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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was conducted to examine the feasibility of cisplatin-based chemotherapy in elderly patients (> or = 75 years old) with advanced non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Thirty-four patients were enrolled between September 1993 and December 1994. Patients with normal organ function and good performance status (PS) received cisplatin-based chemotherapy (cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 2 and 8 for NSCLC, or cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 2 to 4 for SCLC). Ten patients (29%) were eligible for this study, 7 with NSCLC and 3 with SCLC. Reasons for exclusion were ischemic heart disease in 14, poor PS (> or = 2) in 11, reduced creatinine clearance (Cer) in 10, abnormal electrocardiogram without ischemia in 9 and noncompliance with the protocol in 2 patients. Eight patients had two or more reasons. Nine of the 10 eligible patients were able to tolerate two or more courses of chemotherapy. All 3 patients with SCLC responded (1 complete response and 2 partial response), but only 1 of the patients with NSCLC achieved partial response. Toxicity was evaluated according to Japan Clinical Oncology Group criteria. All but one patient experienced grade 4 neutropenia, and 6 patients had infectious episodes requiring antibiotics. Grade 3 anemia and thrombocytopenia were observed in 1 and 2 patients, respectively. Non-hematological toxicities were mild. Only 10 of 34 patients (29%) satisfied our eligibility criteria and they experienced severe myelotoxicity. We conclude that chemotherapy should be given carefully to elderly patients even if they appear to have normal organ function.
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PMID:Prospective evaluation of the feasibility of cisplatin-based chemotherapy for elderly lung cancer patients with normal organ functions. 863 10

The involvement of neutrophils in the pathogenesis of cerebral ischemic injury in two rat models of focal ischemia was investigated. In Experiment I, a model of focal ischemia with partial reperfusion was used. Although significant and discrete ischemic damage within the neocortex was nearly maximal at 12 h postocclusion, no elevation in neutrophils was seen at this time point. Even after 21 h postocclusion, only a subtle increase in neutrophils within the ischemic tissue was observed. To further investigate the possible role of neutrophils in cerebral ischemia, the effect of cyclophosphamide-induced neutropenia was investigated (Experiment II). While a marked reduction (>98%) in systemic neutrophils was achieved in advance of and during the ischemic challenge, no reduction in the volume of ischemic damage was observed. In Experiment III, variations in the rat model of focal ischemia were made to produce a larger area of ischemic damage, as well as to permit complete reperfusion of blood to the affected cortex. While more neutrophils were seen in this variation of the model, very few were observed (< 1 per field) prior to the time that maximal ischemic damage had already occurred. Together, these experiments revealed that substantial brain necrosis occurred prior to the appearance of neutrophils, under conditions of partial, as well as complete, reperfusion. Moreover, at the time points when elevations in neutrophils were observed, no further increase in volume of ischemic damage was noted. Finally, pharmacologic removal of neutrophils prior to ischemia did not alter the size of the ischemic region. These data therefore fail to support the hypothesis that neutrophils play a general and essential role in infarct formation following focal brain ischemia and argue that further studies are required to more clearly elucidate the conditions under which neutrophils might participate in ischemic pathogenesis.
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PMID:Lack of evidence for neutrophil participation during infarct formation following focal cerebral ischemia in the rat. 865 22

