Alveolar Level Research Articles

Transpalatal Distraction Using Bone-Borne Distractor: Clinical Observations and Dental and Skeletal Changes

The aim of this clinical study was to analyze the outcome, complications, and long-term results of transpalatal distraction for the correction of maxillary transverse deficiency (MTD) and assess skeletal and dental changes in the sagittal, vertical, and transverse planes through cephalograms and dental casts. Ten adult patients with MTD were treated with a Transpalatal Distractor (Surgi-Tec, Bruges, Belgium). Lateral and posteroanterior cephalometric films and dental casts were taken before surgery and at the end of the consolidation period. The statistical analysis of cephalometric film and dental cast measurements was undertaken with paired t tests. The intraoperative and postoperative problems encountered were damage to the central incisive teeth as a result of vertical osteotomy, wound dehiscence after the latent period, pain during the distraction period, and loosening of the distractor and buccal displacement of the left alveolar segment during the consolidation period. Model analysis showed that the greatest amount of transverse increase was in the premolar region (7.07 mm for first premolar and 7.10 mm for second premolar). Frontal cephalometric analysis indicated that transverse distances increased more at the alveolar level (7.75 mm) than in the maxillary base (5.25 mm) and nasal region (4.3 mm). The asymmetries between the left and right sides in both dental and skeletal expansions were statistically nonsignificant. The changes in the Sella-nasion-point A, Sella-nasion-point B, Sella-nasion and gonion-gnasion angles were statistically significant. According to the results of this study, transpalatal distraction was found to be a clinically effective technique for palatal expansion in adult patients with MTD. However, treatment planning and regular clinical follow-up visits are necessary for long-term clinical success.

Pulmonary Cytokine Responses During Mechanical Ventilation of Noninjured Lungs With and Without End-Expiratory Pressure

Positive end-expiratory pressure (PEEP) during mechanical ventilation may impose different degrees of stress on healthy lungs. On the assumption that stress is reflected by cytokine production, we performed a translational study investigating the effect of PEEP on bronchoalveolar and systemic mediator levels in isolated perfused mouse lungs (IPL) and in patients with healthy lungs. (Part I) IPL were ventilated with end-expiratory pressures of 0, 3, 6, or 10 cm H2O and end-inspiratory pressure (EIP) levels of 10 or 25 cm H2O. Interleukin (IL)-6 and macrophage inflammatory protein-2 concentrations in the venous effluate were monitored. (Part II) Patients (nonsmokers) scheduled for elective otorhinolaryngology surgery (duration>90 min) were randomized to receive either ventilation with zero end-expiratory pressure or PEEP (10 cm H2O). Mediators in bronchoalveolar lavage, nuclear factor kappaB, (NF-kappaB)-activation in alveolar macrophages and circulating systemic mediators were monitored. Control patients underwent bronchoalveolar lavage after intubation. In the IPL, mediator concentrations increased with increasing end-expiratory pressure at an EIP of 10 cm H2O, but decreased at 25 cm H2O EIP. In patients, bronchoalveolar IL-6, monocyte chemoattractant protein-1, and granulocyte monocyte-colony stimulating factor were increased by ventilation regardless of the PEEP level. IL-6 and IL-8 levels were moderately increased by PEEP but not zero end-expiratory pressure. Nuclear factor kappaB DNA binding activity in alveolar macrophages and systemic mediator levels did not change. On the basis of the premise that cytokine levels may indicate mechanical stress, our findings indicate that even low tidal volume ventilation causes some stress. PEEP is beneficial at high inspiratory pressure, but imposes moderate stress at low inspiratory pressure.

Understanding anesthesia through functional imaging

This review will highlight the recent functional magnetic resonance imaging, positron emission tomogram scan and connectivity studies in anesthesia and analgesia. In regional cerebral blood flow (rCBF) studies with isoflurane and sevoflurane, there is a consistent pattern of rise in rCBF in the anterior cingulate cortex and insula while the thalamus, lingual cortex and cerebellum show a decrease in rCBF, in a dose range of 0.2-1 minimum alveolar concentration. Even 0.25 minimum alveolar concentration causes a predominant decrease of rCBF in the cortical regions and increase of rCBF in the subcortical regions. This minimum alveolar concentration level primarily affects the association cortices. Thalamus and thalamo-cortical pathways seem to be linked to the hypnotic effects of anesthesia and deep sedation. Connectivity studies also confirm this. The electroencephalogram equivalent of this appears to be a transition from 'alpha' wave activity to 'delta' wave activity. Anterior cingulate cortex, S1 and S2 are the regions consistently activated in acute pain. Remifentanil infusion in acute pain decreases the activation in pain perception regions while activating the pain modulation regions. In chronic pain states, prefrontal cortex and insula are activated whereas there is a decrease in activity in the thalamus. Slowly, a pattern of neuronal activity reflecting hypnosis, analgesia, amnesia and reflex suppression seems to be emerging giving us a better insight into the central nervous system effects of anesthesia.

