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)

Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was speculated that pentostatin would be lymphocytotoxic, and this proved to be the case, promoting its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA---e.g., acute lymphocytic leukemia (ALL), particularly its T cell variety. Although pentostatin proved to be active in ALL, large doses were required and toxic effects outweighted therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T cell lymphomas, adult T cell lymphoma-leukemia, and low-grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppression, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppresive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia.
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PMID:Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role In Cancer Chemotherapy, and Future Prospects. 1184 52

Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities.
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PMID:[Acute liver failure due to T cell lymphoma without hepatic infiltration]. 1262 21

Renal transplant is the treatment of choice for the patient with end stage renal disease. Spain is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.
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PMID:[Present and future of kidney transplantation]. 1264 71

In intravascular lymphoma (IVL) tumor cells are initially restricted to vascular lumina. Neurological syndromes predominate and are caused by ischemia as well as tumor infiltration into the nervous system. Ante mortem diagnosis is challenging and frequently impossible. Chemotherapy is effective if started prior to ischemic damage. Over a three year period, we have diagnosed IVL in seven patients. Tissue diagnosis could be accomplished in only three cases. Forthose in whom tissue diagnosis failed we based our diagnosis on clinical presentation, typical magnetic resonance imaging findings, spinal fluid cytopathology, and molecular analyses. Six patients were treated with methotrexate chemotherapy alone or in combination with CHOP. Three patients are in complete remission 9-20 months after initial diagnosis. Another patient achieved a partial response. Two patients died due to progressive disease shortly after initiation of treatment. Grade III toxicity was observed in only 4 of 61 cycles. Based on a small retrospective series of patients, we conclude that methotrexate is a well tolerated and effective agent for the treatment of IVL.
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PMID:A new approach to the diagnosis and treatment of intravascular lymphoma. 1267 17

Malignant lymphomas cause various neurological complications by several ways. They include 1) infiltration and compression due to lymphoma itself, 2) ischemia due to intravascular proliferation of lymphoma cells, 3) paraneoplastic syndrome, 4) immunodeficiency due to lymphomas, 5) organ dysfunction due to lymphomatous infiltration, and 6) complication related to therapies against lymphomas. We presented 4 patients with neurological complications caused by B cell lymphomas as follows. Our first patient was a 67-year-old woman with primary intracranial lymphoma whose onset simulated that of a cerebral infarct. The second patient was a 52-year-old man with lymphoma, who developed myelopathy caused by an intradural extramedullary spinal cord tumor. He received chemotherapy and radiation therapy, followed by complete remission. The third was a 80-year-old man with left cavernous sinus syndrome, which did not respond to therapies against lymphoma. The fourth was a 55-year-old man who presented with numb chin syndrome on both sides, followed by multifocal lymphomatous involvement of the cranial nerves, spinal roots and leptomeninges. Malignant lymphomas may affect any regions of the central and peripheral nervous systems by various ways. Early diagnosis and treatment are essential for the better outcome of neurological complications due to lymphomas.
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PMID:[Clinical aspects and pathogenesis of neurological complications due to malignant lymphomas]. 1278 81

A 54-year-old man with a past history of gastric malignant lymphoma treated by the total gastrectomy and the chemotherapy, developed bilateral sudden deafness one year later. Two years after the gastrectomy he became abruptly paraplegic with sensory impairments of the lower extremities and neurogenic bladder. Serum LDH and soluble IL-2 receptor were high in titers (552 U/l and 1,090 U/l, normal range 145-519). Although the imaging studies of the spinal cord were negative, the myelopathic symptoms resolved dramatically after a course of pulse dose methylprednisolone therapy. However, he soon developed an abnormal behavior and mental deterioration in 3 weeks. The MRIs of the brain revealed abnormal signals compatible with multiple cerebral infarctions. As intravascular malignant lymphomatosis (IML) was suspected because of the laboratory and MRI findings, biopsies of the skin, the bone marrow, the muscle and the lymph node were carried out, without evidence of lymphoma. The brain biopsy ultimately confirmed the presence of IML. The patient remarkably responded to biweekly CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in terms of regaining the mental alertness and improved hearing. However, the CHOP therapy was prematurely interrupted prior to completion because of infective arthritis. The relapse soon ensued, and he died 6 months after admission. This case was of interest because a solid gastric lymphoma appears to have transformed into the form of intravascular lymphomatosis without mass formations or leukemic changes. Although the neurological symptoms in association with IML are thought to be the results of ischemic events, this case illustrates a remarkable reversibility of the symptoms. This implies that the cerebral symptoms are not necessarily the results of typical ischemic infarction, but due to relative ischemia because of chiefly capillary-venous occlusion by lymphoma cells. The majority of the symptoms is thus attributable to the functional impairment. Therefore, the therapeutic intervention may dramatically improve the symptoms due to IML.
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PMID:[Dramatic but temporary improvements in a case of CNS intravascular malignant lymphomatosis]. 1282 May 43

