Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular factors that regulate nitric oxide (NO) synthesis represent important targets in tumor progression. Overexpression of dimethylarginine dimethylaminohydrolase (DDAH), which metabolizes the endogenous inhibitors of NO synthesis asymmetric dimethylarginine and N-monomethyl-L-arginine, results in C6 gliomas with enhanced growth rate compared with wild type. To investigate the effects of DDAH on tumor vascular morphogenesis in vivo, we have measured the transverse relaxation rates R(2)* and R(2) in clone D27 gliomas overexpressing DDAH and C6 wild-type gliomas using intrinsic susceptibility magnetic resonance imaging (MRI), sensitive to changes in endogenous [deoxyhemoglobin], and susceptibility contrast-enhanced MRI using the intravascular blood pool contrast agent NC100150, and we compared the results with fluorescence microscopy of the tumor uptake of the perfusion marker Hoechst 33342. The baseline R(2)* was significantly faster in the D27 tumors, consistent with a greater vascular development (P < 0.02, ANOVA). There was no significant difference between the response of the two tumor types to hypercapnia (5% CO(2)/95% air), used as a probe for vascular maturation, or hyperoxia (5% CO(2)/95% O(2)), used as a probe for vascular function. NC100150 increased the R(2)* and R(2) rates of both tumor types and demonstrated a significantly larger blood volume in the D27 tumors (P < 0.02, ANOVA). This correlated with a significantly greater uptake of Hoechst 33342 in the D27 tumors compared with C6 wild-type tumors (P < 0.02, ANOVA). Despite the increased tumor blood volume, the Delta R(2)*/Delta R(2) ratio, an index of microvessel size, showed that the capillaries in the two tumor types were of a similar caliber. The data highlight the potential of susceptibility MRI-derived quantitative end points to noninvasively assess tumor angiogenesis, and in this regard, the use of intravascular blood pool contrast agents such as NC100150 appears very promising. Overexpression of DDAH results in increased neovascularization of C6 gliomas in vivo. The lack of significant difference in hypercapnic/hyperoxic response between the C6 and D27 tumors and the similar vessel caliber are also consistent with a role for DDAH in the initial stages of vasculogenesis.
Cancer Res 2003 Aug 15
PMID:Effects of overexpression of dimethylarginine dimethylaminohydrolase on tumor angiogenesis assessed by susceptibility magnetic resonance imaging. 1294 21

Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.
Int J Cancer 2005 Nov 01
PMID:Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis. 1588 Apr 97

Fourteen adult patients with haematological malignancies (eight non-Hodgkin's lymphoma, one multiple myeloma, one chronic lymphocytic leukaemia, two acute lymphoblastic leukaemia and two acute myeloid leukaemia) developed acute interstitial pneumonitis (IP) during the course of chemotherapy. All patients manifested high fever over 38 degrees C, bilateral diffuse pulmonary interstitial infiltrates in the chest radiograph and severe hypoxia without hypercapnia in the arterial blood gas analysis. Pathogenic microorganisms were not detected in repeated examinations in any patient. Chemotherapy given included various anti-neoplastic drugs. Five patients had received granulocyte colony-stimulating factor (G-CSF) for chemotherapy-induced leucopenia. The onset was associated with an increase of leucocytes in 10 patients. All patients were treated with high dose steroid hormone and broad spectrum antibiotics with or without anti-fungal agents, and three required mechanical ventilation. Eleven patients quickly recovered from these situations, whereas three died. Autopsies were done in two patients and disclosed pneumocystis carinii (PC) pneumonitis in one and non-specific pulmonary congestive oedema and fibrosis in the other. In conclusion, IP of unknown cause could develop in patients with various haematological malignancies especially at the recovery phase of chemotherapy-induced leucopenia irrespective of the previous G-CSF administration. High dose steroid hormone should be used as therapy for such patients as soon as possible after exclusion of an infective aetiology.
Eur J Cancer Care (Engl) 2005 Sep
PMID:Acute interstitial pneumonitis during chemotherapy for haematological malignancy. 1609 18

Past literature has shown that respiratory failure following hematopoietic stem cell transplant is associated with a universally poor outcome with mortality rates approaching 100%. More recent studies have suggested that patient survival is improving. We report our experience with the patients from our institution, a large children's hospital, who were admitted to the intensive care unit (ICU). Medical records of 183 patients, who received a bone marrow transplant between 1992 and early 2004, who were <20 yr of age, were retrospectively reviewed. Various factors that might influence mortality were examined. Over the course of the study, the ICU survival increased from 18% during the period 1992-1999 to 59% between 2000 and early 2004. In the latter period, 54% of the patients discharged from the ICU were alive at 100 days post-transplant. Factors that were significant predictors of poor outcome were malignancy as the reason for transplant, dialysis during the ICU stay, or extreme respiratory failure with a ratio of arterial oxygen tension (PaO2)/inspired oxygen concentration (FiO2) <300. Analysis of patients who required a high positive end-expiratory pressure or were ventilated with permissive hypercapnia showed that they also had a higher mortality. The impact on survival of factors such as age at time of transplant, graft-vs.-host disease, pneumonia, bacteremia, sepsis, post-transplant days, Pediatric Risk of Mortality III score, engraftment status, or veno-occlusive disease did not reach statistical significance in this cohort. Survival has improved for children who require intensive care following a bone marrow transplant, even for those who require mechanical ventilation. Patients with extreme respiratory failure and those requiring dialysis continue to have poor outcome. Because of an overall improvement in survival, children whose condition following transplant requires intensive care should be treated aggressively.
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PMID:Changing outcomes for children requiring intensive care following hematopoietic stem cell transplantation. 1667 52