Reperfusion injury, precipitated by lack of oxygen, is likely to play a major role in many clinical conditions, including shock, coronary artery occlusion disease, and solid organ transplantation. Certain tissues, such as the intestinal mucosa, may be especially susceptible because of the specific microvascular anatomy. Structural changes include not only swelling of the organelles but also the entire cell due to the entry of water and electrolytes. Lysosomal ruptures precede cell death. Other key substances which either participate in or are part of oxygen free radical formation in tissue injury are calcium ions, leukocytes, and bacteria. Leukocyte adhesion has been implicated as a critical step in vascular endothelium injury, leading to increased microvascular permeability and thrombosis. Induction of neutropenia or the administration of antileukocyte adhesion monoclonal antibodies, preventing typical injuries, implies a central role of the white blood cells in reperfusion injury. Specifically, oxygen free radical formation in the intestines may trigger or cause injury in other distant organs, e.g., the heart and lungs, and affect overall vascular function. So-called "bacterial translocation" from the intestines to the lymphatic vessels and the bloodstream is a more recently discovered phenomenon whose role is largely unknown. Ischemic preconditioning is still another concept, mainly tested in the canine heart, that has potential clinical applications. Reperfusion of ischemic tissue occurs with solid organ transplantation, often after considerable cold ischemia time. Protective mechanisms include oxygen free radical scavengers, i.e., allopurinol and superoxide dismutase. Other measures proven to be effective during the implantation are blood volume expansion with colloid solutions and/or electrolyte solutions, and the administration of a calcium antagonist. The mechanisms of these measures are likely related to improved renal microcirculation and relief of vasospasm.
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PMID:Reperfusion injury. 877 98

Using a gerbil model of severe, temporary focal ischemia (3 h unilateral carotid occlusion), preliminary experiments identified an involvement of neutrophils in the reperfusion injury to the ischemic hemisphere. The present experiments were designed to (1) quantitate the temporal accumulation of neutrophils in the gerbil model, (2) determine if cyclophosphamide-induced neutropenia provided cytoprotection to the ischemic hemisphere, and (3) attempt to correlate the cytoprotective efficacy of tirilazad mesylate with possible effects on postischemic neutrophil accumulation. Following 3 h of unilateral carotid occlusion, animals were collected at increasing times of reperfusion and the CA1 region of the hippocampus and the lateral cortex were assessed for postischemic neuronal damage using a semiquantitative index (N.D.I.) of 0 (no damage) to 4 (>75% neuronal loss). The extent of neutrophil accumulation was determined by counting intensely cytochrome oxidase-positive cells. Minimal neuronal death was evident after 2 h of reperfusion, mean N.D.I. = 0.36. However, between 2 and 4 h of reperfusion, neuronal death did not increase. By 6 h of reperfusion, the neuronal death began to proceed at an accelerated rate, N.D.I. = 0.78. By 12 h, the N.D.I. reached 3.20. The accelerated neuronal death coincided with parenchymal invasion of neutrophils. Cyclophosphamide administration delayed neuronal death in the hippocampus, but exhibited a more sustained protective effect in the lateral cortex. Administration of tirilazad mesylate also resulted in a significant reduction in neutrophil accumulation and significant neuronal protection in both brain areas. Thus, in this gerbil model of transient, but prolonged focal cerebral ischemia, neutrophils appear to play an active role in the reperfusion injury to brain tissue. Our experiments confirm the previously demonstrated neuroprotective efficacy of tirilazad mesylate in this model and provide evidence for a similar protective effect of cyclophosphamide. Although other effects of this antioxidant are also thought to contribute to the overall efficacy, the data are consistent with the hypothesis that one mechanism by which tirilazad acts involves limiting the ability of neutrophils to participate in the reperfusion phase of ischemic cerebral injury.
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PMID:Cyclophosphamide is neuroprotective in a gerbil model of transient severe focal cerebral ischemia: correlation with effects of tirilazad mesylate (U-74006F). 909 81

Neutrophils contribute to ischemic brain injury in adult animals. The role of neutrophils in perinatal hypoxic-ischemic (HI) brain injury is unknown. Allopurinol reduces neutrophil accumulation after tissue ischemia and is protective against HI brain injury. This study was designed to investigate how neutrophils contribute to perinatal hypoxic ischemic brain injury and how neutropenia compared with allopurinol in its neuroprotective effects. A HI insult was produced in the right cerebral hemisphere of 7-d-old rats by right common carotid artery ligation and systemic hypoxia. Half the rats were rendered neutropenic with an anti-neutrophil serum (ANS). At 15 min of recovery from hypoxia, half the neutropenic and nonneutropenic rats received allopurinol (135 mg/kg, s.c.). The protective effect of the four treatment combinations was determined on brain swelling at 42 h of recovery. Neutropenia reduced brain swelling by about 70%, p < 0.01. Allopurinol alone produced similar protection so that the relatively small number of animals studied did not permit assessment of an additive effect. Neutrophil accumulation in cerebral hemispheres was measured by myeloperoxidase (MPO) activity assay and by neutrophil counts in 6-microm sections stained by MPO and ANS immunostaining. MPO activity peaked between 4 and 8 h of recovery in both hemispheres. Hemispheric neutrophil counts peaked at the end of the HI insult and again at 18 h of recovery. Neutrophils were stained within blood vessels and did not infiltrate the injured brain before infarction had occurred. We conclude that neutrophils contribute to HI brain injury in the neonate and that neutrophil depletion before the insult is neuroprotective.
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PMID:The role of neutrophils in the production of hypoxic-ischemic brain injury in the neonatal rat. 912 80