A 56-year-old man presented with fever, disorientation, and testicular pain. He was receiving azathioprine immunosuppression for autoimmune hepatitis. Orchiectomy identified occlusion of spermatic cord vessels by intravascular large B-cell lymphoma (IVLBL) and ischemic changes in the testis. Tumor cells were positive for CD 10, CD 20, CD 30, and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and early region RNA (EBER). He was treated with the cessation of azathioprine, chemotherapy, anti-CD 20 immunotherapy, and radiotherapy. Twenty months after diagnosis, he is alive with no evidence of lymphoma or hepatitis. This is the first report of IVLBL presenting with testicular ischemia. It highlights the importance of prompt diagnosis and intervention to achieve durable response. That this lymphoma arose in the setting of immunosuppressive therapy introduces additional complexity relating to pathogenesis, clinical behavior, and treatment.
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PMID:Testicular ischemia due to intravascular large B-cell lymphoma: a novel presentation in an immunosuppressed individual. 1461 32

Irradiation of the heart begets different complications in which pericardial disease is the most common manifestation. Thoracic irradiation of lymphoma, Hodgkin's disease, lung and breast cancer could be complicated by adverse effects to every structure of the heart. Potential injury of mediastinal irradiation can include acute and late pericarditis, cardiomyopathy, valvular disease and conduction abnormalities. The pathophysiology of these various syndromes is probably similar, starting by prior microvascular injury that leads to subsequent myocardium ischemia, all of which cause late fibrous scars. Acute pericarditis is often asymptomatic and clear spontaneously. Late pericarditis affects approximately 5% of the patients when the irradiation dose exceeds 40 Gy. At this dose, the mortality rate is below than 1%. Cardiomyopathy is rare and often asymptomatic. A long time unrecognized, coronary artery disease, diagnosed in 5 to 10% of the patients, begets multifarious sequelae like myocardial infarction, valvular abnormalities and cardiac rhythm changes. This coronary artery disease is more likely to occur if the patient was young at the time of the irradiation (< or = 21 years) and/or if other cardiovascular risk factors are associated. Incidence and mortality rates of valvular defects are about 20 and 0.5%, respectively. Conduction dysfunctions can also be seen in 5% of the patients. Radiation-induced heart complications seem to be related to total dose (> 30 Gy), irradiated tissue volume and fraction size. Since cardiac complications appear months to years following incidental irradiation of the heart, appropriate screening and long-term cardiac follow-up of these patients is essential.
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PMID:[Radiation toxicity to the heart: physiopathology and clinical data]. 1589 21

Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.
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PMID:Gastrointestinal complications in renal transplant recipients. 1591 Feb 87

Brief exposure to isoflurane or repetitive, transient ischemia during early reperfusion after prolonged coronary artery occlusion protects against myocardial infarction by inhibiting the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP during delayed ischemic preconditioning occurred concomitant with enhanced expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2). We tested the hypothesis that Bcl-2 mediates myocardial protection by isoflurane or brief ischemic episodes during reperfusion in rabbits (n = 91) subjected to a 30-min left anterior descending coronary artery occlusion followed by 3 h reperfusion. Rabbits received 0.9% saline, isoflurane (0.5 or 1.0 minimum alveolar concentration, MAC) administered for 3 min before and 2 min after reperfusion, 3 cycles of postconditioning ischemia (10 or 20 s each) during early reperfusion, 0.5 MAC isoflurane plus 3 cycles of postconditioning ischemia (10 s), or the direct mPTP inhibitor cyclosporin A (CsA, 10 mg/kg) in the presence or absence of the selective Bcl-2 inhibitor HA14-1 (2 mg/kg, i.p.). Isoflurane (1.0, but not 0.5, MAC) and postconditioning ischemia (20 s but not 10 s) significantly (P < 0.05) reduced infarct size (mean +/- sd, 21% +/- 4%, 43% +/- 7%, 19% +/- 7%, and 39% +/- 11%, respectively, of left ventricular area at risk) as compared with control (44% +/- 4%). Isoflurane (0.5 MAC) plus 10 s postconditioning ischemia and CsA alone also exerted protection. HA14-1 alone did not affect infarct size nor block protection produced by CsA but abolished reductions in infarct size caused by 1.0 MAC isoflurane, 20 s postconditioning ischemia, and 0.5 MAC isoflurane plus 10 s postconditioning ischemia. The results suggest that Bcl-2 mediates isoflurane-induced and ischemic postconditioning by indirectly modulating mPTP activity in vivo.
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PMID:The influence of B-cell lymphoma 2 protein, an antiapoptotic regulator of mitochondrial permeability transition, on isoflurane-induced and ischemic postconditioning in rabbits. 1663 8


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