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)

Standard chemotherapy for disseminated germ cell tumors (GCT) cures most patients but causes considerable acute toxicity, including treatment-related death due to septicemia during neutropenia and pulmonary fibrosis. In addition, chronic and delayed toxicities, particularly Raynaud's phenomenon, have been reported in 6% to 37% of treated patients. In an attempt to minimize the acute and chronic effects of treatment which are related primarily to vinblastine and bleomycin, a randomized trial comparing the efficacy and toxicity of vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin (VAB-6) and etoposide + cisplatin (EP) was conducted on 164 eligible patients with good-prognosis GCT. Seventy-nine of 82 (96%) patients receiving VAB-6 and 76/82 (93%) receiving EP achieved a complete remission (CR) with or without adjunctive surgery. Similar proportions of patients in both arms were found at surgery to have necrosis/fibrosis or mature teratoma. With a median follow-up of 24.4 months in the VAB-6 arm and 25.9 months in the EP arm, the total, relapse-free, and event-free survival distributions were similar in the two arms. Patients receiving EP experienced less emesis (P = .05), higher nadir WBC (P = .06) and platelet counts (P = .01), less magnesium wasting (P = .0001), less mucositis (P = .09), and no pulmonary toxicity. No treatment-related mortality was observed. EP is an efficacious and less toxic regimen and is recommended for good-prognosis patients with disseminated GCT.
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PMID:A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. 245 57

The Radiation Therapy Oncology Group conducted a Phase III single blind trial to evaluate the addition of Levamisole to post-operative thoracic irradiation (200 cGy five times weekly to a total of 5000 cGy plus 1000 cGy boost) in patients with resected RTOG Stage II-III non-small cell lung cancer with positive nodes. Between February 1980 and February 1983, 74 patients from 18 RTOG institutions were randomized; accrual to this study was prematurely terminated due to poor accrual and the inferior survival observed in the levamisole-treated patients on another RTOG trial. Sixty-four patients were evaluable; 32 assigned to levamisole and 32 were assigned to placebo. Over 95% of the patients have been followed for a minimum of 4 years or to death. Two patients on placebo and 5 on levamisole experienced Grade 3 pneumonitis or esophagitis; 1 patient on placebo and 2 on levamisole experienced Grade 3 pulmonary fibrosis. Three patients on levamisole experienced other Grade 3 or 4 toxicity: 1 case of intractable nausea and vomiting and 2 with Grade 4 neutropenia (less than 500 per mm3). There were no fatal complications. Median disease-free survival was 13 months in the placebo group and 9 months for the levamisole group. Median time to distant metastases was 18 and 12 months, and median survival was 20 and 13 months, respectively. We concluded that this study failed to demonstrate an advantage for levamisole.
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PMID:Post-operative thoracic irradiation with or without levamisole in non-small cell lung cancer: results of a Radiation Therapy Oncology Group Study. 282 70

Pulmonary aspergillosis has recently been described as an emerging infection in patients with acquired immune deficiency syndrome (AIDS), but the pathological changes have not been well documented. In this autopsy study, 17 cases of AIDS-related pulmonary aspergillosis were identified from the files of two institutions. With the exception of hypersensitivity reactions, the entire spectrum of pulmonary aspergillosis was represented. Thirteen patients exhibited acute invasive aspergillosis, and seven patients had evidence of subacute or chronic invasive infection, four of whom also had areas of acute invasion. One patient had necrotizing bronchial aspergillosis as well as acute invasive infection, and one individual had saprophytic colonization of a cavity caused by previous Pneumocystis carinii pneumonia (PCP) without evidence of invasive aspergillosis. The same conditions known to predispose immunocompromised individuals without human immunodeficiency virus (HIV) infection to invasive pulmonary aspergillosis were also identified in these patients with AIDS and included neutropenia, steroid therapy, and underlying lung disease. Additional pulmonary conditions were identified in all but one case and consisted mainly of infection or some form of chronic lung disease. In particular, half of the cases were associated with pulmonary fibrosis related to prior PCP. All cases occurred in or after 1990, confirming the perception of the recent emergence of aspergillosis in AIDS. As suggested by this study, one reason for this may be that patients with AIDS are now living long enough to develop one or more of the predisposing conditions for pulmonary aspergillosis.
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PMID:Pulmonary aspergillosis in acquired immune deficiency syndrome: autopsy study of an emerging pulmonary complication of human immunodeficiency virus infection. 938 32

