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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of rhesus macaques with nonlethal total-body x-irradiation (400 R) prolonged survival time from an average of 15 hours to 101 hours after intravenous (IV) inoculation of 50 microgram of staphylococcal enterotoxin B (SEB)/kg of body weight. Radiation exposure per se did not produce detectable cardiorenal changes; however, the longer survival after SEB challenge exposure in x-irradiated rhesus macaques was associated with improved cardiorenal functions if compared with that of nonirradiated macaques given the same dose of SEB. Total-body radiation exposure 4 days prior to IV SEB inoculation prevented typical SEB-induced decreases (where measured at 5 hours) in cardiac output, stroke volume, TcH2O, CPAH, Cosm, and urine flow, as well as increases in total peripheral and renal resistance. A theory concerning the significance of radiation-induced leukopenia on modification of SEB-induced cardiorenal functions is postulated.
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PMID:Effect of staphylococcal enterotoxin B on cardiorenal functions and survival in X-irradiated rhesus macaques. 9 79

Cardiac dysfunction after cardiopulmonary bypass (CPB) has been reported by various investigators. Oxygen free radicals have been shown to depress cardiac function and contractility. To evaluate the possible role of oxygen free radicals (OFR) in post-pump cardiac dysfunction, measurements of cardiac function, OFR producing activity of polymorphonuclear (PMN) leukocytes (PMN chemiluminescence) and malondialdehyde (MDA), a lipid peroxidation product, in blood were made at induction of anesthesia (T1), before cross clamping of the aorta (T2), after closure of the chest (T3), and 24 hours postoperatively (T4) in 21 patients undergoing aortocoronary bypass surgery. The total OFR-derived chemiluminescence at T1, T2, T3, and T4 was 1590 +/- 156, 3169 +/- 338, 1972 +/- 214, and 2614 +/- 366 mv.min.10(6) PMN-1, respectively. Superoxide dismutase (SOD)-inhibitable chemiluminescence at T1, T2, T3, and T4 was 1214 +/- 129, 2674 +/- 328, 1752 +/- 215, and 2139 +/- 292 mv.min.10(6) PMN-1, respectively. Superoxide anion at T1, T2, T3, and T4 was 0.99 +/- 0.14, 1.30 +/- 0.17, 1.07 +/- 0.14, and 1.19 +/- 0.12 nmol.10(6) PMN-1.30 min-1, respectively. Blood MDA at T1, T2, T3, and T4 was 0.17 +/- 0.02, 0.25 +/- 0.03, 0.20 +/- 0.03, and 0.23 +/- 0.02 nmol/ml, respectively. OFR-derived and SOD inhibitable chemiluminescence, superoxide anion, and blood MDA increased significantly during CPB and postoperatively. There were decreases in the blood pressure and stroke volume, and increases in the central venous pressure, capillary wedge pressure, and heart rate during CPB and postoperatively. Cardiac output remained unchanged during this procedure. There was leukopenia during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. 130 23

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58

By selectively infiltrating and destroying the internal elastica of a major cerebral artery, Aspergillus fungus (Af) induces disruption and incipient dilatation of the vascular wall with or without inflammation. This unique pathogenetic mechanism of forming "true" fungal mycotic aneurysms (FMAs) was clearly demonstrated in a middle-aged adult male who died of a pontine stroke. The latter was secondary to thrombosis in the basilar artery of which the internal elastica was infiltrated and replaced by Af hyphae. The patient had diabetes, liver cirrhosis with oesophageal varices, and received multiple blood transfusions. However, leukopenia was not present and immunosuppressive drugs were not used. This case prompted comparison of the natural history and pathogenesis of bacterial and fungal mycotic aneurysms in cerebral arterial branches. Selective destruction of the internal elastica with progressive dilation at a segment of vascular wall insinuates a potential pathogenetic process involved in the formation of saccular or berry aneurysm. Management and therapeutic approaches for FMA are discussed.
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PMID:A proposed pathogenetic process in the formation of Aspergillus mycotic aneurysm in the central nervous system. 821 10

