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)

Between November 1987 and September 1989, 419 cadaveric renal transplants were performed at our university. Of the patients 36 (8.6%) had invasive cytomegalovirus infection documented by gastric or duodenal mucosal biopsy in 23 (64%), bronchoalveolar lavage in 12 (33%), allograft biopsy or nephrectomy specimen in 5 (14%) and/or liver biopsy in 1 (3%). Cytomegalovirus severity was defined as mild in 27 patients, moderate in 6 and severe in 3. Ganciclovir [9-(1,3-dihydroxy-2-propoxymethyl)-guanine] was begun once the diagnosis was confirmed by histology or culture at a median of 56 days from transplantation (range 28 to 133 days). Duration of ganciclovir therapy was a minimum of 7 days or until fever was absent for 5 consecutive days (mean 12.2 +/- 3.5 days, range 4 to 21). Ganciclovir was well tolerated and side effects were limited to de novo neutropenia (7 patients), thrombocytopenia (2) and rash (1). Initial clinical improvement was observed in all patients. Two patients had recurrent cytomegalovirus infections that responded to a second course of ganciclovir. The 1-year actuarial patient survival was 100%. At a mean followup of 12.7 +/- 6.2 months 19 patients retained allograft function with a mean serum creatinine of 2.5 mg./dl. (range 1.2 to 4.6). Ganciclovir appears to be a safe and effective drug for the treatment of tissue invasive cytomegalovirus infection in cadaver renal transplant recipients. Prompt institution of this drug at diagnosis of invasive cytomegalovirus may lower the mortality rate formerly associated with this disease.
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PMID:Therapeutic use of ganciclovir for invasive cytomegalovirus infection in cadaveric renal allograft recipients. 133 42

Ganciclovir is effective in halting or delaying the progression of cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). However, the development of neutropenia necessitates the interruption of ganciclovir therapy in 40-50% of AIDS patients. In an ongoing randomized, controlled trial, AIDS patients with CMV retinitis are receiving standard ganciclovir therapy or ganciclovir plus recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). rHuGM-CSF is administered by daily subcutaneous injections and is given in ascending doses based on the neutrophil response in the individual patient. Preliminary data obtained from 36 evaluable patients (21 receiving ganciclovir alone, 15 receiving ganciclovir plus rHuGM-CSF) suggest that rHuGM-CSF administration is associated with a trend toward a decrease in the proportion of patients developing an absolute neutrophil count (ANC) of less than 750 cells/microliter (40% vs. 59%), in the overall incidence of such neutropenic episodes (20 vs. 68), and in the duration of ganciclovir treatment interruption due to the development of an ANC of less than 500 cells/microliter (5.5 days vs. 10.1 days). rHuGM-CSF administration has been generally well tolerated, and no consistent proliferative effect of this agent on human immunodeficiency virus infection has been observed. Definitive conclusions regarding the coadministration of rHuGM-CSF and ganciclovir await completion of the trial.
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PMID:Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. 184 18

Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic infection in patients with the acquired immune deficiency syndrome (AIDS), in whom it may cause loss of vision. The early diagnosis of CMV retinitis depends on patient awareness of often subtle clinical symptoms; screening examinations may be of benefit. Aggressive treatment of the condition is imperative. Ganciclovir administered intravenously has been shown to be effective therapy, but treatment must be continued indefinitely and is associated with a risk of neutropenia. Careful monitoring during treatment is required. Investigational methods of treatment, including intravitreal injection of ganciclovir or use of foscarnet, another antiviral agent, may be of benefit if intravenous ganciclovir therapy must be discontinued.
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PMID:Diagnosis and treatment of cytomegalovirus retinitis. 184 24

The clinical manifestations of cytomegalovirus (CMV) infection in persons with AIDS are described, and recent advances in the management of these syndromes with antiviral agents are reviewed. CMV infection is the most common serious opportunistic viral infection in AIDS patients. Clinical manifestations include chorioretinitis, gastroenteritis, hepatitis, pneumonia, CNS infection, adrenalitis, and a wasting syndrome. The diagnosis of CMV infection requires laboratory demonstration of a serologic response to the virus, detection of viral components or products, or isolation of the virus. Ganciclovir is an acyclic nucleoside analogue marketed for the treatment of CMV-related retinitis in immunocompromised hosts. After i.v. ganciclovir induction therapy, more than 80% of patients show improvement or stabilization of retinitis. Relapse is common in AIDS patients, however, and low-dose i.v. maintenance therapy is recommended. The most serious dose-limiting effect is neutropenia. Intravitreal injection of ganciclovir has been well tolerated and efficacious. Ganciclovir has shown some efficacy in the treatment of other life-threatening CMV infections, especially gastroenteritis, but data are limited. Ganciclovir-resistant strains have been reported. Foscarnet, a pyrophosphate analogue with activity against both human CMV and human immunodeficiency virus, is undergoing clinical trials. Foscarnet has shown promise in the therapy of CMV-related retinitis, but results for other CMV infections are disappointing. Nephrotoxicity is the major dose-limiting effect. AIDS patients with sight-threatening and rapidly progressive CMV-related retinitis should be treated with ganciclovir. Foscarnet may offer an alternative when it becomes available. More must be learned about the efficacy of these drugs in the treatment of CMV infection in patients with AIDS.
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PMID:Management of cytomegalovirus infection in patients with acquired immunodeficiency syndrome. 216 89

