malignant pleural effusions.

The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.

Background: In patients who have malignant pleural effusion, it is difficult to diagnose trapped lung before thoracoscopy, thoracostomy, and drainage of the effusion. Predicting the outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung is also difficult., Objective: To investigate the factors that may be useful in diagnosing trapped lung and predicting the outcome of pleurodesis., Design: Prospective cohort study., Setting: University medical center., Patients: 65 patients with symptomatic malignant pleural effusion., Intervention: A chest tube was inserted for drainage of the effusion, and pleurodesis was done using bleomycin as the sclerosant., Measurements: The pH and glucose levels of the effusion and the elastance of the pleural space (defined as the decline in pleural fluid pressure in cm H2O after removal of 500 mL of effusion) were measured. The outcome of pleurodesis was evaluated 1 month after the chest tube was removed., Results: Patients with an elastance of 19 cm H2O or more had a higher incidence of trapped lung (11 of 14 patients) than did those with an elastance less than 19 cm H2O (3 of 51 patients) (P < 0.001). None of the 14 patients with an elastance of 19 cm H2O or more and none of the 14 patients with a trapped lung had successful pleurodesis. Forty-two of 43 patients with an elastance less than 19 cm H2O who did not have a trapped lung had successful pleurodesis. Elastance seemed to be the best predictor for trapped lung and outcome of pleurodesis, although outcome was also correlated with pH and glucose levels of the effusion. Low-dose bleomycin (30 mg) is as effective as the usual dose of bleomycin (60 mg) for pleurodesis., Conclusion: In patients with symptomatic malignant pleural effusion, measurement of the elastance of the pleural space is a simple and effective method for the diagnosis of trapped lung and prediction of the outcome of chemical pleurodesis with bleomycin.

An 18-month-old girl was brought to the emergency room of Chang Gung Children's Hospital with inspiratory stridor, suprasternal retractions and imminent respiratory failure. Despite orotracheal intubation, persistent poor air-entry was noted. Flexible bronchoscopy via the endotracheal tube showed a copious amount of mucopurulent secretions in the tracheobronchial tree without any foreign bodies. With vigorous suctioning and antibiotic treatment, she had a rapid recovery. Tracheal aspirates showed a growth of Haemophilus influenzae. Cefamandole was used with good response. In conclusion, although bacterial tracheitis is an uncommon obstructive upper airway disease in children, using a bronchoscope to diagnose and to guide specific therapy can decrease the morbidity and mortality.

A heterogeneous group of 11 children with atelectasis persisting longer than one month were investigated for the causes using chest computed tomography and fiberoptic bronchoscope. Four young infants had right upper lobe (RUL) posterior segmental atelectasis simulating RUL lobar collapse in plain chest films; all had only two visible segmental bronchi by bronchoscopic examination. Intraluminal obstruction in the central airway was not a common cause of pediatric chronic atelectasis in this small series of patients. Only one obstructive atelectasis caused by dilated pulmonary arteries was detected in this study. Two patients with pre-existing neuromuscular diseases showed multiple atelectasis. The atelectatic lobes do not spontaneously re-inflate following flexible bronchoscopy. Investigations involving a larger number of cases are needed to substantiate the etiologies and to guide specific therapy for those children with chronic atelectasis.

