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Query: UMLS:C0027947 (neutropenia)
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Fungal infections are increasing in frequency, especially among patients with haematological malignancies. The fungi which cause most of the infections in cancer patients are Candida spp. and Aspergillus spp. These fungi seldom infect individuals with normal host defence mechanisms. Many factors predispose patients to fungal infection, including neutropenia, lymphopenia, gastro-intestinal ulceration, intravenous catheters and adrenal corticosteroid therapy. Candida spp. cause 5 major types of infection: dermatitis, thrush, gastro-intestinal, primary organ and disseminated infection. Aspergillus spp. and Phycomycetes cause pulmonary, disseminated or rhino-cerebral infection. Cryptococcus neoformans usually causes meningitis but may cause pneumonia or disseminated infection. The diagnosis of fungal infection is often made only at postmortem examination, because it is difficult to isolate the aetiological agent from sites of infection. Amphotericin B remains the mainstay of antifungal therapy, but is seldom effective in the patient with compromised host defences. Successful management of these infections in the future will depend upon improvement in diagnostic capabilities as well as the introduction of more effective and less toxic antifungal agents.
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PMID:Fungal infections in the cancer patient. 60 7

A retrospective review of charts of 156 human immunodeficiency virus-infected children cared for during a 7.5-year period revealed 11 episodes of disseminateed candidiasis (DC) occurring in 11 patients (7%). All 11 patients developed the fungal infection in the context of advanced human immunodeficiency virus infection. All but one were hospital-acquired, occurring at a mean of 2.3 months after admission. Ten patients had been febrile for more than 14 days before diagnosis. Previous oral thrush and central venous catheters (73 and 82% of patients) represented major predisposing factors for development of DC. Neutropenia (2 of 11 patients) did not represent a major risk factor for DC. Candida albicans was isolated in 9 patients, Rhodotorula minuta in 1 patient and 1 fungal isolate could not be identified. Sources of isolation were blood (8 of 11 patients), central venous catheters (3 of 11) and urine (2 of 11). Lungs (6 of 11 patients), esophagus (5 of 11) and brain, heart and kidneys (3 patients each) were the organs most often involved in DC. Antemortem diagnosis was achieved in only 7 (64%) patients; none of the 4 patients with DC diagnosed postmortem had been treated before death. Seven patients were treated with amphotericin B; 6 of them died but only 3 were treated for more than 7 days of therapy. The overall mortality was 90% (10 of 11 patients). In all 20% of the 50 human immunodeficiency virus-infected children who died at our hospital during the study period had an episode of DC in close proximity to their death. DC was considered the direct cause of death in 4 of 10 children.
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PMID:Disseminated fungal infections in children infected with human immunodeficiency virus. 176 3

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
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PMID:Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy. 244 31

In 1984 a large prospective study of gay and bisexual men was begun to elucidate the natural history of the human immunodeficiency virus (HIV) infection. At two successive semiannual examinations, clinical or hematologic abnormalities were found up to 13 times more often among HIV-seropositive men (n = 1611) than HIV-seronegative men (n = 2646). More than 30% of the seropositive participants had persistent generalized lymphadenopathy, independent of T-helper lymphocyte (CD4) counts and most other signs and symptoms. Other clinical manifestations such as thrush, anemia, thrombocytopenia, neutropenia, fever, and fatigue occurred with only slightly reduced CD4 counts (400 to 700/mm3) and appeared to increase exponentially with progressively lower counts. A simple systematically derived clinical index using these manifestations identified more than 70% of the seropositive men with significant T-helper cell depletion. This kind of clinical index may be useful for assessing groups of HIV-infected persons, especially those whose T-lymphocyte numbers and function cannot be readily measured.
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PMID:Infection with the human immunodeficiency virus: clinical manifestations and their relationship to immune deficiency. A report from the Multicenter AIDS Cohort Study. 295 44

