Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([99Tcm]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (ServoVentilator 900C). VP was either deep slow (f = 20 min-1, tidal volume (VT) = 30 +/- 4 ml kg-1 and positive end-expiratory pressure (PEEP) = 0.2 kPa [VP 20/0.2, n = 8]) or rapid shallow (f = 80 min-1, VT = 11 +/- 2 ml kg-1 and PEEP = 0.2 or 0.4 kPa [VP 80/0.2, n = 6 and VP 80/0.4, n = 6]). The mean airway pressure was similar at VP 20/0.2 and VP 80/0.4. During administration of [99Tcm]DTPA aerosol all animals were ventilated under the same conditions (f = 40 min-1 and PEEP = 0.2 kPa). The pulmonary clearance rate expressed as the half-life time (T1/2) of [99Tcm]DTPA was at VP 80/0.2 = 113 +/- 31 min, at VP 80/0.4 = 70 +/- 24 min (P less than 0.01 compared to VP 80/0.2) and at VP 20/0.2 = 36 +/- 18 min (P less than 0.001 compared to VP 80/0.2 and P less than 0.01 compared to VP 80/0.4). We conclude that the pulmonary clearance of [99Tcm]DTPA increases (1) during rapid shallow ventilation when PEEP is increased from 0.2 to 0.4 kPa; (2) during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.     

Reticular basement membrane thickening in airways of lung transplant recipients is not affected by inhaled corticosteroids

INTRODUCTION: Chronic rejection is a major problem for all lung transplant programmes, which is functionally manifested by fixed airflow limitation, Bronchiolitis Obliterans Syndrome (BOS). The inclusion of a Pre-BOS category, BOS(0 approximately p), in newly revised guidelines, recognizes the potential importance of early changes. We have previously demonstrated reticular basement membrane (Rbm) thickening in clinically stable lung transplant recipients free from BOS. The present study extends this, testing the hypothesis that inhaled corticosteroid (ICS) therapy will lead to a decrease in Rbm thickness in lung transplant recipients. METHODS: A parallel group, bronchoscopic intervention study of clinically stable lung allograft recipients, free from BOS, but with evidence of airway inflammation. Following baseline assessment of Rbm thickening, subjects were randomized to 3 months of either chlorofluorocarbon-driven beclomethasone diproprionate (BDP) 400 microg b.i.d., or a formulation designed to yield at least an equivalent dose, hydrofluoroalkane-driven BDP, 200 microg b.i.d. RESULTS: Three months treatment with a moderate dose of ICS, including a formulation designed for preferential small airway deposition, had no effect on Rbm thickening (13+/-3 vs. 14+/-5 microm post-ICS). CONCLUSION: Our data would suggest that airway remodelling can occur early in lung allografts and is not affected by moderate dose ICS therapy. Longitudinal studies are required to describe the pathophysiological processes involved in BOS, and specifically to elucidate potential relationships between airway remodelling, airflow obstruction and allograft failure.     

内毒素的肺内清除与灭活

本文通过检测正常家兔入、出肺血内毒素含量。家兔肺清除~(51)Cr标记内毒素及观察大鼠先后经过肺注入内毒素的死亡率研究了肺对内毒素的清除与灭活作用。结果表明:正常家兔入肺血内毒素含量明显高于出肺血(P<0.01)。300μg~(51)Cr标记大肠杆菌内毒素一次流经肺循环的肺内清除率为50.31%。静脉注入内毒素组大鼠12及24小时死亡率明显低于动脉注入组(P<0.01和P<0.05)。上述实验结果提示肺可清除循环血中内毒素,内毒素能在肺内灭活。     

Morphometric changes of the lung induced by inhaled bacterial endotoxin

Due to the ubiquitous nature of airborne endotoxin, an understanding of pulmonary alterations which follow inhalation of environmentally realistic concentrations of purified bacteria derived lipopolysaccharide (LPS) is important. Using LPS derived from Enterobacter agglomerans, a bacterium found in cotton and cotton mill dust, aqueous aerosols (effective LPS concentration 4 micrograms/m3) were generated and used to expose either normal hamsters (N = 6) or those rendered endotoxin tolerant by pre-ip injection of 0.1 LD50 LPS. Control groups (normal--N = 6; tolerant--N = 6) received saline aerosol only. At 6 hr after 5-hr aerosol exposure, lungs of all animals were fixed, processed for light and transmission electron microscopy, and subject to qualitative and to multitiered morphometric analysis using standard point counting techniques. Qualitative evaluation of TEM micrographs from LPS aerosolized-nontolerant hamsters showed endothelial alteration (focal disruption, subendothelial space formation, and cytoplasmic blebbing) but volume and number of endothelial cells were not changed indicating only slight, focal endothelial damage. Quantitatively, septal capillary blood space in nontolerant, LPS aerosolized hamsters showed increased Vv of PMNs and platelets. These changes were not seen in tolerant induced-LPS aerosolized hamsters. Independent of tolerization treatment, LPS inhalation led to a decrease in fixed lung volume and an increase in numerical density of endothelial pinocytotic vesicles. It is concluded that the inhalation of realistic, environmental levels of bacterial endotoxin may induce significant changes in distal lung and may be important in the pathogenesis of byssinosis and adult respiratory distress syndrome.     

