Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Central nervous system (CNS) infections in immunocompromised hosts are often accompanied by subtle disorders because immunosuppression usually decreases the inflammatory response. CNS infections in immunocompromised patients are usually caused by organisms different from those found in the general population. The organism causing CNS infection in an immunocompromised host can often be predicted if the type of immune abnormality of the patient is known. The common causes of CNS infection in immunocompromised hosts are reviewed here. Meningitis in patients with neutropenia is usually due to enteric Gram negative bacilli that live in the patient's own digestive tract. Pseudomonas aeruginosa is most common and is followed by E. Coli, Klebsiella, Enterobacter and Proteus. A major risk in patients with abnormal immunoglobulins or splenectomy is infection with encapsulated bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Meningitis caused by any of the encapsulated bacteria can be fulminant. Listeria monocytogenes is the most common cause of bacterial meningitis in patients with impaired cellular immunity. Nocardia asteroides is a leading cause of brain abscess in patients with hematologic malignancy. Most patients have evidence of concomitant pulmonary lesions. Fungi are among the most common organisms involving the CNS in immunocompromised hosts. Susceptible patients include those with lymphoma or leukemia and those who receive therapies aimed at suppressing delayed hypersensitivity. Cryptococcus neoformans is a common fungal cause of CNS infection in immunocompromised hosts. The primary site of infection is the lung. Spread to the CNS is via the blood stream. The clinical course is highly variable: meningitis, meningoencephalitis and focal mass lesions. Candida causes meningitis or meningoencephalitis characterized by multiple small abscesses in neutropenic hosts. Organisms reach the CNS via the blood stream usually from the digestive tract or infected intravenous catheters. Aspergillus causes brain abscess, cerebral infarction and focal meningitis in patients with neutropenia. The primary infection is in the lung. The parasites that infest the CNS of immunocompromised patients are usually those that exploit a T-lymphocyte, mononuclear phagocyte host defect. The most common are Toxoplasma gondii and Strongyloides stercoralis. There have been a few cases of amebiasis with dissemination to the brain in patients with hematologic malignancies. Toxoplasma gondii causes major CNS disease in immunocompromised hosts: meningoencephalitis or mass lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Infections of the central nervous system in malignant hemopathies]. 372 88

The most significant impact on cerebral infarction comes from the primary prevention of the processes that lead to stroke in at-risk individuals prior to the development of symptoms. Antithrombotic therapy with warfarin or aspirin significantly reduces thromboembolic risk in non-valvular atrial fibrillation. The failure of primary preventive measures and the progression of disease is heralded by the development of cerebral or retinal ischaemic events; the majority of clinical trials investigating stroke prevention have targeted the secondary prevention of stroke in patients with ischaemic symptoms. A 25% risk reduction has been demonstrated with antiplatelet therapy. This was typically aspirin 1000 to 1300 mg/day, but more recently even lower doses have been beneficial, with lower rates of minor and major bleeding. Ticlopidine has demonstrated efficacy in the secondary prevention of stroke after transient ischaemic attacks and completed stroke, with a 2% risk of significant neutropenia. The benefits of carotid endarterectomy have been demonstrated in patients with symptomatic internal carotid artery stenosis involving 70 to 99% of the arterial diameter. Surgery is not indicated in patients with less than 30% internal carotid artery stenosis; 30 to 69% continues to be studied. When primary and secondary preventive measures have failed, strategies directed at managing acute focal cerebral ischaemia include re-establishing cerebral blood flow and limiting ischaemic neuronal injury. Advances in basic research that have identified components of the ischaemic cascade have been translated clinically into numerous clinical trials, each targeted to one or sometimes two steps in the hope of improving neuronal salvage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylaxis and treatment of stroke. The state of the art in 1993. 768 4

