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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Foscarnet and ganciclovir appear to be of similar effectiveness in halting active infection when given as induction therapy and in forestalling progression of disease when given as maintenance therapy in persons with AIDS who have cytomegalovirus (CMV) retinitis. The primary dose-limiting toxicity of foscarnet is nephrotoxicity, whereas that of ganciclovir is neutropenia. The availability of two effective agents with different toxicities permits selection of initial treatment for CMV retinitis based on individual patient characteristics and provides an alternative for therapy if drug intolerance or viral resistance develops. An approach to treatment of first-episode and recurrent CMV retinitis based on patient and drug characteristics is presented. Case reports detailing the use of foscarnet and ganciclovir and problems encountered in patient management are discussed.
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PMID:Therapeutic algorithm for treatment of cytomegalovirus retinitis in persons with AIDS. A roundtable summary. 131 67

The case with the longest survival time (30 months) after the diagnosis of cytomegalovirus retinitis in a group of 53 patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis (median survival time 8.4 months) is described. The patient developed cytomegalovirus retinitis in his left eye and received intravenous virustatic treatment for 29.5 months. Treatment was started with ganciclovir. After withdrawal from maintenance treatment, a relapse of cytomegalovirus retinitis occurred, which was again successfully treated with ganciclovir. A secondary cataract developed, and cataract extraction was performed. After 12.5 months on treatment with ganciclovir, a change to foscarnet was necessary because of neutropenia. Maintenance treatment with foscarnet was well tolerated for 17 months. The cytomegalovirus retinitis showed no signs of reactivation during this period. Vision in the right eye was preserved until death, and no sign of cytomegalovirus retinitis developed in the right eye. This case report demonstrates that an unusual long survival time is possible in a patient sequentially treated with ganciclovir and foscarnet.
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PMID:2.5 years survival with sequential ganciclovir/foscarnet treatment in a patient with acquired immune deficiency syndrome and cytomegalovirus retinitis. 133 12

Among 347 AIDS patients seen at St Mary's Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.
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PMID:Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival. 166 16

Both ganciclovir, a nucleoside analogue, and foscarnet, a pyrophosphate analogue, specifically bind cytomegalovirus (CMV) DNA polymerase and inhibit CMV replication at plasma concentrations achievable with intravenous administration. The agents have similar plasma half-lives, and both are cleared solely by the kidneys. Foscarnet has a low solubility and a high degree of ionization at physiologic pH, requiring it to be administered in higher doses and larger volumes. Both drugs are administered as an initial induction regimen followed by a long-term maintenance regimen. Among patients with the acquired immune deficiency syndrome (AIDS) who have CMV retinitis, the efficacy of long-term maintenance therapy, as measured by median time to retinitis progression, appears to be similar for the two drugs. The major toxicity of ganciclovir is myelosuppression, with dose-limiting neutropenia occurring in approximately 16% and thrombocytopenia in 5% of AIDS patients. The major toxicity of foscarnet is nephrotoxicity, with dose-limiting toxicity occurring in approximately 10-23% of patients; other effects of foscarnet include hypocalcemia, which may be associated with seizure and arrhythmia. Studies in vitro indicate an additive or synergistic inhibitory effect on CMV when these two drugs are combined, suggesting that lower-dose combination regimens or higher-dose alternating regimens may result in greater efficacy with less toxicity than with either drug alone.
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PMID:Approaches to the treatment of cytomegalovirus retinitis: ganciclovir and foscarnet. 184 16

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

Cytomegalovirus retinitis, the most frequently encountered ophthalmologic manifestation of acquired immunodeficiency syndrome (AIDS), emerges in up to 46% of such patients. In the period between april 1989-May 1990, 4 cases of AIDS-related cytomegalovirus retinitis were diagnosed in Singapore and treated at Tan Tock Hospital. Presenting complaints included blurred vision, visual field scotoma, and a field defect. Clinically, cytomegalovirus retinitis is characterized by lesions, usually in the posterior pole, that take the form of fluffy white infiltrates with irregular, translucent, granular appearing margins. There is associated retinal hemorrhage and inflammatory sheathing, leading eventually to a profound loss of vision. The treatment of choice is ganciclovir, and the lack of enlargement of existing lesions is the indicator of successful maintenance therapy. Since ganciclovir is virustatic rather than virucidal, continuous treatment is required to prevent reactivation. Even with full maintenance therapy, 30-50% of patients experience breakthrough infection. Complications of ganciclovir include conjunctival scarring, scleral induration, and neutropenia. Moreover, ganciclovir cannot be taken concurrently with zidovudine, a drug that promotes the overall well-being and survival status of AIDS patients. The development of new drugs such as foscarnet is expected to eliminate the need for AIDS patients to make a choice between preserving their eyesight and controlling virus replication.
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PMID:AIDS-CMV retinitis: Singapore's first cases. 196 62

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

Intravitreal 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG) has been advocated as an alternative mode of therapy in cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS) because of toxic neutropenia which is a complication of systemic intravenous DHPG. The recommended regimen requires injection of 200 micrograms DHPG intravitreally twice a week for a period of several weeks to months to control the progression of CMV retinitis. A previous study performed to determine the safe dose of intravitreal DHPG was based on a single intravitreal dose study; it does not consider the toxicity which may arise from multiple intravitreal injections of DHPG as it is utilized in the treatment of patients with CMV retinitis. In our study, intravitreal injections of 1000, 400, 200, 100, 50, and 25 micrograms DHPG were administered weekly for a period of 5 weeks in rabbit eyes. Ocular toxicity was monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. Electroretinographic evidence of retinal toxicity was found with doses as low as 100 micrograms. Electron-micrographic studies of retinal tissue from the eyes injected with even lower doses (as low as 25 micrograms) also showed evidence of toxic vacuolization in the inner segments of the photoreceptor.
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PMID:Ocular toxicity of multiple intravitreal DHPG injections. 240 20

Long-term management of cytomegalovirus (CMV) retinitis by intravitreal injection of ganciclovir was evaluated in ten patients with acquired immune deficiency syndrome (AIDS). Patients were unable to tolerate systemic ganciclovir because of severe neutropenia (8 cases), catheter-induced sepsis (1 case), or the need to continue therapy for human immunodeficiency virus (HIV) with zidovudine (ZDV) (1 case). All patients had a favorable response to initial treatment. Cytomegalovirus retinitis progressed in four fellow eyes in which treatment was deferred. Vision improved or remained stable in all but one eye. Patients were followed for a mean of 4 months and received an average of 16.6 intravitreal injections in each eye. Relapse occurred late in the course while on maintenance treatment in five eyes (33%). There was no evidence of toxicity from repeated intravitreal injections. Treatment was very well tolerated. The only severe complication in a total of 249 injections was a single case of Staphylococcus epidermidis endophthalmitis which responded to intravitreal antibiotic treatment. Intravitreal ganciclovir is an effective alternative to systemic ganciclovir in those patients with severe neutropenia and in those patients who desire to remain on systemic ZDV.
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PMID:Treatment of cytomegalovirus retinitis with intravitreal ganciclovir. Long-term results. 254 Apr 70


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