It has been reported that activated neutrophils are involved in the development of cerebral damage induced by ischemia. Activated neutrophils release a lot of mediators including toxic oxygen metabolites, elastase and cytokines which damage brain tissue. Therefore, we investigated roles of neutrophil elastase in the development of cerebral damage using an elastase inhibitor, ONO-5046. The rat middle cerebral artery (MCA) was occluded by a thrombus induced by photochemical reaction between green light and the photosensitizer dye, Rose Bengal. Photochemical reaction causes endothelial injury followed by formation of a platelet and fibrin-rich thrombus at the site of the irradiation. Photochemical reaction is routinely used in our laboratory to produce arterial occlusion in experimental animals. Twenty-four hours after the MCA occlusion, the size of cerebral damage was measured by histochemical technique. Water content in the brain was measured and neuronal deficits were examined 24 h after the MCA occlusion. ONO-5046 was administered at various doses as continuous infusion for 24 h, starting just after the MCA occlusion or from 3 h after. ONO-5046 at doses of 10 and 30 mg/kg/h significantly (p<0.05 and p<0.01, respectively) reduced the size of cerebral damage and water content (p<0.05, p<0.01, respectively) in different eight rats. Further, ONO-5046 at a dose of 30 mg/kg/h significantly (p=0.01) improved neuronal deficits. ONO-5046 which was administered starting from 3 h after the MCA occlusion, also reduced the size of cerebral damage. Neutropenia by anti-neutrophil antibody injection significantly (p<0. 01) reduced the size of cerebral damage. Elastase released from activated neutrophils may play a key role in the development of cerebral damage.
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PMID:Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion. 1070 May 96

The term intestinal necrosis is nothing but a clinical and pathological concept and always includes intestinal ischemia, whether or not occlusive. In a broad sense, necrotizing enterocolitis involves intestinal ischemia associated to an infectious entity. The precipitating factor for necrosis is very often difficult to identify. Necrotizing enterocolitis occurs in 90% of cases in premature neonates and is less frequent amongst other neonates, being rare in older children and adults. The authors present two clinical cases: one 7 year-old with a history of chronic neutropenia and an eleven-year old with severe cognitive impairment, dysmorphic features and behavioural disturbances. They were both admitted to hospital due to an acute abdominal condition and shock. The necrosis implied the resection of a jejunal segment in one of the cases, and a subtotal colonic resection in the other. Despite the surgery and medical support therapy, they both died due to multiple system organ failure--3 hours and fourteen days after surgery, respectively. In the second case, death occurred subsequent to a second surgery for resection of a segment of necrotic ileum. Necropsy showed an extensive necrosis of the remaining intestine in both cases. These two cases evolved as necrotizing enterocolitis of the child. In one of the cases it was possible to establish the exclusion diagnosis of neutropenic enterocolitis. The etiopathogenic mechanisms are reviewed, including thrombotic, obstructive (both extrinsic and endoluminal), inflammatory, non-occlusive ischemic and infectious. The authors stress the general therapeutic measures, the relevance of early surgical intervention and the use of subsidiary diagnostic/therapeutic technologies, such as serum and urine title of intestinal fatty acid binding protein or selective arteriography.
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PMID:[Intestinal necrosis in children]. 1123 98