To evaluate the characteristics of and acceptance by persons in Taiwan who currently use positive-pressure mechanical ventilation at home (HMV), a survey was conducted in August 1992 through home care and equipment providers to investigate these patients. The 34 cases enrolled, including 18 males and 16 females, were classified into four groups: (1) lung disease group (LD) (n = 7) including chronic obstructive pulmonary disease and bronchiectasis; (2) neuromuscular group (NM) (n = 14) including diverse neuromuscular diseases; (3) spinal disease group (SP) (n = 7) including spinal cord injuries or tumors and (4) unresponsive stroke group (US) (n = 6). The average age of the SP group was much younger than those of the other three groups. The duration of home ventilation was from 1 to 36 months, with a mean duration of 10.6 +/- 8.7 months. Fifteen cases had received HMV for more than one year. Twenty six (76.5%) of the patients were completely dependent. All of the US patients had to be ventilated all day long in contrast to 71.4% of LD completely dependent. The cost of the US group was higher than that of the other three groups. Two of the LD, five of NM and one US patient had been re-admitted because of pneumonia, tracheostomy wound infection, granulation formation or weaning problems before the study. A follow-up survey was done four months, then one year later. The survival rate was 16.7% for LD group, 50% for NM and US group. Of the SP group, all patients were surviving at the end of this study. Most of the present HMV users were satisfied with their setting. It was concluded that HMV is an acceptable alternative way of therapy for long-term ventilation patients in Taiwan. SP and NM patients are better candidates for HMV. The overall one year survival rate is promising, while SP patients had the best prognosis. Patients who had already used HMV for more than 11 months, regardless of the disease, have a better chance to live another year.

We experienced six cases of congenital tracheal stenosis during a 3 years' period from October 1991 to September 1994 in Chang Gung Children's Hospital, Taiwan. The presenting symptoms of congenital tracheal stenosis varied from acute obstructive upper respiratory episodes in young childhood, stridor and wheezing since birth, recurrent bronchiolitis, difficult to intubate with endotracheal tube. Although bronchoscopy was diagnostic, but further imaging studies without anesthesia were equivocal. In spite of pericardial patch-tracheoplasties, the two cases undergoing surgery expired. During follow-ups, the remaining four patients suffered from persisting noisy respiration by conservative management.

One hundred and forty-one flexible fiberoptic bronchoscopies were performed in 124 pediatric patients in Chang Gung Children's Hospital between October 1991 and September 1994. Eleven of these patients were younger than 1 month old; 52 patients were younger than 1 year old; 94 patients were younger than 6 years old. The bronchoscope used was Olympus BF 3C20; with a 3.5 mm outer diameter, it also has a build-in 1.2 mm working channel. Most of the procedures were done in the pediatric intensive care unit. Oral chloral hydrate and parenteral benadryl were given as pre-sedation medication 30 minutes before the procedures; for most cases intravenous midazolam and meperidine hydrochloride were given immediately before the examination. The most common diagnoses were laryngomalacia, airway foreign bodies, subglottic stenosis or tracheal stenosis. Six episodes of transient hypoxemia and one brief episode of apnea were encountered. It was concluded that flexible fiberoptic bronchoscopy, very useful and safe in pediatric patients, has been underused in Taiwan.

Pulmonary echinococcosis is a rare disease in Taiwan and has never been reported in Taiwan's literatures. Here we report an overseas Chinese from Calcutta, India, presenting with recurrent hemoptysis and chest pain and with two big lung masses on chest roentgenogram. Rupture and spike fever ensured after fine needle aspiration of the cysts. Successful surgical intervention was obtained and echinococcal infection was documented pathologically.

Background: Accurate diagnosis of peripheral pulmonary lesions usually relies on fluoroscopic guided procedures. As fluoroscopy is not routinely available in many respiratory units, an approach not using fluoroscopy but with a high diagnostic yield is highly desirable., Methods: Immediate cytological examination of multiple brushings using Riu's stain, a modified Wright's stain, was performed in 38 patients with peripheral pulmonary lesions not visible at bronchoscopy. The results were compared with the final diagnoses determined by histological examination or subsequent Papanicolaou staining of cytological specimens and clinical course., Results: Of the 38 patients 29 were subsequently confirmed to have a malignant tumour. Our method provided a diagnosis of malignancy in 86% of these lesions. The accuracy (91%) and sensitivity (88%) were higher for lesions > 3 cm in diameter than for those of diameter < or = 3 cm (87% and 83%). There were no false positive results. The 29 lesions correctly diagnosed as malignant by Riu's stain required significantly fewer brushings (mean (SD) 3 (2)) than the nine benign lesions (5 (4))., Conclusions: This technique provides a high diagnostic yield, avoids the need for fluoroscopy, and is probably safer than percutaneous biopsy.

