Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A collaborative study was performed to determine the different types and mechanisms of intestinal abnormalities during gestation. Cases had to fulfill one or more of the following three criteria: (1) meconium ileus, (2) intestinal stenosis or atresia, and (3) meconium peritonitis. Esophageal atresia, anorectal atresia, and abdominal wall defects were excluded. One hundred two cases were reviewed from the autopsies of 42 induced abortions, 22 stillborns, and the surgical findings in 38 neonates. Meconium ileus was detected mainly during the second trimester (28/38), and was associated with cystic fibrosis (15), fetal blood deglutition (4), infection (6), or multiple-abnormalities (10), in which three chromosomal aberrations were found. Intestinal stenosis or atresia was more commonly detected during the third trimester of gestation (46/56). Sixteen of the 30 duodenal malformations were associated with trisomy 21, whereas in the 26 small intestinal atresias, signs of distress or ischemia were most frequently detected. Only 8 of 25 meconium peritonitis cases were isolated. A total of 20 cystic fibrosis cases could be proved. In this series, functional abnormalities were observed predominantly in the second trimester and associated mainly with cystic fibrosis or amniotic fluid abnormalities. Anatomic lesions were commonly detected later on and associated with ischemic conditions, chromosomal aberrations, and even cystic fibrosis.
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PMID:Meconium ileus and intestinal atresia in fetuses and neonates. 896 29

This review illustrates the changing paradigms in the understanding of the pathogenesis of pneumatosis intestinalis. Although many theories have been evoked, pragmatically there appear to be four major clinical and diagnostic imaging considerations. The most common and most emergent life-threatening cause of intramural bowel gas is the result of bowel necrosis due to bowel ischemia, infarction, necrotizing enterocolitis, neutropenic colitis, volvulus, and sepsis. In the stomach, intramural gas can be caused by emphysematous gastritis or ingestion of caustic agents. These situations represent surgical emergencies. Pneumatosis is found secondary to mucosal disruption presumably due to over-distention from peptic ulcer, pyloric stenosis, annular pancreas, and even to more distal obstruction. Disruption can also be caused by ulceration, erosions, or trauma, including the trauma of child abuse. Disruption can also be iatrogenic from intracatheter jejunal feeding tubes, stent perforation, sclerotherapy, or surgical or endoscopic trauma. In these cases, the gas may be focal or linear. Treatment depends on the extent of the disruption and the underlying cause. A more subtle form of mucosal disruption may occur due to mucosal erosions and also to defects in intestinal crypts secondary to acute and subclinical enteritides that allow intraluminal bacterial gas under pressure to percolate into the bowel wall layers, particularly the submucosa (29). Pneumatosis, often linear or cystic in appearance, is seen with increased frequency in patients who are immunocompromised because of steroids, chemotherapy, radiation therapy, or AIDS. In these cases, the pneumatosis may result from intraluminal bacterial gas entering the bowel wall due to increased mucosal permeability caused by defects in bowel wall lymphoid tissue. Clinical and imaging findings are important in the differentiation of this transient pneumatosis from fulminant life-threatening causes in this subset of patients. A pulmonary cause must still be considered in cases of chronic obstructive pulmonary disease, asthma, and cystic fibrosis. It can occur with barotrauma and after chest tube placement. It may relate to increased intrathoracic pressure associated with retching and vomiting. The possibility remains that occasionally the origin of pneumatosis intestinalis will remain cryptogenic--caused but unexplained.
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PMID:Pneumatosis intestinalis: a review. 953 Feb 94

We report a case of massive endobronchial hemorrhage following a fistula formation of the right pulmonary artery to the right mainstem bronchus in a 15-year-old girl. The fistula had occurred 39 days after the patient had undergone bilateral lung transplantation for cystic fibrosis. The post-transplantation course was remarkable for bronchial colonization by Aspergillus at the site of right bronchial anastomosis and an episode of spontaneous, self-limited hemoptysis on postoperative day 17. A massive endobronchial hemorrhage during surveillance bronchoscopy occurred 39 days after transplantation. Immediate intervention, including rigid bronchoscopy followed by surgery, was effective in saving the patient. The pathophysiologic hypothesis to explain the fistula of the right pulmonary artery to the right mainstem bronchus probably involves ischemia of the anastomosis with necrosis of the suture zone complicated by endobronchial infection with Aspergillus. Rigid bronchoscopic intervention associated with an excellent medical surgical collaboration was pivotal in successfully rescuing the patient.
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PMID:Management of an intrabronchial rupture of right main pulmonary artery: a case report. 1188 88

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
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PMID:Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. 1278 86

Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.
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PMID:Sodium 4-phenylbutyrate protects against cerebral ischemic injury. 1522 15