Cytokines and eicosanoids are well documented important mediators of endotoxemia. Bicyclic imidazoles are a novel class of nonsteroidal anti-inflammatory compounds that display unique pharmacological profiles by reducing cytokine production and arachidonic acid metabolism. In this study, we evaluated the ability of the bicyclic imidazole, SK&F 86002, to attenuate endotoxin-induced cardiopulmonary dysfunction. Pigs were randomly assigned to one of four groups: LPS (n = 5), given .5 microgram/kg/h 055:B5 Escherichia coli lipopolysaccharide (LPS) intravenously (i.v.) for 6 h; saline (n = 5); SK&F 86002 (n = 3), given 50 mg/kg SK&F 86002 orally 30 min prior to anesthesia; and SK&F 86002 + LPS (n = 5). Administration of LPS resulted in cardiopulmonary dysfunction characterized by decreased stroke volume and arterial oxygen tension, and increased room air alveolar-arterial oxygen gradient, pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure. Additionally, LPS administration was associated with leukopenia and increased pulmonary myeloperoxidase activity. Pretreatment with SK&F 86002 attenuated LPS induced hypotension, hypoxemia and bronchoconstriction and blocked the pulmonary hypertension. SK&F 86002 blocked the LPS-induced increase in myeloperoxidase activity, indicating a reduction in pulmonary neutrophil infiltration, but had no effect on systemic leukopenia. Pretreatment with SK&F 86002 significantly attenuated LPS-induced increases in plasma thromboxane B2 and tumor necrosis factor-alpha. We hypothesize that ameliorating effects of SK&F 86002 in this endotoxin model of cardiopulmonary dysfunction are related to inhibition of cytokine and eicosanoid biosynthesis.
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PMID:SK&F 86002, a dual cytokine and eicosanoid inhibitor, attenuates endotoxin-induced cardiopulmonary dysfunction in the pig. 894 52

Twenty-two patients with hemoblastosis were examined in order to evaluate the possibility of using the criteria of the total system's inflammatory response syndrome (TSIRS) for the diagnosis of sepsis in hemoblastosis patients with leukopenia. The patients were examined before and after chemotherapy. Twelve patients with myelotoxic leukopenia developed TSIRS in response to a concomitant infection. No intensive care and resuscitation were needed in 9 of them; antibiotic therapy rapidly improved the clinical status. Three of these patients had to be transferred to intensive care wards. These patients differed from patients with TSIRS who needed no intensive care and from patients without TSIRS by higher fever (39.6 +/- 0.9, 39.1 +/- 0.4, and 36.5 +/- 0.7 degrees C, respectively), tachycardia (114.1 +/- 19.1, 105.3 +/- 12.8, and 84.0 +/- 10.0 stroke/min, respectively), thrombocytopenia (35.4 +/- 33.2.10(9), 55.1 +/- 34.5.10(9), and 89.2 +/- 95.1.10(9)/liter, respectively), prolongation of XIIa-dependent fibrinolysis (161.0 +/- 67.5. 64.7 +/- 57.0, and 46.2 +/- 45.8 min, respectively), decreased content of antithrombin III (79.6 +/- 8.1, 102.0 +/- 16.2, and 98.9 +/- 11.9%, respectively), and a more grave status according to the APACHEII score (20.4 +/- 5.2, 15 +/- 2.0, and 10.8 +/- 3.2, respectively). The APACHEII score and XIIa-dependent fibrinolysis were in direct correlation. We consider that the TSIRS/sepsis criteria are highly sensitive but not specific. They just permit singling out the group of patients part of whom may have sepsis.
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PMID:[Criteria of systemic inflammatory response syndrome are unacceptable in the diagnosis of sepsis in patients with leukopenia]. 1005 Mar 44

Cerebrovascular accident (CVA) is a major cause of morbidity and death in sickle cell anemia (SCA). Transfusion of packed erythrocytes is widely used to prevent this complication. However, chronic transfusion may lead to iron overload, alloimmunization, or infections. Cost and compliance may compromise transfusion therapy. A possible alternative, the prophylactic use of hydroxyurea (HU), has not been tried to determine whether it may prevent recurrent stroke. We used HU in five children with SCA who had suffered stroke, in three of them after a first episode and in the other two after a second CVA. Four had infarctive stroke and one a transient ischemic attack (TIA). Four patients took HU at a dose of 40 mg/kg/d, one patient at 30 mg/kg/d. None of the patients had recurrent stroke during 42-112 months of observation. None experienced pain crises. In all, HbF increased significantly and was maintained above 14.7% during treatment. The total Hb concentration increased 19.5 g/L (median) above the value before treatment. HU was well tolerated. None of the five children had leukopenia or thrombocytopenia during therapy. HU appears to prevent recurrence of stroke in SCA without risk of major toxicity.
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PMID:Hydroxyurea (HU) for prevention of recurrent stroke in sickle cell anemia (SCA). 1241 May 69