The introduction of flexible fiberoptic bronchoscopy into clinical use in 1968 had led a veritable explosion in the application of pulmonary endoscopy. In 1978, Wood and his colleagues, using a 3.5 mm Olympus 3C4 pediatric bronchoscope, expanded this technique to pediatric field. Up-to-now, they have more than 2000 bronchoscopies in pediatric patients, however, there has been no report in this field in Taiwan. I, using a new Olympus pediatric flexible fiberoptic bronchoscope 3C20, sedation and topic anesthesia, performed 24 airway examinations in 22 patients in the past 7-month period. The youngest patient was a 1672 gm, 4 day-old baby. The most frequent indication was stridor and most common diagnosis was laryngomalacia. The complications were not common and could have been avoidable if performed by an expert. My conclusion is that pediatric fiberoptic bronchoscopy is possible even in small babies less than 3 kg of weight.

Fifty-two patients with acute asthma requiring immediate therapy but not hospitalization were studied in an emergency department following conventional therapy with bronchodilators. After discharge, the patients were treated with a controlled regimen of long-acting theophylline and beta-agonist inhalation as necessary. They were randomly assigned to one of three groups using a double blind model. Group A received intramuscular and oral placebos. Group B received intramuscular dexamethasone injection along with oral placebo treatment. Group C received oral dexamethasone by a tapering schedule associated with placebo intramuscular injection. Follow-up was carried out 7 days after the treatment in the emergency room. There were no significant statistical differences in the relapse rate among the three groups. Those patients who received oral or intramuscular dexamethasone had a decrease in the need for beta-agonist inhalation and fewer respiratory symptoms. However, there was no significant statistical difference between groups B and C. It was concluded that repository steroids could reduce the respiratory symptoms and frequency of beta-agonist usage as effectively as oral steroid treatment. However, the steroids do not improve the relapse rate in patients with only mild symptoms.

We report a Chinese patient with hemoglobin H (Hb H) disease who developed intrathoracic extramedullary hematopoiesis (EMH) 17 years following splenectomy for a blunt abdominal injury. The patient initially presented with extreme hyperbilirubinemia and multiple intrathoracic tumors. Hb H disease was diagnosed after investigation, and the marked jaundice, which declined gradually after supportive treatment, was attributed to his chronic hemolysis superimposed on an acute hepatitis C virus infection. A biopsy of the intrathoracic tumors revealed an EMH. Intrathoracic EMH, which is usually encountered in patients with beta-thalassemia and hereditary spherocytosis, has never been reported in Hb H disease. In areas where thalassemia is prevalent, EMH should be considered in the differential diagnosis of patients who have chronic anemia with asymptomatic intrathoracic tumor to avoid unnecessary surgical interventions.

The mortality rate of WLTB was significantly higher than non-WLTB in 45 of 516 cases of PTB in a 24-month period. There is no known underlying disease predisposing to WLTB. Clinically, the patients were significantly more toxic and had lower serum albumin and hemoglobin levels than non-WLTB patients. They had a lower rate of positive PPD tuberculin skin tests. The chest roentgenograms revealed three patterns: (1) DBS type in 15--all with multiple or diffuse opacities with or without cavitations; (2) DHS type in 20--eight with typical miliary lesions and 12 with atypical miliary patterns; (3) combined focal PTB and DHS type in ten. We found that atypical chest roentgenographic patterns were common in WLTB and frequently led to misdiagnosis. The delayed diagnosis and treatment of this advanced disease resulted in the high mortality. Early, empirical antituberculosis chemotherapy is indicated and life-saving.