Rebuttal from Drs. Hughes and West

POINT-COUNTERPOINTRebuttal from Drs. Hughes and WestPublished Online:01 May 2008https://doi.org/10.1152/japplphysiol.01092.2007bMoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat The areas of agreement in this debate are twofold: 1) mean pulmonary blood flow per horizontal slice [per unit volume or, more accurately, per unit density or “alveolus” (1,6)] increases in the gravity direction, independent (for the most part) of postural orientation, 2) there is considerable inhomogeneity of blood flow within a slice of minimal vertical height. Heterogeneity, whether random or ordered, is inevitable as the spatial resolution increases, just as the length of the shoreline increases indefinitely as the sample size gets smaller. Suffice to say that there are two extremes, 1) a well-expanded, vasodilated lung with low PVR and a mean Ppa level below the top of the lung, and 2) a low volume vasoconstricted lung with high PVR and a Ppa level greater than the lung's vertical height. The effects of gravity will be prominent in the former and largely obscured in the latter.The core of the debate is about the mechanisms responsible for pulmonary blood flow heterogeneity. There has been acceptance (for more than 40 yr) that mean pulmonary blood flow per horizontal slice is influenced by the relations between Ppa, Palv, and Pv (zones I, II, and III) (7), provided the lung is well expanded and PVR is normal. But what determines heterogeneity at the same horizontal level? Between acini, or larger domains, the Seattle group maintains that the architecture of the vascular tree (presumably, arterial) determines local vascular resistance and blood flow by, for example, uneven diameters of the two daughter vessels at a bifurcation. Glenny (5) maintains that this is not random, but forms part of the fractal design of the lung (4). Against this hypothesis is 1) the arterial system contributes only 40% to total PVR (2), and 2) the compliance of the arterial tree means diameters are not fixed, but respond to changes of smooth muscle tone or intra- or extravascular pressures (themselves influenced by gravity from distortion of the lung by its own weight and by other intrathoracic structures).Distal to the arterial tree, at the alveolar septal level, recruitment and distension of vessels occurs (3), independent of arteriolar domains (8), as input pressure increases and exceeds critical opening pressure (9); in the lung periphery, input pressures are a function of vertical height and gravity. So, in subtle ways, gravity may interact with compliant vascular structures to influence local PVR within as well as between horizontal lung slices.REFERENCES1 Anthonisen NR, Milic-Emili J. Distribution of pulmonary perfusion in erect man. J Appl Physiol 21: 760–766, 1966.Link | ISI | Google Scholar2 Dawson CA. Dynamics of blood flow and pressure-volume relationship. In: The Lung: Scientific Foundations, edited by Crystal RG, West JB, et al. Philadelphia: Lippincott-Raven, 1997, p. 1503–1522.Google Scholar3 Glazier JB, Hughes JMB, Maloney JE, West JB. Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J Appl Physiol 26: 65–76, 1969.Link | ISI | Google Scholar4 Glenny RW, Robertson HT. Fractal modelling of pulmonary blood flow inhomogeneity. J Appl Physiol 70: 1024–1030, 1991.Link | ISI | Google Scholar5 Glenny RW. Spatial correlation of regional pulmonary perfusion. J Appl Physiol 72: 2378–2386, 1992.Link | ISI | Google Scholar6 Hughes JMB, Glazier JB, Maloney JE, West JB. Effect of lung volume on the distribution of pulmonary blood flow in man. Respir Physiol 4: 58–72, 1968.Crossref | Google Scholar7 West JB, Dollery CT, Naimark A. Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures. J Appl Physiol 19: 713–724, 1964.Link | ISI | Google Scholar8 Warrell DA, Evans JW, Clarke RO, Kingaby JP, West JB. Pattern of filling in the pulmonary vascular bed. J Appl Physiol 32: 346–356, 1972.Link | ISI | Google Scholar9 West JB, Schneider AM, Mitchell MM. Recruitment in networks of pulmonary capillaries. J Appl Physiol 39: 976–984, 1975.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 104Issue 5May 2008Pages 1535-1535 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01092.2007bHistory Published online 1 May 2008 Published in print 1 May 2008 Metrics

