Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The technique of high-frequency oscillatory ventilation (HFOV) was successfully used in a preterm infant with severe hyaline membrane disease and in a term neonate presenting with intrauterine pneumonia and associated severe pneumomediastinum. None of the infants could adequately be ventilated by conventional ventilation; both of them deteriorated owing to severe hypoxaemia and hypercapnia. In the preterm infant with HMD a rapid and progressive improvement of oxygenation had been observed immediately after the beginning of HFOV, and he was successfully weaned off the ventilator after 71 hours on HFOV. His recovery was uncomplicated and definitive. In the term neonate presenting with IUP and associated severe PM, an improvement in oxygenation was detected, whereas the retention of paCO2 remained unaltered. On leaving the MAP unchanged but doubling the flow rate, paCO2 and arterial pH also normalised. No sign of PM was seen on the X-ray picture 17.5 hours after the start of HFOV. This patient was weaned off the ventilator after 29 hours on HFOV and his recovery was also uncomplicated. It is believed that recovery of the PM was secondary to the low MAP and to the higher arterial pO2 levels, and that HFOV may also have a direct role in the treatment of preexisting air leaks and perhaps also in their prevention. In our patients HFOV resulted in a definitive recovery, while no improvement had occurred on using conventional ventilation. To determine the exact mechanism of action, the clear cut fields of indications and the possible side effects of HFOV, further investigations are needed.
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PMID:High-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory disturbances: case reports of two infants. 393 21

By pediatricians the high frequency oscillatory ventilation (HFOV) is used almost only in the neonatal period. We report on the administration of HFOV in infants with pulmonary insufficiency after failure of conventional ventilatory support. 6 infants (aged 2-7 months, all former preterm babies) were referred to our hospital due to severe pneumonia after unsuccessful conservative management. Indications for HFOV were hypoxia (mean paO2 41.8 mm Hg with FiO2 = 0.95 and mean airway pressure = 16.6 cm H2O) and/or air leak syndrome. In all cases a sufficient oxygenation could be achieved by HFOV, followed then by stepwise reduction of FiO2 and MAP. The air leaks receded. After 12-178 h on HFOV a successful switchback to conventional ventilatory support (at FiO2 = 0.48 and MAP < 12 cm H2O) was possible, all infants were extubated 6-15 days later. Possible risks of HFOV are air leaks, a necrotizing tracheobronchitis and hemodynamic changes due to compression of the heart and great vessels. With the at the moment in Germany available oscillatory ventilators HFOV as a rescue therapy must be limited for infants with a body weight below 5-6 kg.
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PMID:[High frequency oscillatory ventilation of infants with severe respiratory disorders: possibilities, risks and limits]. 805 9

Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.
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PMID:Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity observed in a rat model of acute Pseudomonas pneumonia. 876 59

Sepsis is one of the most frequent causes of death after major burn injury. Usually, sepsis appears as a consequence of a gram-negative bacteriaemia with release of endotoxins. In this study, the plasma endotoxin levels of seven patients (three female, four male; average age 51.3 +/- 23.8 years) with burns between 43.5 and 78 % Total Body Surface Area (Abbreviated Burn Severity Index 8 - 12) were determined for five days after thermal trauma every three hours by ELISA and compared with the concentration of procalcitonin (PCT) and C-reactive protein (CRP). A calculation of the Horrowitz-Index (PaO(2)/FiO(2)) and the Pressure-Adjusted Heart Rate (HR x CVP/MAP) took place to show a possible correlation between the endotoxin concentration and the cardiopulmonary organ function. Additionally, we analysed whether operative treatment can influence the level of plasma endotoxin in the early phase after burn injury. At any time after burn trauma, endotoxins could be detected in the plasma of all patients. Between the second and third day, there was a considerable increase in the endotoxin concentration with a maximum after 57 hours of 0.48 +/- 0.32 EU/ml. Two patients with sepsis and death in the further course had a rather distinctive increase. From the fourth day on, occasional episodes of increases in endotoxin concentration were noted. Postoperatively, there was a short increase in plasma endotoxin on the second and fourth day. The plasma endotoxin level showed no correlation with the PCT and CRP or with the oxygenation in the patients' blood. However, a positive correlation could be observed with the Pressure-Adjusted Heart Rate (p = 0.0061; r(2) = 0.212). An explanation for the endotoxin increase after 57 hours could be the translocation of intestinal bacteria, the beginning of bacterial colonisation or decomposition products of the burn wound with protein-protein complexes. Later on, infectious diseases such as pneumonia with gram-negative bacteria are of importance, too. According to the Two-Hit Model, the increase of plasma endotoxin can serve as a trigger and cause a recurrence of systemic inflammation with the changes observed in cardiac organ function, multiple organ dysfunction, and multiple organ failure.
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PMID:[Plasma endotoxin, procalcitonin, C-reactive protein, and organ functions in patients with major burns]. 1151 88