A broncholith is a calcified lymph node which partially or completely erodes into the bronchial lumen. Its manifestations are non-specific and may result in life-threatening complications. In Taiwan, pulmonary tuberculosis, one of the most common etiologies of broncholithiasis, is common. To our knowledge, no report on broncholithiasis can be found in literature in this country. We herein present three cases of broncholithiasis experienced in the past 11 years in Chang Gung Memorial Hospital. The presenting manifestations are obstructive pneumonia in two cases, and hemoptysis in the other one. In two of them, the broncholiths were located in the right side. Fiberoptic bronchoscopy was performed, and the stones were visible in all of them. Bronchoscopic removal of stone was successful in two cases, and the other coughed up stones spontaneously after bronchoscopies. In the absence of significant symptoms or complications, only observation is necessary. For the symptomatic borncholiths, we advocate that bronchoscopic removal is worth trying to eliminate the necessity of thoracotomy unless complications are present, which indicate surgical intervention such as massive hemoptysis, fistula formation between tracheobronchial trees and esophagus or vessels, recurrent pulmonary infection or suspicion of malignancy.

This study includes 140 episodes (138 cases) of Staphylococcus aureus septicemia, made up mostly of community-acquired, nonintravenous drug abuse (nonIVDA) cases. Unlike other series, injury wounds and skin or soft tissue infections were the most common sites of primary infection. In spite of a different patient population and lack of cases with tricuspid valvular endocarditis, the lungs were still the most common site of secondary infectious foci and most developed within two weeks of onset of the septicemia.

Nine cases of thoracic actinomycosis treated in the period from 1976 to 1990 were reviewed. Among them, 4 cases were children. The clinical symptoms and laboratory examinations were non-specific. Chest roentgenographic manifestations including nodular (3 cases), infiltrations (4 cases), and infiltrations with pleural changes (2 cases) were also non-specific. Chest wall masses were noted in four patients. There were no cases correctly diagnosed on admission. The diagnosis of thoracic actinomycosis was made from thoracotomy in 6 cases, from culture of chest wall mass incisional specimens in 2 cases and from bronchoscopic biopsy in 1. All the patients received antibiotics, however the varied duration of postoperative antibiotics did not change the outcome. No mortality or recurrence was noted in our 9 patients with a mean follow-up of 1.9 years (from 2 months to 6 years.) We conclude that surgical intervention is still the cardinal method for diagnosis and treatment. Establishment of the role of postoperative antibiotics will need further prospective study. The prognosis of thoracic actinomycosis is fairly good.

Mycoplasma pneumoniae (M. Pneumoniae) is a primarily pathogen of the respiratory tract. The clinical characteristics, laboratory findings, and roentgenographic patterns of 45 patients with serologically proven M. pneumoniae pneumonia admitted to Chang Gung Hospital from 1981 to 1989 have been reviewed. There were 23 males and 22 females. Forty-one (91%) were below 40 years old and 13 patients (29%) were below 5 years old. Fever, cough and chest rales were the most common symptoms and signs. A transient mild elevation of liver enzymes was seen in 33% of the patients, most of whom were below the age of ten (73%). A leukocyte count over 15,000/cu mm was not rare (16%). Roentgenographic features included unilateral infiltration (84%), lower lobe predominance (60%), and either confluent (56%) or patchy (33%) consolidation. Pleural effusion occurred in 24% of the patients. Complete resolution of chest roentgenography took from 8 to 42 days with a mean of 20 days. The response of fever to treatment with erythromycin took from 1 to 6 days with a mean of 3 days. There were no life threatening pulmonic or extrapulmonic complications.

The records of 121 patients admitted to the Medical Intensive Care Unit (MICU) of Chang Gung Memorial Hospital with severe chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation were reviewed retrospectively. Eighty-seven percent (20/23) of the patients with multifocal atrial tachycardia (MAT) expired during their ICU admission in contrast to 23.5% (23/98) of those without MAT. The only differences between these two groups were incidence of cor pulmonale, and right axis deviation, right bundle branch block, pulmonale P in electrocardiogram. MAT might be considered as a grave prognostic sign in patients with COPD severe enough to require mechanical ventilation.