Evaluation of antitubercular drug‐loaded surfactants as inhalable drug‐delivery systems for pulmonary tuberculosis

Pulmonary tuberculosis is associated with a year-long chemotherapy, poor alveolar drug levels, drug-related systemic toxicity, and patient noncompliance. In this study, exogenous pulmonary surfactant is proposed as a drug carrier for antitubercular drugs. Dipalmitoylphosphatidylcholine (DPPC), the major lung-surfactant lipid, has been combined with antitubercular drugs isoniazid (INH), rifampicin (RFM), and ethambutol (ETH) in 1:1 ratio by weight, in which drugs had a ratio of 1:2:3 by weight. At 37 degrees C, the formulation had better surfactant function with quicker reduction of surface tension on adsorption (32.71 +/- 0.65 mN/m) than DPPC liposomes (44.67 +/- 0.57 mN/m) and maintained 100% airway patency in a capillary surfactometer. Drug-loaded surfactant liposomes were about 2 microm and had entrapment efficiency of 30.04% +/- 2.05%, 18.85% +/- 2.92%, and 61.47% +/- 3.32% for INH, RFM, and ETH, respectively. Sustained release of the drugs from surfactants was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger showed 12.06% +/- 1.87% of INH, 43.30% +/- 0.87% of RFM, and 22.07% +/- 2.02% of ETH deposited in the alveolar chamber upon nebulization for a minute using a jet nebulizer. The formulation was biocompatible and stable with physicochemical properties being retained even after storage for a month at 4 degrees C. Antitubercular drug-loaded surfactants developed could serve dual purposes of alveolar stabilization due to surfactant action and better reach of these drugs to the alveoli due to antiatelectatic effect of the surfactant.

Triggering receptors expressed on myeloid cells in pulmonary aspiration syndromes

To investigate the potential role of serum and alveolar soluble triggering receptor expressed on myeloid cells (sTREM-1) as a biological marker of pulmonary aspiration syndromes. Prospective cohort study. University-affiliated intensive care unit. Seventy-five patients with pulmonary aspiration and 13 controls receiving mechanical ventilation. Blood and bronchoalveolar lavage (BAL) fluid samples were collected on enrollment. Soluble TREM-1 levels were measured by an enzyme-linked immunosorbent assay. Thirty-eight of 75 participants had documented BAL culture-positive pulmonary aspiration. While circulating levels of sTREM-1 were comparable between those with aspiration syndromes (19.81 +/- 12.09 pg/ml) and controls (15.96 +/- 11.16 pg/ml) (p=0.27), the alveolar levels of sTREM-1 were higher in patients with culture-positive pulmonary aspiration (344.41 +/- 152.82 pg/ml) compared with those culture-negative pulmonary aspiration (142.76 +/- 89.88 pg/ml; p < 0.001). A cut-off value of 250 pg/ml for alveolar sTREM-1 achieved a sensitivity of 65.8% (95% CI 48.6-80.4) and a specificity of 91.9% (95% CI 78.1-98.2) with an area under the curve of 0.87 (95% CI 0.78-0.94). Alveolar sTREM-1 levels can be a potential biomarker for distinguishing BAL culture-positive from BAL culture-negative pulmonary aspiration.

Cerebral spectroscopic and oxidative stress studies in patients with schizophrenia who have dangerously violently offended