Lung transplantation (LT) under urgency-code mechanical ventilation (UCMV) has been identified in the International Society for Heart and Lung Transplantation (ISHLT) Registry as a negative prognostic factor increasing the likelihood of mortality. The objective of this study was to review our experience of UCLT for with cystic fibrosis (CF) patients compared with elective LT (ELT). From October 1993 to October 2007, we performed 259 consecutive LTs in 250 patients, of whom 78 (31.20%) had CF. Our study group comprised CF patients who received UCLT (n = 23). The type of LT in the UCLT group was as follows: bipulmonary (18), left unipulmonary (2), and bilobar transplantation from cadavers (3). The UCLT group more often required cardiopulmonary bypass (CB) (P = .025), pulmonary tailoring (P = .030), and longer periods of pulmonary ischemia (P = .066) than the ELT group. We noticed a greater number of cases of pneumonia during the first postoperative month in the UCLT group. However, incidence of surgical complications, early and perioperative mortality, and episodes of acute and chronic rejection (bronchiolitis obliterans syndrome) did not differ between the groups. Survival rates at 1, 3, 5, and 10 years were 73.66%, 63.74%, 42.49%, and 42.49%, respectively, in the UCLT group (mean, 1927 [SE = 366] days) and 75.95%, 71.32%, 63.37%, and 63.37% in the ELT group (mean, 2946 [SE = 281] days; P = .3417). In our experience, UCLT in patients with CF is fully justified. Careful selection of such cases permits acceptable long-term survival rates to be achieved with no increase in early or perioperative mortality.
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PMID:Urgency-code lung transplantation for cystic fibrosis: experience and results. 1901 Jan 96

As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.
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PMID:Disruption of iron homeostasis and lung disease. 1910 Mar 11

Lung transplantation (LT) is a recognized procedure for selected patients with end-stage respiratory failure. We performed 123 LT, including 32 single lung, 84 double lung, and 7 heart-lung transplantations in 48 patients with chronic obstructive pulmonary disease (COPD), 13 patients with pulmonary hypertension (PH), 33 with cystic fibrosis (CF), and 29 with interstitial lung disease (ILD) between July 1990 and January 2008. Survival was compared for periods before and after December 2001. The mean age of patients was 44.4 years (range 16-66.5 years); 84 (69%) were men. Before LT, 1 second forced expiratory volume was 28.7% +/- 18.1% and PaCO(2) = 6.3 kPa. Fifty-five patients were on noninvasive ventilation. Cold ischemia time was 320 +/- 91 minutes. Cardiopulmonary bypass (CPB) was used in 77 patients (64%). There were 18 early surgical reinterventions, 8 extracorporeal membrane oxygenations, and 38 bronchial stent insertions among 206 at-risk bronchial sutures. Crude survivals were 69%, 58%, 41%, and 18% at 1, 2, 5, and 10 years, respectively. Comparing before (n = 70 with 15 CF) vs after December 2001 (n = 53 with 17 CF), survivals were 63% vs 78%, 51% vs 71%, and 33% vs 60% at 1, 2, and 5 years, respectively (P = .01) and for CF patients, 52% vs 100%, 52% vs 94%, and 25% vs 94% at 1, 2, and 5 years, respectively (P = .005). There was significant improvement in survival before and after 2001 in 123 LT and particularly among CF patients. Improvement in survival after LT may be related to the sum of numerous changes in our practice since December 2001, including the use of pulmonary rehabilitation pre-LT, extracellular pneumoplegia, statins, macrolides for chronic rejection, monitoring of Epstein-Barr blood load, changes in maintenance immunosuppressants, as well as position movement up the coordinator nurse and learning curve.
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PMID:Dramatic improvement in survival after lung transplantation over time: a single center experience. 1932 57

Heterocyclic indazole derivatives are claimed in patent WO2008138448 as inhibitors of the serum- and glucocorticoid-inducible-kinase 1 (SGK1) and drugs for the pharmacological treatment of SGK1-related diseases, such as diabetes, obesity, metabolic syndrome, systemic and pulmonary hypertension, cardiac fibrosis, hypertrophy and insufficiency, arteriosclerosis, glomerulosclerosis, nephrosclerosis, nephritis, nephropathy, deranged electrolyte excretion, fibrosing and inflammatory disease (e.g., liver cirrhosis, lung fibrosis, rheumatism, arthrosis, Crohn s disease, chronic bronchitis, radiation fibrosis, sclerodermia, cystic fibrosis, scar formation and Alzheimer' disease), tumor growth, peptic ulcers and some disorders hitherto not conclusively shown to involve SGK1. Most of the claims are supported by the literature. SGK1 is ubiquitously expressed and its expression is stimulated by hyperglycemia, cell shrinkage, ischemia, glucocorticoids, mineralocorticoids and several inflammatory mediators including TGF-ss. SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway. SGK1 regulates ion channels (including ENaC, KCNE1/KCNQ1), carriers (including NCC, NHE3, SGLT1), Na(+)/K(+)-ATPase, enzymes (including glycogen-synthase-kinase-3) and transcription factors (including FOXO3a, ss-catenin, NF-kappaB). A gain-of-function SGK1 gene variant, carried by approximately 3 - 5% of Caucasians and approximately 10% of Africans, is associated with increased blood pressure, obesity and type 2 diabetes. In vitro and in vivo experiments suggested a critical role of SGK1 in renal fluid retention and hypertension, glucose-induced obesity, coagulation and increased matrix protein formation.
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PMID:Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448. 2002 Dec 89

The presence of resistant pathogens in the lower airways of patients with cystic fibrosis (CF) is not an absolute contraindication for lung transplantation. We describe a case in which a patient with CF died as a result of an anastomotic dehiscence, ischemia, and infection with linezolid-resistant methicillin-resistant Staphylococcus aureus. We review infection issues during the post-lung-transplant period and related anastomotic dehiscence in CF.
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PMID:Airway dehiscence after lung transplantation in a patient with cystic fibrosis. 2112 82


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