A 47-year-old woman was admitted for bilateral lower lobe pneumonia with respiratory distress. Two episodes of respiratory failure developed despite improvement of pneumonia after antibiotic chemotherapy. Loss of consciousness and quadriplegia accompanied the last episode of respiratory failure. Arnold-Chiari malformation type 1 was diagnosed and a suboccipital craniectomy was performed. The neuromuscular and respiratory disorders greatly improved after operation. We believe that ACM 1 should be considered when an adult develops unexpected respiratory failure after improvement of the primary pulmonary condition. This disease is potentially treatable by surgical management, and if it is misdiagnosed, will be fatal.

Respiratory failure (RF) developed in 43 (40.2 percent) of 107 patients with acute organophosphate or carbamate poisoning; 22 (51.2 percent) died. The 64 patients who did not develop RF survived. All cases of RF developed within 96 hours after poisoning: within 24 hours in 35 patients (acute onset) and between 24 and 96 hours in eight patients (subacute onset). Severity of poisoning was the primary determinating factor for RF. Cardiovascular collapse and pneumonia were also associated with RF. In 19 patients with cardiovascular collapse, 17 had acute onset of RF and two had subacute onset. In 28 patients with pneumonia, 17 developed acute onset of RF and eight developed subacute onset. No organophosphorus compound caused RF more frequently than another. The duration of ventilator support for subacute RF was significantly longer than for acute RF (287 +/- 186 vs 115 +/- 103 hours, p = 0.02). The use of pralidoxime did not reduce the incidence of RF. We found that severity of poisoning, cardiovascular collapse, and pneumonia were the predisposing factors to RF. The golden time for treatment of acute organophosphate or carbamate poisoning was the initial 96 hours. No RF occurred after this time. Aggressive treatment and prevention of the above three factors will reduce the incidence of RF, or in other words, reduce the mortality.

A new, simpler method to re-expand collapsed lungs was introduced in 14 procedures in 12 critically ill patients. To close the bronchus, we wedge the fiberoptic bronchoscope into each segment or subsegment of the collapsed lung instead of using a balloon cuff. Room air was then insufflated into the atelectatic alveoli after repetitive sputum suctioning and bronchial washing with normal saline solution. Complete re-expansion was achieved in 12 of the 14 procedures and partial in two. The average alveolar-arterial oxygen pressure difference (P[A-a]O2) declined from 217.5 before the procedure to 200.3, 150.0 and 152.2, respectively at 30 minutes, 12 hours and 24 hours after. There were no complications.

The flexible fiberoptic bronchoscope was used to treat bronchial foreign bodies in 33 adults. The length of time that the foreign body was in the lung was less than 1 wk in six (acute group), more than 1 month in 21 (chronic group), and uncertain in two (uncertain group), and the foreign body was an endogenous broncholith in four patients (broncholith group). The foreign bodies were nonfragile, solid matter in most cases and they frequently had sharp projections on them. Granulations around the foreign body were common in the chronic group, but there was no correlation between the length of time the foreign body was in the lung and the amount of granulation or the number of the bronchoscopies needed for diagnosis or management. The granulations did not bleed easily on biopsy or during removal of the foreign body. In fact, they receded if several pieces were removed, making the foreign body much easier to recognize and to retrieve in the next bronchoscopy (about 1 wk later). After removal of the foreign body, the residual granulations regressed, and the bronchial lumen became more patent. The mortality, morbidity, and complication rates were very low, whereas the success rate was high. We conclude that flexible fiberoptic bronchoscopy is practical and safe in retrieving bronchial foreign bodies in adult patients.

Pancreatic pleural effusion due to an internal fistula is an uncommon and often unrecognized clinical syndrome which complicates chronic pancreatitis. It frequently presents with chest and respiratory symptoms of pleural effusion with little abdominal complaints, and history of previous pancreatic disease is often absent, making the diagnosis easily missed. A case of pancreatic pleural effusion due to an internal fistula is presented. To the best of our knowledge, this is the only case report in English journals on a pancreatico-pleural fistula resulting in pleural effusion that was not massive and the effusion amylase level was below 1,000 IU/L while being diagnosed. The potential of computed tomography in the diagnosis of this disease is illustrated.