BackgroundThe aim of this study was to bring together all the results of in vivo studies of ethane excretion and cerebral spectroscopy in patients with schizophrenia who have dangerously seriously violently offended in order to determine the extent to which they shed light on the degree to which the membrane phospholipid hypothesis and the actions of free radicals and other reactive species are associated with cerebral pathophysiological mechanisms in this group of patients.MethodsThe patients investigated were inpatients from a medium secure unit with a DSM-IV-TR diagnosis of schizophrenia. There was no history of alcohol dependency or any other comorbid psychoactive substance misuse disorder. Expert psychiatric opinion, accepted in court, was that all these patients had violently offended directly as a result of schizophrenia prior to admission. These offences consisted of homicide, attempted murder or wounding with intent to cause grievous bodily harm. Excreted ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). 31-phosphorus magnetic resonance spectroscopy data were obtained at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm3 voxel).ResultsCompared with age- and sex-matched controls, in the patient group the mean alveolar ethane level was higher (p < 0.0005), the mean cerebral beta-nucleotide triphosphate was lower (p < 0.04) and the mean gamma-nucleotide triphosphate was higher (p < 0.04). There was no significant difference between the two groups in respect of phosphomonoesters, phosphodiesters or broad resonances.ConclusionOur results are not necessarily inconsistent with the membrane phospholipid hypothesis, given that the patients studied suffered predominantly from positive symptoms of schizophrenia. The results suggest that there is increased cerebral mitochondrial oxidative phosphorylation in patients with schizophrenia who have dangerously and seriously violently offended, with an associated increase in oxygen flux and subsequent electron 'leakage' from the electron transport chain leading to the formation of superoxide radicals and other reactive oxygen species. In turn, these reactive species might cause increased lipid peroxidation in neuroglial membranes, thereby accounting for the observation of increased ethane excretion.

Cerebral spectroscopic and oxidative stress studies in patients with schizophrenia who have dangerously violently offended

The aim of this study was to bring together all the results of in vivo studies of ethane excretion and cerebral spectroscopy in patients with schizophrenia who have dangerously seriously violently offended in order to determine the extent to which they shed light on the degree to which the membrane phospholipid hypothesis and the actions of free radicals and other reactive species are associated with cerebral pathophysiological mechanisms in this group of patients. The patients investigated were inpatients from a medium secure unit with a DSM-IV-TR diagnosis of schizophrenia. There was no history of alcohol dependency or any other comorbid psychoactive substance misuse disorder. Expert psychiatric opinion, accepted in court, was that all these patients had violently offended directly as a result of schizophrenia prior to admission. These offences consisted of homicide, attempted murder or wounding with intent to cause grievous bodily harm. Excreted ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). 31-phosphorus magnetic resonance spectroscopy data were obtained at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm3 voxel). Compared with age- and sex-matched controls, in the patient group the mean alveolar ethane level was higher (p < 0.0005), the mean cerebral beta-nucleotide triphosphate was lower (p < 0.04) and the mean gamma-nucleotide triphosphate was higher (p < 0.04). There was no significant difference between the two groups in respect of phosphomonoesters, phosphodiesters or broad resonances. Our results are not necessarily inconsistent with the membrane phospholipid hypothesis, given that the patients studied suffered predominantly from positive symptoms of schizophrenia. The results suggest that there is increased cerebral mitochondrial oxidative phosphorylation in patients with schizophrenia who have dangerously and seriously violently offended, with an associated increase in oxygen flux and subsequent electron 'leakage' from the electron transport chain leading to the formation of superoxide radicals and other reactive oxygen species. In turn, these reactive species might cause increased lipid peroxidation in neuroglial membranes, thereby accounting for the observation of increased ethane excretion.

Particulate matter analysis at elementary schools in Curitiba, Brazil

The particulate matter indoors and outdoors of the classrooms at two schools in Curitiba, Brazil, was characterised in order to assess the indoor air quality. Information concerning the bulk composition was provided by energy-dispersive x-ray fluorescence (EDXRF). From the calculated indoor/outdoor ratios and the enrichment factors it was observed that S-, Cl- and Zn-rich particles are of concern in the indoor environment. In the present research, the chemical compositions of individual particles were quantitatively elucidated, including low-Z components like C, N and O, as well as higher-Z elements, using automated electron probe microanalysis low Z EPMA. Samples were further analysed for chemical and morphological aspects, determining the particle size distribution and classifying them according to elemental composition associations. Five classes were identified based on major elemental concentrations: aluminosilicate, soot, organic, calcium carbonate and iron-rich particles. The majority of the respirable particulate matter found inside of the classroom was composed of soot, biogenic and aluminosilicate particles. In view of the chemical composition and size distribution of the aerosol particles, local deposition efficiencies in the human respiratory system were calculated revealing the deposition of soot at alveolar level. The results showed that on average 42% of coarse particles are deposited at the extrathoracic level, whereas 24% are deposited at the pulmonary region. The fine fraction showed a deposition rate of approximately 18% for both deposition levels.

