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)

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.
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PMID:[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)]. 902 Sep 48

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.
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PMID:[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group]. 902 Sep 49

Kikuchi's disease is a fairly common self-limited disorder among Orientals that usually involves the cervical lymph nodes of young individuals and occurs predominantly in females. Frequently, the disease is associated with fever or flu-like symptoms, an elevated erythrocyte sedimentation rate (ESR), neutropenia, and lymphocytosis with atypical lymphocytes in the peripheral blood, suggesting a viral origin. However, no infectious agent has been identified. The presence of Kaposi sarcoma-associated herpesvirus, known as human herpesvirus 8 (KSHV/HHV 8), was investigated by polymerase chain reaction (PCR) in archival tissue from 26 cases of Kikuchi's disease using published sequences of KSHV/HHV 8 as primers. PCR products were further characterized by Southern blot analysis. Forty reactive lymph nodes and a case of Kaposi sarcoma (KS) were included as negative and positive controls, respectively. Patients consisted of 10 men and 16 women with a mean age of 27 years. All patients were previously healthy and presented with cervical or axillary lymphadenopathy. None were positive for human immunodeficiency virus (HIV) or otherwise immunocompromised. Viral DNA was amplified by PCR in six cases of Kikuchi's disease (23%) and the control KS tissue. Southern blot analysis confirmed that the amplified products were KSHV/HHV 8. In the reactive lymph nodes, no viral genome was amplified by PCR. The presence of DNA sequences of KSHV/HHV 8 in a substantial portion of Kikuchi's disease suggests that KSHV/HHV 8 might play an important role in the pathogenesis of a subset of Kikuchi's disease.
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PMID:Kaposi's sarcoma-associated herpesvirus in Kikuchi's disease. 978 47

Blood count abnormalities are a recognized feature of many viral infections and immunizations but little is known about the haematological effects of influenza vaccination. We report a 67-year-old patient who developed thrombocytopenia and severe neutropenia 3 weeks after she was vaccinated against influenza. The case led us to study prospectively the blood counts of 70 people aged over 65 before and after they received influenza vaccine. There were no significant changes in the levels of haemoglobin, neutrophils, monocytes, eosinophils or platelets after vaccination, but the total WBC counts (mean +/- SD, 6.86 +/- 1.52) and lymphocyte counts (1.69 +/- 0.61) were significantly lower at 4 weeks than at baseline (7.22 +/- 1.60 [P = 0.02] and 1.86 +/- 0.62 [P = 0.001] respectively) and in four subjects the lymphocyte count fell to below 0.7 x 10(9)/l. Since influenza vaccine does not contain live virus, its haematological effects presumably relate to the host immune response rather than to viral replication.
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PMID:Haematological changes associated with influenza vaccination in people aged over 65: case report and prospective study. 980 75

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.
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PMID:A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer. 984 81

We report a 2-year experience with olanzapine treatment (20 mg daily) in a 65-year-old male patient with treatment-resistant paranoid schizophrenia, who had previously developed leucopenia and neutropenia first on clozapine and, subsequently, also on risperidone. Olanzapine seems to be safe in this patient, since no major decreases of haematological parameters were observed. The only exception was a brief decrease of leucocyte and neutrophil (but not erythrocyte or platelet) counts during influenza-like viral infection. However, the control of psychotic symptoms on olanzapine is not as good as on clozapine.
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PMID:Olanzapine appears haematologically safe in patients who developed blood dyscrasia on clozapine and risperidone. 1095 65

The antitumor activity of gemcitabine is not dose-response related but schedule-dependent. Based on the results of a published phase I study in patients with nonsmall-cell lung cancer we started a pilot study of a 24-hr infusion of gemcitabine in patients with adenocarcinoma of the pancreas and biliary tract cancer. Twenty-five patients were enrolled and received a 24-hr infusion of gemcitabine once weekly on three consecutive out of 4 weeks. Dose levels of gemcitabine ranged from 100 to 150 mg/m2. One of 13 chemotherapy-naive patients had a partial response. Dose-limiting toxicity (DLT) was thrombocytopenia in pretreated patients and neutropenia in chemotherapy-naive patients. Other toxicities were oral mucositis, fever, flu-like symptoms, and asthenia. Maximum tolerated dose (MTD), especially in pretreated patients, was 100 mg/m2.
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PMID:Toxicity of a 24-hour infusion of gemcitabine in biliary tract and pancreatic cancer: a pilot study. 1190 37

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
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PMID:Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. 1195 96

The past two decades have witnessed an increase in serious fungal infections, without corresponding growth in available antifungal agents. Voriconazole (VRC) is a novel triazole antifungal, recently approved in Europe for treatment of serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant Candida species. Voriconazole has in vitro activity against yeasts and yeast-like fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and amphotericin B (AMB). Candida albicans is generally the most susceptible yeast (VRC MIC subset90 of 0.06 microg/ml); C. krusei often has low MICs even in the face of FLU/ITC resistance. Voriconazole has demonstrated comparable, or better, in vitro activity than ITC and AMB against Aspergillus (mean MICs 0.19-0.58 microg/ml), Ascomycetes, Bipolaris, Fusarium, Blastomyces dermatitidis, Coccidioides immitis, dermatophytes, Histoplasma capsulatum, Malassezia, and Scedosporium angiospermum (P. boydii). The drug possesses potent fungicidal activity against moulds including Aspergillus, Scedosporium, and Fusarium. Fungicidal activity is likely due to the high affinity of VRC for fungal 14-alpha-demethylase, a concept supported by ultrastructural and biochemical analysis. Animal studies confirmed the activity of VRC against infections including pulmonary and invasive aspergillosis (IA); A. fumigatus endocarditis; fusariosis; pulmonary cryptococcosis; and invasive candidiasis. Most importantly, well-designed human clinical trials have confirmed the efficacy of VRC in the treatment of candidal esophagitis, IA, and febrile neutropenia. Smaller studies and case reports have shown VRC is useful for salvage therapy of IA, cerebral aspergillosis, Scedosporium, and other fungal infections. Clinical testing has shown VRC is safe and well tolerated; the most common side effect is benign, self-limited visual disturbance.
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PMID:Voriconazole -- better chances for patients with invasive mycoses. 1206 15

Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and alfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities.
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PMID:Side effects of therapy of hepatitis C and their management. 1240 99


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