Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytomegalovirus retinitis, the major cause of blindness in patients with the acquired immunodeficiency syndrome, can be arrested by early detection and treatment. We identified 9 screening indices for early CMV retinitis: T-4/T-8 ratio less than 0.11, T-4 count less than 30, T-8 count less than 500, leukocytes less than 4,200, platelets less than 240,000, hemoglobin less than 11.6, hematocrit less than 35, less than 6 for a diagnostic profile which incorporates these 7 indices, and less than 2 for the IA-sum which compounds T-cell inversion and anemia. A threshold value was determined for each index, identified by retrospective review of charts of 15 patients with CMV retinitis and 30 without. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curve area was calculated. The best screening index was the T-cell ratio, which had the highest sensitivity (0.93), negative predictive value (0.94-0.99) and receiver operating characteristic curve area (0.89), and a positive predictive value among the highest (0.50-0.82).
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PMID:Screening indices for cytomegalovirus retinitis in patients with human immunodeficiency virus. 131 Mar 46

The clinical features and results of laboratory investigations of the first 19 Indian patients with AIDS seen in our hospital are presented. Weight loss, fever, and diarrhea were the most common symptoms. Tuberculosis (TB) was the most common secondary infectious disease; among 13 patients, seven had only pulmonary TB, five had pulmonary and extrapulmonary TB, and one had only extrapulmonary TB. Oropharyngeal candidiasis was found in 11 patients. Other secondary infections were predominantly by virulent bacteria. Opportunistic infections other than candidiasis were infrequent; one patient had cryptococcosis, two had symptomatic cryptosporidiosis, one had noncoagulase-positive staphylococcus septicemia, and one had cytomegalovirus retinitis. Reduced lymphocyte counts (particularly of the CD4 subset), anemia, hypoalbuminemia, hyperglobulinemia, and elevated liver enzyme levels were frequent laboratory findings. Six patients are under follow-up, two are lost to follow-up, and 11 have died. Lymphocyte counts less than 500/mm3 were only seen in those patients who subsequently died. Response to antituberculosis therapy was good in several patients. Thus, the clinical profile of Indian patients with AIDS is not different from the common picture of patients of low socioeconomic and poor hygienic standards; patients presented with TB, undernutrition, and multiple infections. Therefore, a large population of patients with AIDS in India will not be recognized unless they are tested for evidence of HIV infection.
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PMID:Clinical and laboratory profile of AIDS in India. 802 23

Foscarnet is an investigational antiviral agent that has been used effectively in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. However, it has not been readily available to AIDS patients with renal insufficiency because its major side effect is nephrotoxicity. In this report, the efficacy, safety, and dosing requirements of foscarnet in a hemodialysis-dependent patient with CMV retinitis are presented. Foscarnet was administered for 14 weeks, at an initial dosage of 60 mg/kg after each dialysis session. Plasma concentrations were monitored weekly, and the dosage was adjusted to maintain peak plasma levels in the range of 500-800 microM. Although some laboratory abnormalities occurred (a preexisting anemia continued, serum calcium and phosphorus decreased, and ionized calcium increased), they did not limit therapy. Foscarnet is a potentially useful alternative treatment for CMV retinitis in hemodialysis-dependent AIDS patients.
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PMID:Successful foscarnet therapy for cytomegalovirus retinitis in an AIDS patient undergoing hemodialysis: rationale for empiric dosing and plasma level monitoring. 165 63