Relationship between oral health status and development of osteoradionecrosis of the mandible: A retrospective longitudinal study

Oral health status is a risk factor for postradiation bone complications (also known as osteoradionecrosis [ORN]), and oral health care is an important element in the prevention of this condition. Some authors recommend extracting teeth with a questionable prognosis and either gross mobility or periodontal disease. However, the criteria for making such decisions remain to be elucidated. In addition, the specific details of the association between oral health status and ORN have not yet been clearly demonstrated. The purpose of this study was to clarify the relationship between oral health status and the development of ORN. Thirty-nine head and neck cancer patients whose radiation fields included both the teeth and the mandible were followed for > or = 3 years after radiotherapy. Among these patients, 6 suffered from ORN (ORN group), and the other 33 did not experience the condition (non-ORN group). We analyzed the patient factors, radiation factors, and oral health factors related to the complication. The onset of ORN occurred from 18 months to 51 months after radiotherapy. The radiation dose in the oral cavity and the oral health status before radiotherapy were not significant risk factors for ORN. However, the oral health status at 1 year or 2 years after radiotherapy was significantly associated with the development of ORN. The oral health conditions that increased the risk of ORN were > 5 mm periodontal pocket depth, > 40% dental plaque score, > 60% alveolar bone loss level, and a grade 3 radiographic periodontal status. This is the first report to show the changes in the oral health status before and after radiotherapy regarding the development of ORN. The results support the periodontal status that almost all clinicians agree on as indications for preradiation teeth extraction (namely, periodontal pockets of > 5 mm) to prevent ORN. Good oral health status, especially after radiotherapy, is very important in the prevention of ORN, and we recommend periodical dental management and care by well trained dentists and dental hygienists to avoid the condition.

HEMORRHAGE PROGRESSIVELY DISTURBS INTERALVEOLAR PERFUSION IN THE LUNGS OF RATS

Acute hemorrhage is often followed by devastating lung injury. However, why blood loss should lead to lung injury is not known. One possibility is that hemorrhage rapidly disturbs the distribution of microvascular perfusion at the alveolar level, which may be a triggering event for subsequent injury. We showed previously that a 30% blood loss in rats caused significant maldistribution of interalveolar perfusion within 45 min (J Trauma 60:158, 2006). In this report, we describe results of further exploration of this phenomenon. We wanted to know if perfusion distribution was disturbed at 15 min, when vascular pressures were significantly reduced by the blood loss, compared with those at 45 min, when the pressures had returned substantially toward normal. We hemorrhaged rats by removing 30% of their blood volume. We quantified interalveolar perfusion distribution by statistically analyzing the trapping patterns of 4-microm-diameter fluorescent latex particles infused into the pulmonary circulation 15 (red particles) and 45 min (green particles) after blood removal. We used confocal fluorescence microscopy to digitally image the trapping patterns in sections of the air-dried lungs and used pattern analysis to quantify the patterns in tissue image volumes that ranged from 1,300 alveoli to less than 1 alveolus. LogDI, a measure of perfusion maldistribution, increased from 1.00 +/- 0.15 at 15 min after blood loss to 1.62 +/- 0.24 at 45 min (P < 0.001). These values were 0.86 +/- 0.22 (15 min) and 1.12 +/- 0.24 (45 min) in control rats (P = 0.03). Hemorrhage caused the green (45 min)-to-red (15 min) particle distance to decrease from 35.9 +/- 6.5 to 28.0 +/- 5.1 microm (P = 0.024) and the red-to-green particle distance to remain unchanged (30.2 +/- 5.7 microm [red]; 31.5 +/- 10.0 microm [green] [n.s.]). We conclude that hemorrhage caused a progressive increase in interalveolar perfusion maldistribution over 45 min that did not correspond to reduced arterial pressures or altered blood gases. Our particle distance measurements led us to further conclude that this maldistribution occurred in areas that were perfused at 15 min rather than in previously unperfused areas .