Among all 140 eligible cases in the two late phase II studies of gemcitabine monotherapy for advanced non-small cell lung cancer, response rate was 26.3% in 57 elderly patients group who were older than 70 and 21.7% in 83 non-elderly patients group who were blow 69. Median survival was 9.8 months and 9.3 months for elderly and non-elderly respectively, 1 year survival rate was 35.1% for elderly and 38.6% for non-elderly, and both groups showed good efficacy. Among elderly group, one case died from septic shock accompanied with grade 4 of leukopenia, neutropenia and thrombocytopenia, and two cases developed interstitial pneumonitis. Of these two cases, one with mild pulmonary fibrosis died of respiratory failure due to aggravation of interstitial pneumonitis. Grade 3 or more anemia was occurred significantly more often in elderly group (elderly: 24.6%, non-elderly: 12.0%). There was no significant difference between both groups in the incidence of grade 3 or more of leukopenia and gastrointestinal toxicity, which were relatively low. No significant difference between both groups was found in total gemcitabine doses, average of single dose and the number of administration. Gemcitabine can be administered in elderly cases as well as in non-elderly cases. The results suggested that this agent is well-tolerated and effective for elderly patients with normal organ functions.
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PMID:[Gemcitabine in the treatment of non-small cell lung cancer for elderly patients]. 1039 15

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS.
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PMID:Pulmonary renal syndrome: a 4-year, single-center experience. 1177

Pneumonia and sepsis during neutropenia are common complications from chemotherapy and they are sometimes lethal. Radiation pneumonitis is also a common toxicity after thoracic radiotherapy, and severe pneumonitis causes hypoxia and death. However, the incidence and risk factors of treatment-related death from the treatment of advanced cancer using chemotherapy and/or thoracic radiotherapy are not well understood. Between July 1992 and December 1997, 1799 patients were diagnosed as having lung cancer and 784 of 1799 patients received chemotherapy in the National Cancer Center Hospital East. Of 784 patients, 18 (2.3%) died from toxicity of the initial chemotherapy. In the Japan Clinical Oncology Group (JCOG) trials for lung cancer, 29 of 1176 patients (2.5%) were reported to have died from toxicity of the treatments. Several papers have reported the risk factors of early death after chemotherapy or treatment-related death caused by chemotherapy in patients with cancer. Only poor performance status was a vigorous risk factor. Reported mortality rates of radiation pneumonitis range from 0 to 9.9% from 7 reports and 29 of 1244 patients (2.3%) died of pneumonitis after thoracic radiotherapy or chemoradiotherapy. Our previous report suggested that pulmonary fibrosis identified on plain chest X-ray film is a very strong risk factor of treatment-related death from radiation pneumonitis. At least 1-2% mortality should be expected for chemotherapy and thoracic radiotherapy. And in patients with poor PS, the expected mortality rate from chemotherapy is increased.
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PMID:Treatment-related death from chemotherapy and thoracic radiotherapy for advanced cancer. 1209 34

Hermansky-Pudlak syndrome (HPS) has evolved into a group of genetically distinct disorders characterized by oculocutaneous albinism, a storage pool deficiency, and impaired formation or trafficking of intracellular vesicles. HPS-1 results from mutations in the HPS1 gene and affects approximately 400 individuals in northwest Puerto Rico due to a 16-bp duplication in exon 15. Another 13 mutations have been reported in non-Puerto Ricans. HPS1 codes for a 79.3 kDa cytoplasmic protein of unknown function. HPS-1 patients typically develop fatal pulmonary fibrosis in their fourth decade. HPS-2 is caused by mutations in ADTB3A, which codes for the beta3A subunit of the adaptor protein-3 complex, AP3. This coat protein complex has been localized to the TGN as well as to a peripheral endosomal compartment. Evidence indicates that AP3 plays a role in the stepwise process of vesicular trafficking which leads to formation of the melanosomal, platelet dense body and lysosomal compartments. All three known HPS-2 patients had childhood neutropenia and infections. HPS-3 results from mutations in HPS3 and affects central Puerto Ricans homozygous for a 3904-bp deletion removing exon 1. At least 8 non-Puerto Rican patients have other HPS3 mutations, including an IVS5+1G->A splicing mutation in five Ashkenazi Jewish patients. HPS3 codes for a 113.7 kDa protein of unknown function. HPS-3 manifests with mild hypopigmentation and bleeding. All types of HPS are diagnosed by whole mount electron microscopic demonstration of absent platelet dense bodies, and molecular diagnoses are available for the Puerto Rican HPS1 and HPS3 founder mutations. Mouse and Drosophila models provide candidates for new genes causing HPS in humans. These genes will reveal the pathways by which specialized vesicles of lysosomal lineage arise within cells.
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PMID:Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. 1212 11