Ischemia has elicited a great deal of interest among the scientific community due to its role in life-threatening pathologies such as cancer, stroke, acute renal failure, and myocardial infarction. Oxygen deprivation (hypoxia) associated with ischemia has recently become a subject of intense scrutiny. New investigators may find it challenging to induce hypoxic injury in vitro. Researchers may not always be aware of the experimental barriers that contribute to this phenomenon. Furthermore, ischemia is associated with other major insults, such as excess carbon dioxide (hypercapnia), nutrient deprivation, and accumulation of cellular wastes. Ideally, these conditions should also be incorporated into in vitro models. Therefore, the motivation behind this review is to: i. delineate major in vivo ischemic insults; ii. identify and explain critical in vitro parameters that need to be considered when simulating ischemic pathologies; iii. provide recommendations to improve experiments; and as a result, iv. enhance the validity of in vitro results for understanding clinical ischemic pathologies. Undoubtedly, it is not possible to completely replicate the in vivo environment in an ex vivo model system. In fact, the primary goal of many in vitro studies is to elucidate the role of specific stimuli during in vivo pathological events. This review will present methodologies that may be implemented to improve the applicability of in vitro models for understanding the complex pathological mechanisms of ischemia. Finally, although these topics will be discussed within the context of renal ischemia, many are pertinent for cellular models of other organ systems and pathologies.
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PMID:Experimental strategies to improve in vitro models of renal ischemia. 1749 Jun 40

KNI-472 is the first anesthetic system for mice and rats to incorporate a ventilator. It consists of a newly developed syringe pump-type vaporizer and gas monitor that can deliver accurate concentrations of anesthetic gas at an extremely low airflow. In this study, we compared the hemodynamic effects of isoflurane anesthesia using KNI-472 and intraperitoneal pentobarbital anesthesia. In the isoflurane anesthetic group, Institute of Cancer Research (ICR) mice were anesthetized with 5% isoflurane, followed by endotracheal intubation. Subsequently, they were ventilated mechanically, and anesthesia was maintained with 2% isoflurane for a 60-min period using KNI-472. In the pentobarbital anesthetic group, the ICR mice were anesthetized by an intraperitoneal injection of sodium pentobarbital (70 mg/kg). In isoflurane anesthesia, the heart rate (HR) and mean blood pressure (MBP) were stable. In contrast, in pentobarbital anesthesia, MBP decreased in the first stage after the initiation of anesthesia, after which it gradually increased. The intra-group variability in the estimated skin blood flow (SBF) was higher in the pentobarbital anesthesia than that in the isoflurane anesthesia. The PaO(2) and PaCO(2) values at 15 min after the initiation of pentobarbital anesthesia revealed hypoxia and hypercapnia compared with isoflurane anesthesia. In this study, isoflurane anesthesia using KNI-472, unlike pentobarbital anesthesia, did not induce changes in MBP, SBF, or blood gases. The changes induced by pentobarbital anesthesia were attributed to a change in the depth of anesthesia with time. These results indicate that inhalation anesthesia using KNI-472 is suitable in research on the hemodynamic state in mice.
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PMID:Comparison of newly developed inhalation anesthesia system and intraperitoneal anesthesia on the hemodynamic state in mice. 1782 27

Platelet-derived growth factors (PDGF) play a major role in pericyte recruitment in tumor capillaries. Pericytes are required for proper vessel development, and contribute to tumor angiogenesis by promoting stabilization and maturation of newly formed vessels. To investigate the effects of pericyte coverage on tumor vessel morphology and function in vivo, tumors derived from B16 melanoma cells transfected with either control plasmid (B16/ctr) or plasmid encoding full-length PDGF-BB (B16/PDGF), the latter previously shown to have enhanced blood vessel pericyte coverage and an increased tumor growth rate, were assessed using histopathological methods, Hoechst 33342-based perfusion analyses, and two noninvasive susceptibility magnetic resonance imaging (MRI) methods. Susceptibility-contrast MRI, incorporating the use of ultrasmall superparamagnetic iron oxide particles, revealed a significant (p < 0.05) reduction in vessel size index (R(v)) of B16/PDGF tumors, and which was validated histologically by the presence of significantly smaller (p < 0.001), more punctate blood vessels identified by fluorescence microscopy of the perfusion marker Hoechst 33342. Intrinsic-susceptibility MRI was used to measure the transverse MRI relaxation rate R(2)*, sensitive to changes in endogenous paramagnetic [deoxyhaemoglobin], and used to probe for vascular maturation and function. Hypercapnia (5% CO(2)/95% air) induced a negligible Delta R(2)* response in the B16/ctr and B16/PDGF tumors. In contrast, hyperoxia (5% CO(2)/95% O(2)) induced a significantly greater R(2)* reduction in the B16/PDGF tumors (p < 0.02). Together the susceptibility MRI-derived biomarkers reveal novel pericyte-dependent changes in the morphology and function of the perfused tumor vasculature in vivo.
Int J Cancer 2008 Apr 01
PMID:The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI. 1803 83