Zinc deficiency suppresses alveolar macrophage function in in vivo models of both chronic alcohol ingestion and HIV‐1 transgenic expression

Alcohol abuse and HIV‐1 infection independently affect many individuals and render them susceptible to severe pulmonary infections. Alcoholics and HIV‐1 infected individuals are known to be deficient in immunostimulatory micronutrient zinc. Although zinc deficiency is known to have adverse effects on the ciliated epithelium within the upper airway, there is very little known about zinc homeostasis within the alveolar space. In this study, we separately examined alveolar zinc levels and the effect of inadequate zinc microenvironment on alveolar macrophage immune function in chronic alcohol‐fed and hemizygous NL4‐3Δgag/pol transgenic rats. Alveolar epithelial lining fluid from each rat model was significantly zinc deficient. Alveolar macrophages from these rats had significantly fewer granulocyte‐macrophage colony stimulating factor (GM‐CSF) receptors, and significantly reduced capacity to phagocytose bacteria. Zinc supplementation increased pulmonary zinc levels, GM‐CSF receptor expression, and significantly improved phagocytic function of alveolar macrophages in both the models. These data suggest an important role for pulmonary zinc in these two clinical settings that are associated with pneumonia.

HIV-1–Transgene Expression in Rats Decreases Alveolar Macrophage Zinc Levels and Phagocytosis

HIV-1 infection impairs alveolar macrophage immune function and renders patients susceptible to pneumonia by poorly understood mechanisms. Alveolar macrophage maturation and function depends on granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced and secreted by the alveolar epithelium. Macrophages respond to GM-CSF through the GM-CSF receptor (GM-CSFR), which has a binding subunit (GM-CSFRalpha) and a signaling subunit (GM-CSFRbeta). In this study, we measured GM-CSFR expression and alveolar macrophage function in a transgene HIV-1 rat model (NL4-3Delta gag/pol); this construct bears a pro-virus with gag and pol deleted, but other HIV-1-related proteins, such as gp120 and Tat, are expressed, and the rats develop an AIDS-like phenotype as they age. We first determined that HIV-1-transgenic expression selectively decreased alveolar macrophage expression of GM-CSFRbeta and impaired bacterial phagocytosis in vitro. Next, we examined the role of zinc (Zn) deficiency as a potential mechanism underlying these effects, and determined that HIV-1-transgenic rats have significantly lower levels of Zn in the alveolar space and macrophages. To test the direct effect of Zn deficiency on macrophage dysfunction, we treated rat alveolar macrophage cell line with a Zn chelator, N,N,N',N'-tetrakis-(2-pyridyl-methyl) ethylenediamine, and this decreased GM-CSFRbeta expression and phagocytosis. In parallel, treatment with Zn acetate in vitro for 48 hours restored intracellular Zn levels and phagocytic function in alveolar macrophages from HIV-1-transgenic rats. Taken together, these data suggest that pulmonary Zn deficiency could be one of the mechanisms by which chronic HIV-1 infection impairs alveolar macrophage immune function and renders these individuals susceptible to serious lung infections.

Elevated pulmonary dead space and coagulation abnormalities suggest lung microvascular thrombosis in patients undergoing cardiac surgery

Inflammation has been shown to trigger microvascular thrombosis. Patients undergoing cardiac surgery sustain significant inflammatory insults to the lungs and in addition are routinely given anti-fibrinolytic agents to promote thrombosis. In view of these risk factors we investigated if evidence of pulmonary microvascular thrombosis occurs following cardiac surgery and, if so, whether a pre-operative heparin infusion may limit this. Double-blind randomised controlled trial. Tertiary university affiliated hospital. Twenty patients undergoing elective cardiac surgery. Patients were randomised to receive a pre-operative heparin infusion or placebo. All patients were administered aprotinin. Pulmonary microvascular obstruction was estimated by measuring the alveolar dead-space fraction. Pulmonary coagulation activation was estimated by measuring the ratio of prothrombin fragment levels in radial and pulmonary arterial blood. Systemic tissue plasminogen activator (t-PA) levels were also assessed. In the placebo group cardiac surgery triggered increased alveolar dead-space fraction levels and the onset of prothrombin fragment production in the pulmonary circulation. Administration of pre-operative heparin was associated with a lower alveolar dead-space fraction (p < 0.05) and reduced prothrombin fragment production in the pulmonary circulation (p < 0.05). Pre-operative heparin also increased baseline t-PA levels (p < 0.05). The changes in the alveolar dead-space fraction and pulmonary coagulation activation suggest that pulmonary microvascular thrombosis develops during cardiac surgery and this may be limited by a pre-operative heparin infusion.