The presence of antiphospholipid (aPL) antibodies and antiphospholipid syndrome (APS) was researched in 57 children and adolescents with systemic lupus erythematosus (SLE). The frequency of aPL antibodies was 75.4% (anticardiolipin 70.2% and lupus anticoagulant 29.1%). The positivity for these antibodies fluctuated during the course of the disease. No association was found between aPL antibodies and clinical or laboratory manifestations or the autoantibodies studied, nor with the activity or gravity of the SLE. APS was diagnosed in 14% of the cases (eight patients), on average three years after the diagnosis of SLE. Four patients had arterial thrombosis (stroke, three; transient ischaemic attack, one; amaurosis fugax, two; renal, one), one presented with deep vein thrombosis (DVT) and three had involvement of small calibre vessels (osteonecrosis, two; transverse myelitis, one). Recurrences were observed in three of the eight cases (37.5%), with a mean interval of 13 months between the events. The presence of APS was associated with haemolytic anaemia, leukopenia, thrombocytopenia, coagulation abnormalities, ischaemic cerebrovascular accidents, amaurosis fugax, osteonecrosis and interstitial pneumonitis. A negative association was observed between APS and the presence of anti-Ro antibodies.
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PMID:Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and adolescents with systemic lupus erythematosus. 1466 97

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.
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PMID:[Anagrelide in the treatment of thrombocythemia essential (ET)]. 1596 9

(1) Chemotherapy does not appear to prolong the survival of patients with inoperable pleural mesothelioma, and the tumour response rate barely exceeds 20%. A combination of cisplatin + doxorubicin seems to provide the best response rates. (2) In a trial of second-line docetaxel therapy in patients with non small cell lung cancer, survival was extended by about 3 months compared with palliative care (7.5 versus 4.6 months). (3) Pemetrexed, an antifolate closely related to methotrexate and raltitrexed, has been authorized for use for both conditions. (4) In a randomised single-blind trial involving 456 patients with previously untreated pleural mesothelioma, survival was prolonged by about 3 months by a cisplatin + pemetrexed combination in comparison with cisplatin + placebo (12.1 versus 9.3 months). The respective tumour response rates were 41.3% and 16.7%. This is the only available comparative trial of pemetrexed in patients with mesothelioma. A more appropriate comparator would have been a cisplatin-based regimen such as cisplatin + doxorubicin. (5) A "non inferiority" trial of second-line treatment in 571 patients with locally advanced or metastatic non small cell lung cancer showed no significant difference in median survival time with pemetrexed versus docetaxel (about 8 months with both treatments). However, this trial does not rule out the possibility that pemetrexed is less effective than docetaxel. (6) Supplementation with folic acid and vitamin B12 reduces haematological and gastrointestinal complications associated with the antifolate activity of pemetrexed. (7) Despite this supplementation, more than 15% of patients in the mesothelioma trial developed severe neutropenia, leukopenia or fatigue during cisplatin + pemetrexed therapy. Pemetrexed aggravates the nausea and vomiting provoked by cisplatin, a drug that is highly emetic. (8) The adverse effects of pemetrexed were similar to those of docetaxel in the trial comparing the two drugs. However, neutropenia (5% versus 40%) and febrile neutropenia (2% versus 13%) occurred less frequently with pemetrexed. (9) Patients receiving pemetrexed must be monitored closely for some rare but potentially severe adverse effects; they include angina, myocardial infarction and stroke, liver damage, and bullous skin rash. (10) According to the summary of product characteristics (SPC), pemetrexed therapy must be administered in combination with folic acid and vitamin B12 supplementation in order to reduce haematological toxicity, and also with corticosteroid therapy to reduce the risk of serious skin reactions. (11) In practice, given the absence of a better alternative, and pending the results of a second trial, the cisplatin + pemetrexed combination can be used as a first-line regimen for patients with pleural mesothelioma. However, pemetrexed cannot replace docetaxel in second-line treatment of non small cell lung cancer.
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PMID:Pemetrexed: new drug. Pleural mesothelioma: a first encouraging trial. 1640 Jul 41


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