A rat model of reversible occlusion of the middle cerebral artery was developed to assess the role of neutrophils and prophylactic hyperbaric oxygen (HBO2) on cerebral injury. Blood flow to the ipsilateral caudate putamen nucleus was reduced by approximately 50% during 2 h of arterial occlusion, but unaffected on the contralateral side. Neutrophil accumulation in brain was documented as myeloperoxidase concentration, which was elevated in both ipsilateral and contralateral cerebral hemispheres at 1 and 46 h after occlusion/reperfusion. HBO2 administered before ischemia at 2.8 atm abs for 45 min, as well as antibody-induced neutropenia, reduced neutrophil accumulation, functional neurologic deficits, and cerebral infarct volume. These data demonstrate that one mechanism for benefit of HBO2 is related to its ability to ameliorate post-ischemic injury by inhibiting neutrophil sequestration. This mechanism should be taken into consideration when choosing partial pressures of oxygen for investigational clinical protocols.
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PMID:Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. 1141 58

Oxygen free radicals (OFR) and neutrophils are potent sources of reperfusion injury. We compared the effect of EPC-K1, a new OFR scavenger, and neutrophil depletion on the reperfusion injury in skeletal muscle, using an ischemic revascularized hindlimb model in rats. Warm ischemia, produced by vascular pedicle clamping, was sustained for 4 h. After 24 h of reperfusion, muscle function and damage were evaluated in 4 groups: a sham operation group, a control study group, a group treated by EPC-K1 (EPC group), and a group that received nitrogen mustard to induce neutropenia (NM group). Both the EPC and NM groups had limited muscle damage compared to the control group. The EPC group preserved muscle function significantly better than the control group and the mean isometric tetanic tension in the EPC group appeared to be higher than that in the NM group. Furthermore, levels of lipid peroxides in muscle and serum, and muscle edema in the EPC group, were significantly lower than in the NM group. Histological examinations supported these results. These findings suggest that limiting OFR generation by EPC-K1 in the early phase of reoxygenation is more potent than depletion of neutrophils in reducing reperfusion injury.
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PMID:Effects of a hydroxyl radical scavenger, EPC-K1, and neutrophil depletion on reperfusion injury in rat skeletal muscle. 1158 Jan 30

Data accumulated over the last 10 years have led to the popular hypothesis that neutrophils and other inflammatory cells play a prominent role in the neuropathology of cerebral ischemia. This hypothesis was derived from a large number of studies involving three general observations: (1) leukocytes, particularly neutrophils, are present in ischemic tissue at the approximate time that substantial neuronal death occurs; (2) neutropenia is sometimes associated with reduced ischemic damage; and (3) treatments that prevent leukocyte vascular adhesion and extravasation into the brain parenchyma can be neuroprotective. This review reexamines the literature to ascertain its support for a pathogenic role for neutrophils in ischemia-induced neuronal loss. To accomplish this goal, we employed several logical theorems of "cause-effect" relationships, as they pertain to leukocytes and ischemic brain damage. Since the majority of studies focused on neutrophils as the most likely pathogenic inflammatory cell, this review necessarily does so here. We reasoned that if neutrophils play an important pathogenic (i.e., cause-effect) role in the neuronal damage that follows a stroke, then one should expect to find clear evidence that: (1) neutrophils invade the ischemic area prior to terminal stage infarction, (2) greater numbers of early appearing neutrophils are accompanied by evidence of greater neuronal loss, and (3) dose-related inhibition of neutrophil trafficking or activity produces a corresponding decrease in the degree of brain damage following ischemia. This review of the literature reveals that the existing evidence does not readily support any of these predictions and that, therefore, it consistently falls short of establishing a clear cause-effect relationship between leukocyte recruitment and the pathogenesis of ischemia. While the available evidence does not necessarily rule out a potential pathogenic role of neutrophils and other leukocytes, it nevertheless does expose serious weaknesses in the existing studies intended to support that hypothesis. For this reason we also offer suggestions for additional experiments and the inclusion of control groups that, in the future, might provide more effective or conclusive tests of the hypothesis.
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PMID:The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? 1177 49


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