Pharmacological Intervention to the Inflammatory Response from Decompression Sickness in Rats

Venous bubbles resulting from experimental decompression sickness (DCS) may cause an inflammatory-like reaction with activation of granulocytes and release of metabolites from arachidonic acid. The release of cyclooxygenase and lipoxygenase pathway mediated metabolites, namely thromboxane B2 (TXB2) and leukotriene E4 (LTE4) likely contribute to this overall DCS response. In the present study we examined the effect on DCS outcome of several agents affecting both pathways. Indomethacin and acetylsalicylic acid were administered to study the cyclooxygenase pathway mediators, Zafirlukast and Zileuton to study inhibition of the lipoxygenase pathway, and isoproterenol for its beta-agonist effects. The agents were administered to randomly selected Sprague-Dawley rats prior to compression to 683 kPa for 60 min. Following 60 min recovery post-decompression, DCS evaluation included: gross symptoms; pulmonary edema; bronchoalveolar lavage and pleural fluid protein; white blood cell and differential cell counts; and urine, bronchoalveolar lavage, and plasma TXB2 and LTE4 analysis. The results indicate that both Zafirlukast and Zileuton reduced the reported DCS symptoms, pulmonary edema, pleural and bronchoalveolar lavage protein levels, white blood cell counts in the pleural and bronchoalveolar lavage, and leukotriene levels in the bronchoalveolar lavage vs. that of vehicle-treated rats exposed to compression/decompression. The effect of these agents on pleural and bronchial alveolar protein levels demonstrated protective effects on microvascular permeability. Acetylsalicylic acid and indomethacin treatment had less effect on reducing inflammatory-induced changes. The effect of inflammatory-like responses to DCS can be altered with pharmacological intervention given prior to compression.

Crown lengthening for altered passive eruption

Purpose: Passive eruption is characterized by the apical shift of the dentogingival junction. As this occurs, the length of the clinical crown increases as the epithelial attachment migrates apically. Altered passive eruption occurs when the margin of gingiva is malpositioned incisally on the anatomic crown in adulthood and results in excessive gingiva. The purpose of this article is to evaluate esthetic results of crown lengthening procedure in altered passive eruption.s. Materials and Methods: Three patients who complained My front teeth look too short were included. Bone sounding with periodontal probe revealed that alveolar bone crest was close to CEJ. Based on the diagnostic information, a diagnosis of altered passive eruption was made. They were performed apically positioned flap procedure with osseous resection. Results: Six months later, all patients achieved favorable esthetic results and gingival margins were healthy and stable. Conclusion: When the diagnostic procedures reveal alveolar bone crest levels approximating the CEJ, apically positioned flap procedure with osseous resection is indicated. (J Korean Acad Periodontol 2008;38:247-252)

A phase 1 trial of nebulised heparin in acute lung injury

IntroductionAnimal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI.MethodsAn open label phase 1 trial of four escalating doses of nebulised heparin was performed. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second group 100,000 U/day, the third group 200,000 U/day and the fourth group 400,000 U/day. Assessments of lung function included the PaO2/FiO2 ratio, lung compliance and the alveolar dead space fraction. Monitoring of anticoagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time. Bronchoalveolar lavage fluid was collected and the prothrombin fragment and tissue plasminogen activator levels were assessed. Analysis of variance was used to compare the effects of dose.ResultsNo serious adverse events occurred for any dose. The changes over time for the PaO2/FiO2 ratio, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and thrombin clotting time levels was present with higher doses (P = 0.09 and P = 0.1, respectively). For the highest dose, the APTT reached 64 seconds; following cessation of nebulised heparin, the APTT fell to 39 seconds (P = 0.06). In bronchoalveolar lavage samples a trend to reduced prothrombin fragment levels was present with higher doses (P = 0.1), while tissue plasminogen activator levels were similar for all doses.ConclusionAdministration of nebulised heparin to mechanically ventilated patients with ALI is feasible. Nebulised heparin was not associated with any serious adverse events, and at higher doses it increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anticoagulant effects.Trial registrationAustralian Clinical trials registry ACTRN12606000388516.