Chlamydiae are obligate intracellular pathogens that replicate within a membrane-bound compartment (the inclusion) and are associated with important human diseases, such as trachoma, pneumonia, and atherosclerosis. We have examined the interaction of the host autophagic pathway with Chlamydia trachomatis serovar L2 by using the specific autophagosomal stain monodansylcadaverine, antibodies to autophagosome-associated markers, and traditionally used autophagic inhibitors, particularly 3-methyladenine and amino acids. Chlamydial inclusions did not sequester monodansylcadaverine, suggesting absence of fusion with autophagosomes. Interestingly, exposure of cultures infected for 19 h to 3-methyladenine or single amino acids until the end of infection (44 h) caused various degrees of abnormalities in the inclusion maturation and in the progeny infectivity. Incubation of host cells with chemicals throughout the entire period of infection modulated the growth of Chlamydia even more dramatically. Remarkably, autophagosomal markers MAP-LC3 and calreticulin were redistributed to the inclusion of Chlamydia, a process that appears to be sensitive to 3-methyladenine and some amino acids. The present data indicate the lack of autophagosomal fusion with the inclusion because it was devoid of monodansylcadaverine and no distinct rim of autophagosomal protein-specific staining around the inclusion could be observed. However, high sensitivity of Chlamydia to conditions that could inhibit host autophagic pathway and the close association of MAP-LC3 and calreticulin with the inclusion membrane still suggest a potential role of host autophagy in the pathogenesis of Chlamydia.
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PMID:Interaction of Chlamydia trachomatis serovar L2 with the host autophagic pathway. 1527 37

Programmed death of peripheral blood mononuclear cells from donors with acute inflammatory diseases (an acute appendicitis, a community-acquired pneumonia) was investigated under condition of oxidative stress in vitro and under effect of selective inhibitors of MAP-kinases JNK and p38. Levels of active and inactive forms of MAP-kinases, and factors of transcription were determined by immunoblotting (western blot analysis). The increase in the activity of apoptosis under condition of oxidative stress in vivo and during the acute inflammatory diseases is associated with the increase in the level of reactive oxygen species (ROS) in the cells. The action of inhibitors of MAP-kinases JNK (SP600125) and p38 (ML3403) in vitro under condition of oxidative stress prevents increase in the quantity of annexin-positive mononuclear leucocytes that testifies to involving JNK and p38 MAP-kinases in apoptosis deregulation oxidative mechanisms. The appearance of NF-kappaB in the mononuclear leucocytes under condition of oxidative stress during the acute inflammatory diseases and at the experiment was shown; p53 was registered only under condition of oxidative stress in vitro. The effect of p53 and NF-kappaB results in the increase in the quantity of apoptosis annexin-positive mononuclear leucocytes that testify to inoperativeness of antiapoptotic regulation NF-kappaB.
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PMID:[The role of redox-dependent signal systems in the regulation of apoptosis under oxidative stress condition]. 1950 51

Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening diseases that are characterized by acute onset, pulmonary inflammation, oedema due to increased vascular permeability and severe hypoxemia. Clinically, ARDS can be divided into ARDS due to direct causes such as pneumonia, aspiration or injurious ventilation, and due to extrapulmonary indirect causes such as sepsis, severe burns or pancreatitis. In order to identify potential therapeutic targets, we asked here whether common molecular mechanisms can be identified that are relevant in different models of the direct form of ALI/ARDS. To this end, we reviewed three widely used models: (a) one based on a biological insult, i.e. instillation of bacterial endotoxins; (b) one based on a chemical insult, i.e. instillation of acid; and (c) one based on a mechanical insult, i.e. injurious ventilation. Studies were included only if the mediator or mechanism of interest was studied in at least two of the three animal models listed above. As endpoints, we selected neutrophil sequestration, permeability, hypoxemia (physiological dysfunction) and survival. Our analysis showed that most studies have focused on mechanisms of pulmonary neutrophil sequestration and models with moderate forms of oedema. The underlying mechanisms that involve canonical inflammatory pathways such as MAP kinases, CXCR2 chemokines, PAF, leukotrienes, adhesions molecules (CD18, ICAM-1) and elastase have been defined relatively well. Further mechanisms including TNF, DARC, HMGB1, PARP, GADD45 and collagenase are under investigation. Such mechanisms that are shared between the three ALI models may represent viable therapeutic targets. However, only few studies have linked these pathways to hypoxemia, the most important clinical aspect of ALI/ARDS. Since moderate oedema does not necessarily lead to hypoxemia, we suggest that the clinical relevance of experimental studies can be further improved by putting greater emphasis on gas exchange.
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PMID:Models and mechanisms of acute lung injury caused by direct insults. 2228 32

Associated with an increase of small-sized lung cancer or metachronous second primary lung cancer, we have more opportunities to perform sublobar resection. Difficulties of identifying tumor location and appropriate surgical margin for small-sized ground-glass opacity (GGO) dominant lesions in thoracoscopic surgery is the big issue of sublobar resection. Virtual-assisted lung mapping (VAL-MAP) that makes markings on the lung surface through some peripheral bronchi by bronchoscopically projects intrapulmonary anatomy on the lung surface and literally draw a map. We report a case of thoracoscopic left upper division segmentectomy for multiple ground-glass nodules (GGNs) using preoperative VAL-MAP. A 65-year-old women who had undergone right upper lobectomy for primary lung cancer, and had multiple GGNs in the bilateral lungs was followed up as an outpatient. Eleven years after initial pulmonary resection, 2 lesions in the left upper division became bigger, and we decided to perform surgery for 4 GGNs in the left upper division including these 2 lesions. We preoperatively made bronchoscopic dye markings through B1+2c, B3a and B4a for in the left upper lobe. The 3 markings were intraoperatively identified. We decided the resection line based on the markings and performed thoracoscopic left upper division segmentectomy. The pathological diagnosis was minimally invasive adenocarcinoma, adenocarcinoma in situ and pneumonitis. Surgical margins were negative. VAL-MAP will assume an important role as an intraoperative navigation system for sublobar resection.
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PMID:[Thoracoscopic Left Upper Division Segmentectomy for Multiple Ground-glass Nodules Using Preoperative Virtual-assisted Lung Mapping]. 3129 3