Using serial examination and oral cytology, 50 adult patients undergoing induction therapy for acute leukemia were studied for oral colonization with candida species. Ninety percent of patients were found to be colonized with Candida, with most of these colonizations present by day 14. The 30 patients exhibiting colonization with pseudohyphae received ketoconazole 400 mg daily by mouth. Of 20 patients in this group treated for 5 or more days, Candida organisms were eradicated in nine. Sixteen patients from the above group with persistent colonization on ketoconazole were treated by independent clinical decision for sustained fever and neutropenia with Amphotericin B, but only one responded by elimination of colonization. Seven of the 15 patients who did not initially receive ketoconazole developed Candida dissemination in contrast to two of 30 who received ketoconazole initially (P = 0.003, Fisher's exact test). No patient who initially had or acquired a negative cytology developed oral or disseminated candidiasis. Clinical oral candidiasis occurred in three patients, all of whom were receiving amphotericin B. Approximately 90% of these patients have or develop oral colonization with Candida organisms as identified by oral cytology. Those with colonization, both with and without pseudohyphae present, are at risk for dissemination. Amphotericin B does not eliminate colonization remaining after treatment with 400 mg of ketoconazole daily. More effective diagnostic and therapeutic strategies are needed to identify and eliminate Candida organisms and to prevent disseminated candidiasis in this population of patients.
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PMID:The pathogenesis and clinical significance of cytologically detectable oral Candida in acute leukemia. 316 16

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS).
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PMID:Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study. 777 82

The clinical files were reviewed of eight pediatric patients who died between 1976 and 1990, having the pathological diagnosis of aspergillosis. During the clinical evolution seven displayed malnutrition and respiratory symptomatology, four had slow evolving fever and oral candidiasis. The image in all the chest X-Rays was opaque. In the laboratory four had leukopenia, lymphopenia and neutropenia: two with a positive culture of Aspergillus. Five received four to eight different antibiotics during the last clinical evolution. All showed a combination of diverse forms of aspergillosis, all with the invasive form, five with the disseminated form, three bronchopulmonary allergic and one with aspergilloma. All had invasion of the respiratory system. Septicemia had the cause of death in four and three was direct relation with Aspergillosis.
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PMID:[Pulmonary aspergillosis. Report of 8 children]. 858 74

All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic in a 5-year period were reviewed and compared against other patients attending the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration. 89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis (ANUG) and responded well to conventional treatment for ANUG. The cases were compared with 269 controls in logistic regression. Gingival ulceration was associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly due to a protective effect of co-trimoxazole medication. 5 patients with neutropenia had extensive ulceration without the microflora of ANUG. Histopathology, viral and bacterial culture revealed non-specific changes. The ulcers did not respond to the treatment regimen for ANUG but responded to treatment of their neutropenia. Gingival ulceration is not common in HIV infection. Most cases resemble severe ANUG. It is more frequent in younger people, those with oral candidiasis and without AIDS. Co-trimoxazole may be protective. A minority of cases with ulceration and associated neutropenia resembled the non-specific oral ulceration associated with HIV.
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PMID:Gingival ulceration in HIV infection. A case series and case control study. 954 97

Mucositis, the inflammation and necrosis of mucosal membranes, is a serious and debilitating consequence of many cancer therapies. We were interested in the potential role of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor, r-metHuG-CSF) in the reduction of mucositis. Patients with newly diagnosed small-cell lung cancer (SCLC) were treated with CAE chemotherapy (cyclophosphamide, doxorubicin, and etoposide) and placebo or filgrastim. If patients had an episode of febrile neutropenia, they received unblinded filgrastim in subsequent CAE cycles. Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral candidiasis. Oral mucositis was analyzed using the unadjusted chi-square test, and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model. During cycle 1, placebo-treated patients had more episodes of mucositis (47%) compared with those patients randomized to filgrastim (28%). Across all cycles of treatment, 70% of placebo-treated patients experienced mucositis, compared with 53% of patients randomized to filgrastim. A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim.
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PMID:Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy. 1085 Mar 81


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