Reperfusion pulmonary edema after the removal of hepatocellular carcinoma embolus

To report a non-fatal case of reperfusion pulmonary edema (RPE) after the removal of a hepatocellular carcinoma embolus, which had caused an acute obstruction of the tricuspid valve and pulmonary vasculature during a hepatic lobectomy. Pulmonary embolism caused by hepatocellular carcinoma embolus is extremely rare, and, in the present case, it was associated with unusual clinical features. A 69-year-old ASA II woman with hepatocellular carcinoma was presented for an elective left hepatic lobectomy. During the surgery, the tumor embolus was dislodged from the interior of the lumen of the inferior vena cava (IVC), which then drifted into the tricuspid valve area and pulmonary vasculature. The patient showed the specific signs of acute pulmonary embolism, such as a reduction in end-tidal carbon dioxide, an increase in central venous pressure, and a decrease in arterial pressure. The patient exhibited the symptoms for about 10 minutes. After this period, however, cardiovascular variables became relatively stable, even during a mechanical obstruction due to cross-clamping the pulmonary artery for embolectomy. After several hours of pulmonary embolectomy, the patient experienced an episode of RPE. The ventilatory supports for the treatment of RPE were successful, and the patient recovered without any complications. The patient's case in the present study demonstrates that pulmonary embolism may occur as a result of a hepatocellular carcinoma extending into the IVC during operative management. The anesthesiologist should be careful of the possibilities of RPE after removal of the tumor embolus.     

Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity.

Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells (APCs) of the lung, playing a vital role in the induction of cell-mediated immunity to inhaled antigens. We have previously demonstrated that an airway challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of specific antigen-presenting cell activity by purified pulmonary DCs and a cell-mediated immune response in the lung upon secondary challenge. To examine how a particulate antigen leads to a cell-mediated response in vivo, graded concentrations of heat-killed Listeria (HKL) were injected intratracheally into Lewis rats. The bacteria were rapidly ingested by lung macrophages and polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in vivo by an airway challenge with HKL to subsequently stimulate HKL-specific responses ex vivo showed a threshold response, requiring a dose in excess of 10(9) organisms/rat. By contrast, all dosages of HKL yielded specific sensitization of lymphocytes in the draining bilar nodes. Pulmonary DCs purified from rats after a secondary in vivo airway challenge with HKL at day 14 were ineffective antigen-presenting cells except at high dosages of antigen. The generation of cell-mediated pulmonary inflammation paralleled the antigen-presenting cell activity of pulmonary DCs and was observed only at high antigen dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected intratracheally yielded comparable results to those observed with HKL. We suggest that a pulmonary cellular immune response is generated to an inhaled particulate antigen when the protective phagocytic capacities of the lung are exceeded and antigen is able to interact directly with interstitial DCs. The diversion of particulate antigens by pulmonary phagocytes may help to limit undesirable pulmonary inflammation while allowing the generation of antigen-specific immune lymphocytes in vivo.     

Positive end-expiratory pressure increases pulmonary clearance of inhaled 99mTc-DTPA in nonsmokers but not in healthy smokers

Positive end-expiratory pressure (PEEP) is widely used in the treatment of severe pulmonary oedema, although its effects on the clearance of water and small solutes from alveolus to blood are not well characterized. We studied the effect of the application of 10 cmH2O of PEEP on the flux of inhaled 99mTc-diethylene-triamine-penta-acetic acid (DTPA) from lung to blood in six healthy smoking and six nonsmoking subjects. The rate of flux was corrected for possible changes in pulmonary blood volume during PEEP by use of an intravenous injection of 99mTc-DTPA. The baseline clearance rate (K, % X min-1) for nonsmokers was 1.48 +/- 0.12 (mean +/- SE) and increased to 2.40 +/- 0.29 during PEEP (p less than 0.05). In contrast, the mean clearance rate for smokers was 3.26 +/- 0.82 at baseline and 3.03 +/- 0.82 during PEEP (p = NS). The application of positive end-expiratory pressure appears to increase alveolar solute flux in nonsmokers but not in smokers, suggesting that the pathway for solute clearance in smokers is governed by different rate-limiting steps to those of nonsmokers.     