Treatment of cytomegalovirus (CMV) disease met with limited success until the development of ganciclovir. Favorable clinical responses to ganciclovir have been reported in approximately 80% of immunocompromised patients with CMV retinitis or gastrointestinal disease. CMV pneumonia is more difficult to treat, with therapy benefiting 10%-72% of patients. Ganciclovir must be given parenterally; the dose-limiting adverse event is neutropenia. Patients with AIDS frequently experience relapse and require maintenance therapy. Foscarnet is an attractive anti-CMV drug but must be given parenterally and is completely dependent on renal clearance for elimination. Prevention of CMV disease with antiviral drugs may be possible. Five weeks of intravenous acyclovir (500 mg/m2 three times a day) significantly reduced the risk of CMV infection and disease in seropositive allogeneic bone marrow transplant recipients. The prophylactic benefit of acyclovir has recently been confirmed and extended by a placebo-controlled trial in renal allograft recipients at the University of Minnesota. A 12-week course of high doses of oral acyclovir (3,200 mg/d) was safe and significantly reduced the incidence of CMV infection and disease.
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PMID:Management of cytomegalovirus disease with antiviral drugs. 217 14

Cytomegalovirus (CMV) infections are a common cause of morbidity and mortality in immunosuppressed patients. Ganciclovir is an acyclic deoxyguanosine analog structurally similar to acyclovir but with superior activity against CMV. The median ganciclovir concentration required to inhibit viral replication by 50 percent is 2.15 mumol versus 72 mumol for acyclovir. Pharmacokinetic properties of ganciclovir include biexponential decay with a terminal half-life of 2.5 hours, tissue uptake, cerebrospinal fluid penetration, and renal dependence for elimination. CMV treatment approaches have commonly used dosages of 3-15 mg/kg/d. In uncontrolled trials, the response rate of CMV retinitis is approximately 80 percent. The overall response rate for CMV pneumonitis has been approximately 50 percent. However, AIDS (acquired immunodeficiency syndrome) and other immunosuppressed patients appear to respond more favorably (approximately 70 percent) than do marrow transplant recipients. Relapse is common once ganciclovir is stopped and maintenance therapy may be required for sustained benefit. Neutropenia appears to be the drug-limiting adverse reaction. Although the development of ganciclovir-resistant CMV, risk factors for neutropenia, and alternative administration strategies all need further study, ganciclovir appears to have a role in the treatment of cytomegalovirus disease.
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PMID:Evaluation of ganciclovir for cytomegalovirus disease. 254 66

Cytomegaloviral retinitis was diagnosed in nine eyes of seven patients with acquired immune deficiency syndrome (AIDS) on the basis of the characteristic ocular findings and a positive culture for cytomegalovirus (CMV) obtained systemically. Treatment with ganciclovir was begun on a protocol which provided two weeks of inpatient therapy at daily doses of 2.5 to 10 mg/kg followed by outpatient therapy at a reduced dosage three to six days per week. Outpatient maintenance dosage ranged from 15 mg/kg per week to 30 mg/kg per week. In seven eyes of six patients the treatment decreased retinal inflammation and stabilised the margins of the lesions. Six patients have tolerated long term maintenance therapy for 10-30 weeks. Six of seven patients (85%) in this study developed side effects from ganciclovir which required periods of a reduction in dosage or interruption of therapy. The side effects from ganciclovir included neutropenia, thrombocytopenia, drug fever, and neuropathy. Physicians using ganciclovir in AIDS patients must watch for the signs of drug toxicity and adjust treatment accordingly. Ganciclovir appears to be a promising therapy for CMV retinitis, but further work is necessary to determine the best regimen for optimal efficacy with minimal side effects.
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PMID:Long-term outpatient treatment of CMV retinitis with ganciclovir in AIDS patients. 255 8

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.
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PMID:Treatment of cytomegalovirus retinopathy with ganciclovir. 282 64

Eighteen immunocompromised patients with cytomegalovirus (CMV) retinitis were treated with ganciclovir, an investigational antiviral drug. CMV retinitis in association with acquired immune deficiency syndrome (AIDS) developed in 17 patients; CMV retinitis developed in one patient after cardiac transplantation. Fourteen patients responded to ganciclovir treatment with improvement in CMV retinitis. In 11 patients, the response was classified as complete; in three patients, the response was partial. Continued improvement in the retinitis was often seen while the patient was on maintenance treatment. Maintenance ganciclovir therapy was required; relapse occurred in five of seven patients in whom ganciclovir treatment was interrupted. The major limiting toxic side effect of ganciclovir was neutropenia, which necessitated temporary discontinuation of ganciclovir in five patients but was reversible in all cases. Ganciclovir appears to be an effective therapy for CMV retinitis, but chronic maintenance therapy is required.
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PMID:Treatment of cytomegalovirus retinitis with ganciclovir. 282 65

The clinical and virologic efficacy of ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) in the treatment of severe CMV infections in solid organ transplant recipients was investigated. Twelve patients (9 liver and 3 kidney transplant recipients) with CMV retinitis, esophagitis, hepatitis, or pneumonia received ganciclovir at a dose of 0.75-7.5 mg/kg/day for 10-30 days (mean duration 17 days). Clinical stabilization or improvement occurred in 8 patients (67%). Serial liver biopsies in 6 liver allograft recipients with CMV hepatitis demonstrated substantial histologic improvement on treatment. Of 6 patients with CMV pneumonia, 4 (67%) recovered and survived. Cultures of blood and other sites became negative in 9 patients (75%). Three patients (25%) had recurrent viral shedding after treatment, but none of these relapsed with invasive infections. Mild neutropenia was the only side effect encountered but was frequent (67%). The overall survival rate was 50%. Ganciclovir is effective in reducing CMV shedding in solid organ transplant recipients and is well tolerated. Our experience suggests a clinical benefit as well in patients with severe, invasive CMV disease. Relapse, in contrast to patients with the acquired immunodeficiency syndrome, is infrequent.
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PMID:Ganciclovir therapy of severe cytomegalovirus infections in solid-organ transplant recipients. 283 16


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