The established treatment for multiple myeloma (MM) comprises induction with infusional chemotherapy, high dose chemotherapy (HDC) and autologous transplantation followed by maintenance interferon. On relapse, patients (pts) are reconsidered for this however some are unsuitable and in this situation the therapeutic options are limited. Between June 1995 and May 1997, 14 pts with previously treated relapsed or refractory MM were recruited. Using a prospective database, the tolerability and efficacy of chronic low dose oral idarubicin was evaluated. The median age of pts was 63 years. All had received previous anthracycline in the form of infusional cVAMP chemotherapy. 11/14 had received previous HDC. Median time from diagnosis to commencing idarubicin was 77 months. 10 mg idarubicin was administered 3 times/week for 3 weeks of a 5 week cycle. The maximum number of courses was 6. Three pts completed 6 courses, 5 pts 3 courses, 2 pts 2 courses and 4 pts 1 course. The reasons for stopping treatment were death due to progressive disease (PD) in 7 pts, persistent thrombocytopenia in 2 pts, PD in 1 pt and 1 pt suffered a cerebral infarction not considered to be related to the idarubicin therapy. Two pts showed evidence of response, neither amounting to a partial response. One had stabilisation of paraprotein with a reduction in bone marrow infiltration (47% to 7% plasma cells), the other had a reduction in bone marrow infiltration after 3 course but an increase after 6 courses. In total forty-one courses of treatment were administered. Grade 3/4 haematological toxicities were noted in a minor fraction of cases and were as follows: anaemia 6/41, neutropenia 10/41 and thrombocytopenia 11/41. Our data therefore shows a minor response in 2/14 (14%) of heavily pretreated patients with MM, without evidence of severe toxicity. It provides the rationale for using oral idarubicin as either single agent or in combination therapy for patients earlier on in their disease course especially if they are unsuitable for standard therapy.
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PMID:Oral idarubicin as a single agent therapy in patients with relapsed or resistant multiple myeloma. 1060 97

An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin. Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started. After initial defervescence, fever relapsed 2 days after the onset of neutropenia. The CT scan of the lung was consistent with an invasive fungal infection. Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later. The fever persisted and the patient suddenly developed progressive neurological symptoms. CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis. Six days after the onset of neurological symptoms cerebral death was diagnosed. Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain. Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis. In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae. This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain.
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PMID:Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis. 1096 35

Multiple myelomas often occur in elderly people with complications due to aging. A 54-year-old man was first admitted with cerebral infarction, and multiple myeloma (IgG kappa, stage IIIA) occurred in November 1989 that was followed by partial remission after chemotherapy. The karyotype of the bone marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg, vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed in February 1999 because of aggravation of the myeloma. After daily subcutaneous injection of 50 micrograms of nartograstim for six days to treat neutropenia, soft tissues around the right eye were swelled gradually without redness, accompanied by elevation of the serum creatine-kinase concentration. The swelling disappeared, and the enzyme level normalized after discontinuation of nartograstim. In July, on the sixth day of daily subcutaneous injection of 75 micrograms of filgrastim after the same chemotherapy, similar swelling of the soft tissues around the left eye became evident, and again this proved reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day subcutaneous-injection of 75 micrograms of filgrastim daily, the right subclavicular soft tissue became swollen. He died of myocardial infarction, and autopsy revealed infiltration of myeloma cells into the right subclavicular muscle and bone marrow packed with myeloma cells. This case suggests that myeloma cells can proliferate and infiltrate into soft tissues on exposure to granulocyte-colony stimulating factors.
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PMID:[A case of multiple myeloma with infiltration into skeletal muscle after injections of a granulocyte-colony stimulating-factor]. 1218 9

Vinorelbine and gemcitabine are two active single agents with mild toxicity profiles that are used in the treatment of non-small-cell lung cancer (NSCLC). Whether or not very old NSCLC patients, such as those aged 80 years or older, should still be considered for chemotherapy is unknown, since their response to the treatment is also unknown. A phase II clinical trial was conducted to evaluate the efficacy and toxicity of vinorelbine plus gemcitabine in very old patients with inoperable (stage IIIb or IV) NSCLC. Vinorelbine 20 mg/m(2) was given as a 10-min intravenous infusion, followed by a 30-min intravenous infusion of gemcitabine 800 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. From March 1998 to December 2001, 20 patients (16 males, four females) were enrolled in the study. The median age was 83 years, within the range 80-88 years. The median number of treatment cycles per patient was four. With the exception of one, all patients received at least two cycles of treatment. Thirteen patients achieved a partial response, with an overall response rate of 65% (95% confidence interval, 44.1-85.9%). Median survival was 10 months. The significant (WHO grade 3/4) toxicities were myelosuppression, including leukopenia in five (25%) patients, neutropenia in eight (40%), anaemia in six (30%), and thrombocytopenia in three (15%) patients. Febrile neutropenia occurred in two patients and accounted for one treatment-related death. Non-haematological toxicity was generally mild, except one patient who suffered from grade 3 interstitial pneumonitis. Another patient suffered from a cerebral infarction after three cycles of treatment. In conclusion, the combination of vinorelbine and gemcitabine in very old patients with advanced NSCLC is a highly active regimen with an acceptable toxicity profile.
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PMID:A phase II trial of vinorelbine plus gemcitabine in previously untreated inoperable (stage IIIb/IV) non-small-cell lung cancer patients aged 80 or older. 1271 Nov 25