A direct modeling approach to the early renal vascular transit of 99mTc chelates

Delay channel integral methods are developed and applied for analyzing human renal scintiangiographic data produced after peripheral venous injection of a 99mTc chelete. The results include information for two renal vascular compartments (C1, C2) and a residual compartment (Cr). Each vascular compartment is associated with a fraction of the total renal plasma flow (A1, A2) and a mean transit time (T1, T2). The residual compartment has the residual plasma flow fraction Ar. The results obtained in 40 normal kidneys are presented and compared theoretically to the results from other methods.     

Vascular leiomyoma of the lung arising from pulmonary artery

Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author’s best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 x 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation.     

An Association of Prior Therapeutic Chest Irradiation and 99mTc Pyrophosphate Uptake in the Heart

The effect of ionizing radiation on the heart is well known, however, the exact magnitude of cardiac involvement in patients undergoing therapeutic radiation directed to or near the heart is not known. Current tests (ie, serum enzymes [SGPT, SGOT, CPK]) to assess cardiac damage are quite insensitive. With the availability of ^99mTc pyrophosphate for myocardial imaging, a population of 70 subjects who had prior irradiation, 32 to the left chest, 38 elsewhere to the body, were evaluated by pyrophosphate imaging with bone scans.     

核素^99mTc—DTPA测定GFR与公式估算GFR的相关性研究

目的：探讨核素^99mTc—DTPA测定GFR与MDRD公式、简化MDRD公式估算GFR的相关性。方法：178例CKD患者，用核素^99mTc—DTPA测定GFR，同时测定血清肌酐、尿素氮和白蛋白，根据年龄和性别分别用MDRD和简化MDRD公式估算GFR。结果：核素^99mTc—DTPA测定的GFR与MDRD公式估算的GFR有显著性差异，P=0．0001，MDRD公式高估了GFR；核素^99mTc—DTPA测定的GFR与简化MDRD公式估算的GFR亦有显著性差异，P=0．0001，简化MDRD公式低估了GFR；MDRD公式估算的GFR与核素^99mTc—DTPA测定的GFR呈正相关，r=0．8292，P〈0．01；简化MDRD公式估算的GFR与核素^99mTc—DTPA测定的GFR值呈正相关，r=0．8277，P〈0．01。结论：MDRD公式、简化MDRD公式估算的GFR与核素^99mTc—DTPA测得的GFR有差异，需进一步校正后用于估算GFR。     

Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions

A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIR(sur)) and volumetric (DIR(vol)), and two metrics: Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. V(HU) resulted in statistically significant differences for both DIR(sur) (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIR(vol) (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, V(Jac) resulted in non-significant differences for both DIR(sur) (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIR(vol) (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.     

Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice.

We evaluated the effects of anti-inflammatory drugs in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Mice instilled with 100 micrograms of Aspergillus fumigatus antigen (intranasally, 3 days a week for 3 weeks) developed pulmonary lesions, characterized by a perivascular and peribronchial eosinophil infiltration, a bronchoalveolar lavage (BAL) eosinophilia, and elevated levels of total IgE, total IgG1 and A. fumigatus-specific IgG1. Under the same conditions, groups of mice receiving a daily dose of 2 mg/kg dexamethasone showed decreased numbers of eosinophils and total cells in BAL, had less numerous eosinophils in their pulmonary infiltrates, and had lower levels of serum and BAL fluid total IgE, total IgG1 and A. fumigatus-specific IgG1. Conversely, groups of mice pretreated with an immunosuppressive agent, cyclosporin A (CsA) at a dose of 50 mg/kg, three times per week, developed pulmonary lesions with enhanced lung eosinophilic influx and increased total IgE levels, both in serum and in BAL fluid. These findings show that dexamethasone potently prevents the murine immunopathologic response to A. fumigatus. The effect of CsA on this inflammatory response was paradoxical, insofar as it suggests an activation of the T helper 2 subset, which up-regulates eosinophil recruitment and IgE production.     

Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens

Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial-limbic-paralimbic-associative cortical dementias (Alzheimer's disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal "spot" for explicit symbols. (14) "Psychiatric syndromes": metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive-compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget's disease: bones for bipedal gait and cranium. Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.     

正常及内毒素性休克时胆囊收缩素的肺内清除

应用￣（１２５）标记８肽的胆囊收缩素（ＣＣＫ一８）和￣（５１Ｃｒ标记兔红细胞一次通过肺循环的方法，研究了正常和内毒素性休克（ＥＳ）家兔肺对ＣＣＫ的清除作用。结果表明，ＥＳ组肺循环时间延长，心输出量减少，肺对ＣＣＫ一８的清除率正常组平均为３８．９５±３．０％，ＥＳ组为３０．８６±６．２４％（ｘ＋ｓ），有非常显著性差异（Ｐ＜０．０１）。提示在ＥＳ时家兔肺清除ＣＣＫ减少。