A 51-year-old man presented with back pain in 1997. He had a 30-year-history of occupational asbestos exposure. His chest CT showed bilateral pleural thickening and pleural effusion. The pleural effusion of the right thorax exhibited both elevated level of adenosine deaminase and increased numbers of lymphocytes. Antituberculous chemotherapy had no effect on the exudates. Progressive bilateral pleural thickening were found on chest CT, and pulmonary function tests showed severe restrictive ventilatory impairments since 1998. Thoracoscopic pleural biopsy was conducted in 2001 to exclude pleural malignant mesothelioma. No malignancy was found in pleural samples. After 3-year observation and excluding other causes, he was given a diagnosis of benign asbestos pleurisy. In 2005, fibrotic changes were found in both lower lung fields in chest CT. He suffered from respiratory failure with carbon dioxide retention, and died in 2006. The autopsy disclosed asbestos-related lung diseases. We suspected that diffuse pleural thickening could be a major cause of fatal respiratory impairment in this case.
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PMID:[Autopsy case of diffuse pleural thickening presenting respiratory impairment and benign asbestos pleurisy]. 1851 12

Red blood cells from patients with sickle cell disease will sickle under conditions of hypoxemia and acidosis which is a similar milieu found in malignant tumors. While control of tumor angiogenesis has long been a goal of cancer therapy, selective occlusion of tumor blood supply may be achieved by transfusion of sickle cells into patients who suffer metastatic cancer. Although this potential therapy has not been previously reported in the medical literature, the concept may have been elusive to medical mainstream thinking because it requires transfusion of diseased cells. For this therapy to be effective, other environmental factors may need to be manipulated such inducing mild hypoxemia or hypercarbia (respiratory acidosis) to induce red cell sickling. Preliminary evidence supportive of this therapeutic approach to cancer treatment is provided by case evidence that sickle cell occlusion of a malignant brain tumor (glioma) produced tumor necrosis. Also sickle cells have been successfully transfused into primates. Furthermore, donor blood is crossmatched and transfused into patients suffering from sickle cell disease regularly in clinics and this procedure is associated with acceptable morbidity. Most importantly, animal models of sickle cell disease and cancer currently exist, and this theory could be tried with available technologies including ultrasound detection of vaso-occlusion. While the proposed therapy may not cure metastatic cancer, this treatment could prove useful for decreasing the size and perhaps the pain from metastatic tumor burden. Therefore, it is hypothesized that ABO Rh compatible crossmatched sickle cells transfused into patients who suffer metastatic cancer under controlled conditions of blood oxygenation and pH will selectively produce vaso-occlusive infarcts in malignant tumors and be a useful therapy. The author hopes for further investigations.
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PMID:Transfusion of sickle cells may be a therapeutic option for patients suffering metastatic disease. 2044 56

Laparoscopic colectomy has been reported as an alternative for treatment of colorectal cancer. However, its long-term efficacy and safety remain obscure. The purpose here was to review our experience with laparoscopic colectomy in 899 patients between June 2001 and December 2008. Of them, 43 patients were converted to open surgery and 846 accepted laparoscopic colorectomy successfully. Among these 846 patients, 790 patients underwent radical resection and 56 patients underwent palliative resection. Only 1 patient died from perioperative pulmonary infection; thus the mortality was 0.12% (1/846). The morbidity of perioperative complications was 18.20% (154/846): intraoperative complication rate was 4.49% (38/846) and the most common intraoperative complication was subcutaneous emphysema and hypercapnia (1.65%, 14/846); postoperative complication rate was 13.71% (116/846) and the most common postoperative complication was ileus (4.37%, 37/846). The overall followed-up rate was 86.41% (731/846, 680 for radical operations and 51 palliative operations). Postoperative deaths happened to 139 patients, including 112 after radical operation and 27 after palliative resection. Of these 112 patients, 97 deaths were cancer-related (14.26%, 97/680) and 15 deaths were non-cancer-related. There were 10 patients encountered local recurrence (1.47%, 10/680) and 105 for metastasis (15.44%, 105/680) after radical operation. Forty-two patients are still alive with tumor. Overall survival rate was 80.98% (592/731), 3-year disease-free survival (DFS) rate after radical operation was 78.0%, and 3-year DFS rate after radical operation for stage I, stage II, and stage III was 89.0%, 85.0%, and 65.0%, respectively. In conclusion, laparoscopic colorectal resection is a feasible and safe technology for colorectal cancer.
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PMID:Laparoscopic colorectomy for colorectal cancer: retrospective analysis of 889 patients in a single center. 2272 50


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