1. The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. 2. This study was undertaken to investigate whether pharmacological neutropenia could modify the postischemic endothelial dysfunction in comparison to smooth muscle whose impairment is likely more related to reperfusion and oxidative stress. 3. A cerebral ischemia-reperfusion by endoluminal occlusion of right middle cerebral artery (MCA) was performed 4 days after intravenous administration of vinblastine or 12 h after RP-3 anti-rat neutrophils monoclonal antibody (mAb RP-3) injection into the peritoneal cavity, on male Wistar rats with 1-h ischemia then followed by 24-h reperfusion period. Brain infarct volume was measured by histomorphometric analysis and vascular endothelial and smooth muscle reactivity of MCA was analysed using Halpern myograph. 4. Neutropenia induced a neuroprotective effect as demonstrated by a significant decrease of brain infarct size. In parallel to neuroprotection, neutropenia prevented postischemic impairment of endothelium-dependent relaxing response to acetylcholine. In contrast, smooth muscle functional alterations were not prevented by neutropenia. Ischemia-reperfusion-induced myogenic tone impairment remained unchanged in vinblastine and mAb RP-3-treated rats. Postischemic Kir2.x-dependent relaxation impairment was not prevented in neutropenic conditions. The fully relaxation of smooth muscle response to sodium nitroprusside was similar in all groups. 5. Our results evidenced the dissociate prevention of pharmacologically induced neutropenia on postischemic vascular endothelial and smooth muscle impairment. The selective endothelial protection by neutropenia is parallel to a neuroprotective effect suggesting a possible relationship between the two phenomena.
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PMID:Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion. 1570 30

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.
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PMID:Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents. 1621 Dec 3

Docetaxel, ifosfamide and cisplatin have proven activity in a broad range of solid tumours and interfere with different phases of the cell cycle. We performed a phase I study with the aim to determine the maximum tolerated dose (MTD) of docetaxel, ifosfamide and cisplatin in patients with solid tumours and to define the safety, dose-limiting toxicity (DLT) and the recommended dose and administration schedule of docetaxel, ifosfamide and cisplatin for further phase II testing. Docetaxel was given by 1-h infusion on day 1, followed by ifosfamide 1000 mg/m(2)/day as a continuous infusion for 5 days. Mesna was added at the same doses to the same infusion bag and was continued for 12 h after the end of ifosfamide. Cisplatin was administered as a 24-h infusion concomitantly with ifosfamide, but in separate infusion bags, either on day 5 (schedule A) or on day 1 (schedule B). Escalation steps were planned only for docetaxel (60, 75, 85 mg/m(2)) and cisplatin (50, 75, 100 mg/m(2)). No intrapatient dose escalation was permitted. Prophylactic ciprofloxacin was used after a protocol amendment was implemented. No prophylactic haematopoietic growth factors were used. Cycles of docetaxel, ifosfamide and cisplatin were given at 3-week intervals. Toxicity was scored according to National Cancer Institute Canada-Common Toxicity Criteria 2. The MTD was defined as the dose at which a DLT was observed in fewer than two of six patients during the first treatment cycle. In total, 85 patients received 309 cycles. Only three escalation steps could be explored and DLTs were observed at each dose level. In total, 32 patients and 49 cycles showed DLTs. Febrile neutropenia occurred in 20 patients (24%). Only two DLTs were nonhaematological (one cerebral infarction and one encephalopathy grade 4). Neutropenia grade 4 lasted for greater than 7 days and/or thrombocytopenia grade 4 was dose limiting in 10 patients. Febrile neutropenia occurred in five of 41 patients (12%) who received prophylactic ciprofloxacin and in 15 of 44 patients (34%) who did not. MTD was reached at level 3 (docetaxel, 75 mg/m(2) and cisplatin, 75 mg/m(2)). With a lower dose of docetaxel (60 mg/m(2)) both schedules A and B were feasible, although, overall, schedule A seemed to be better tolerated. On the basis of this phase I study, the recommended docetaxel, ifosfamide and cisplatin regimen is docetaxel (60 mg/m(2)) on day 1, ifosfamide (1000 mg/m(2)/day) on days 1-5 and cisplatin (75 mg/m(2)) given on day 5. It is associated with substantial haematological toxicity, but this is feasible provided prophylactic antibiotics are used.
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PMID:Docetaxel, ifosfamide and cisplatin in solid tumour treatment: a phase I study. 2008 71

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel (DOC) treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study (9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m(2) per day for 14 days, and DOC 40-50mg/m(2) by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade II a, 4 cases Grade II b, 1 case Grade IV a, and 4 cases Grade IV c. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.
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PMID:[Evaluation of combination chemotherapy with oral S-1 administration followed by docetaxel by superselective intra-arterial infusion for patients with oral squamous cell carcinomas]. 2156 36


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