Children's Response to Air Pollutants

It is important to focus on children with respect to air pollution because (1) their lungs are not completely developed, (2) they can have greater exposures than adults, and (3) those exposures can deliver higher doses of different composition that may remain in the lung for greater duration. The undeveloped lung is more vulnerable to assault and less able to fully repair itself when injury disrupts morphogenesis. Children spend more time outside, where concentrations of combustion-generated air pollution are generally higher. Children have higher baseline ventilation rates and are more physically active than adults, thus exposing their lungs to more air pollution. Nasal breathing in adults reduces some pollution concentrations, but children are more typically mouth-breathers—suggesting that the composition of the exposure mixture at the alveolar level may be different. Finally, higher ventilation rates and mouth-breathing may pull air pollutants deeper into children's lungs, thereby making clearance slower and more difficult. Children also have immature immune systems, which plays a significant role in asthma. The observed consequences of early life exposure to adverse levels of air pollutants include diminished lung function and increased susceptibility to acute respiratory illness and asthma. Exposure to diesel exhaust, in particular, is an area of concern for multiple endpoints, and deserves further research.

Community-Acquired Pneumonia in Alcoholic Patients

In Brief Recent reports have identified alcoholism to have an important public health impact and cause a substantial loss of lives worldwide. For a long time alcoholism has been identified to favor pulmonary infections. But only in the last 2 decades the alterations induced by ethanol to the complex mechanisms of lung defense have been recognized. Alcohol alters lung defenses on all levels. It is known to favor oropharyngeal colonization by potentially pathogenic bacteria, aspiration by altering the cough reflex, and to decrease ciliary motility and surfactant production. Innate and adaptive immune responses on the systemic and alveolar level are compromised by alteration of cytokines, decreased chemotaxis, and phagocytic activity of alveolar macrophages and neutrophils. Recent data suggest that Streptococcus pneumoniae is the leading pathogen responsible for community-acquired pneumonia in alcoholic patients. However, series have reported Klebsiella pneumoniae, Legionella pneumophilia, and other Gram-negative enterobacteriaceae to be frequent, especially in severe cases. Anaerobes may play a role if aspiration after acute intoxication is the cause. The clinical course of community-acquired pneumonia in alcoholic patients is more severe leading to more intensive care unit care, longer hospital stay, and a delay of clinical improvement after initiation of therapy. Convincing data are available showing a predisposition of alcoholic patients for the development of acute respiratory distress syndrome. Some issues still remain controversial as to the rate of multiresistant bacteria or an increased mortality. Regarding the treatment of alcoholic patients, particularities and potential modifiers of antimicrobial treatment have to be accounted for. These include other frequent comorbid conditions such as chronic obstructive pulmonary disease and liver disease, complex socioeconomic and psychiatric conditions, and poor adherence to therapy. For a long time alcoholism has been identified to favor pulmonary infections. But only in the last 2 decades the alterations induced by ethanol to the complex mechanisms of lung defense been recognized. The following review provides an overview of the pathophysiology, epidemiology, and particular clinical aspects of community-acquired pneumonia in alcoholic patients.

A Novel Inhibitor of Inducible Nitric Oxide Synthase, ONO-1714, Does Not Ameliorate Hypoxia-induced Pulmonary Hypertension in Rats

A recent study showed that long-term administration of the inducible nitric oxide synthase (iNOS) inhibitor L-NIL reduced the development of pulmonary hypertension. The purpose of the present study was to identify the effect of an another iNOS inhibitor, ONO-1714, on the development of pulmonary hypertensive vascular changes in chronic hypoxic pulmonary hypertension in rats. ONO-1714 was administered to rats exposed to hypobaric hypoxia (air at 380 mmHg) for 10 days. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. iNOS mRNA and protein levels of the lung were assessed in normal and hypoxic rats. Chronic hypoxia induced pulmonary hypertension, right ventricular hypertrophy, and hypertensive pulmonary vascular changes. Although an acute single injection of ONO-1714 induced a significant increase in mean pulmonary artery pressure in chronic hypoxic pulmonary hypertensive rats, the increase was slight and transient. There were no significant differences among rats with and without long-term administration of ONO-1714 in pulmonary artery pressure, right ventricular hypertrophy, medial wall thickness of muscular arteries, and the percentage of muscularized arteries at the alveolar wall and duct levels. Although there was a significantly increased expression of iNOS as assessed with the reverse-transcription polymerase chain reaction in rats that were exposed to 10 days of hypobaric hypoxia, we could not detect a significant level of iNOS protein by Western blotting. ONO-1714 does not have a therapeutic role in preventing the development of chronic hypoxic pulmonary hypertension.