This phase II trial evaluated the efficacy and toxicity of weekly docetaxel as treatment of advanced metastatic breast cancer patients resistant to prior anthracycline chemotherapy. After the first 18 patients, the initial dose (40 mg/m2, 30-min i.v. infusion for 6 consecutive weeks, followed by 2-week rest) was reduced to 36 mg/m2 in the remaining 17 patients due to the incidence of toxicity (28% grade 3-4 asthenia). Overall response rate was 34% (95% CI, 19-50): two complete (6%) and ten partial responses (28%) were found. The median duration of response was 6.8 months, the median time to disease progression was 8.4 months, and the median overall survival was 13.6 months (median follow-up of 11.4 months). Neutropenia was the only severe hematologic toxicity (17% of patients), whereas asthenia, nail, ocular and skin disorders were the most common nonhematologic toxicities. Only one death during further follow-up was related to toxicity (caused by pulmonary fibrosis). In conclusion, we found weekly docetaxel to be an active and safe chemotherapy regimen for patients with metastatic breast resistant to previous anthracyclines. This weekly regimen caused minimal myelosupression, while retaining significant activity against advanced breast cancer. Both factors provide attractive possibilities for the development of combination therapies incorporating weekly docetaxel. Nevertheless, the number of patients receiving either dose (40 and 36 mg/m2) which we studied is low and our results require confirmation on larger groups of patients.
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PMID:Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment. 1279 98

The Hermansky-Pudlak syndrome (HPS) is a collection of related autosomal recessive disorders which are genetically heterogeneous. There are eight human HPS subtypes, characterized by oculocutaneous albinism and platelet storage disease; prolonged bleeding, congenital neutropenia, pulmonary fibrosis, and granulomatous colitis can also occur. HPS is caused primarily by defects in intracellular protein trafficking that result in the dysfunction of intracellular organelles known as lysosome-related organelles. HPS gene products are all ubiquitously expressed and all associate in various multi-protein complexes, yet HPS has cell type-specific disease expression. Impairment of specialized secretory cells such as melanocytes, platelets, lung alveolar type II epithelial cells and cytotoxic T cells are observed in HPS. This review summarizes recent molecular, biochemical and cell biological analyses together with clinical studies that have led to the correlation of molecular pathology with clinical manifestations and led to insights into such diverse disease processes such as albinism, fibrosis, hemorrhage, and congenital neutropenia.
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PMID:Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. 1642 Feb 44

Systemic sclerosis (scleroderma) is a connective tissue disorder of unknown aetiology characterised by immune abnormalities, which has been related to an increased risk of malignancy. Lung cancer is the most prevalent among these patients. We present a clinical case of a 42 years old non smoker female with systemic sclerosis. She presented progressive general health status worsening and an exudative pleural effusion, with no evidence of infection or malignancy. Chest high resolution computed tomography revealed pulmonary fibrosis. Bronchoscopy, bronchial and bronchoalveolar lavage were normal. Extra- -pulmonary malignancies were excluded. Pleural nodularities were found on pleuroscopy and the biopsy was compatible with lung adenocarcinoma. Chemotherapy was then started, which complicated with febrile neutropenia, sepsis and patient death 12 days after. The purpose of this case report is to bring attention to the relationship, although rare, between systemic sclerosis and lung cancer, stressing the importance of adequate pulmonary surveillance in these patients.
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PMID:[Lung adenocarcinoma associated with systemic sclerosis: a case report]. 1914 91


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