The pyrophosphate analogue, foscarnet, selectively inhibits the DNA polymerase of human herpes viruses, including cytomegalovirus, and the reverse transcriptase of HIV. Viral replication is therefore prevented, but resumes when the drug is cleared from infected cells. In vitro, the combination of foscarnet and zidovudine (azidothymidine) has an additive effect against cytomegalovirus and acts synergistically against HIV. An improvement in cytomegalovirus retinitis is obtained in over 85% of affected AIDS patients during foscarnet induction therapy, but relapse usually occurs within a month of ceasing treatment. There is a similar duration of remission during maintenance therapy given for 5 days each week, but this can be extended 4- to 5-fold with daily administration of higher doses. In allograft recipients, progression of retinitis can be halted by foscarnet until immune function recovers and eradicates the virus. The incidence of acute renal failure, which is common during foscarnet therapy, may be reduced by dosage adjustment and adequate prehydration. Anaemia, phlebitis, nausea and vomiting, and disturbances in serum calcium and phosphate levels, perhaps resulting from uptake of foscarnet into bone or chelation with ionised calcium, have also been associated with administration of the drug. Cytomegalovirus retinitis is difficult to treat, with few therapeutic options available. Although treatment with foscarnet produces some severe adverse effects, with care these can be minimised, and the drug produces clinical improvement in a large proportion of patients; this is a highly encouraging finding at this stage in its development. Preliminary comparative data indicate that foscarnet and ganciclovir are similarly effective, but foscarnet may have some theoretical advantages in AIDS patients since it can be used in combination with zidovudine without potentiating myelosuppression.
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PMID:Foscarnet. A review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. 170 82

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.
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PMID:Foscarnet therapy of cytomegalovirus retinitis in AIDS. 215 35

A total of 314 immunocompromised patients with serious cytomegalovirus (CMV) infection treated with ganciclovir administered intravenously were studied. Rates of favorable clinical response among evaluatable patients were 91 (84%) of 108 for CMV retinitis, 35 (83%) of 42 for gastrointestinal CMV infection, and 26 (72%) of 36 for CMV pneumonia. Of 167 treated patients who had AIDS, improvement or stabilization of CMV disease occurred in 83% as compared with 13% of 39 untreated, historical control patients with AIDS and similar CMV disease (P less than or equal to .004). Virologic response was noted in 111 (92%) of 121 patients who had sequential cultures of blood, urine, or throat washings for CMV. In an attempt to prevent relapse of CMV disease after discontinuation of ganciclovir, maintenance treatment was evaluated in a group of 61 patients with AIDS and CMV retinitis who had received an initial dosage of greater than or equal to 7.5 mg/(kg.d) for greater than or equal to 10 days. Median time to relapse of retinitis was 47 days in patients not receiving maintenance treatment as compared with 105 days in patients treated with 25-35 mg/(kg.w) (P = .0002). Adverse effects of treatment included neutropenia (42%), thrombocytopenia (19%), central nervous system effects (18%), nausea (6%), fever (6%), rash (6%), vomiting, diarrhea, infusion site reactions, and anemia (4% each). It was concluded that ganciclovir has clinical efficacy against CMV disease, as well as an in vivo antiviral effect, and that this agent reduces morbidity of serious CMV infections in immunocompromised patients.
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PMID:Ganciclovir treatment of life- or sight-threatening cytomegalovirus infection: experience in 314 immunocompromised patients. 284 86

The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and the reverse transcriptase of human immunodeficiency virus (HIV) are selectively inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is reversible on withdrawal of foscarnet and additive or synergistic effects have been demonstrated in vitro with other antiviral drugs, including ganciclovir and zidovudine. Foscarnet appears to have negligible effects on host enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more than 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis during foscarnet induction therapy, but relapse occurs soon after ceasing treatment. Maintenance treatment given daily can extend the period of remission considerably. Foscarnet and ganciclovir monotherapy had similar efficacy in the treatment of CMV retinitis in patients with AIDS in several studies, and have been used concomitantly in immunocompromised patients with recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived for significantly longer than those receiving ganciclovir. Foscarnet has been used successfully in the treatment of limited numbers of immunocompromised patients with CMV-associated gastrointestinal (improvement in over 67% of patients) and other infections. Aciclovir-resistant herpes simplex infections in immunocompromised patients have also been treated successfully with foscarnet. Almost 90% of a foscarnet dose is excreted in the urine. Reversible nephrotoxicity is common during foscarnet therapy, but may be reduced by dosage adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in electrolyte levels and genital ulceration have also been associated with administration of the drug. The different tolerability profiles of foscarnet and zidovudine facilitate the use of these agents in combination in patients with AIDS and CMV infection; whereas ganciclovir, like zidovudine, is associated with dose-limiting haematological toxicity. The apparent survival benefits seen in these patients when receiving foscarnet and zidovudine (possibly linked to synergy between zidovudine and foscarnet and/or the inherent anti-HIV activity of foscarnet), appear to offer potentially important advantages for foscarnet over ganciclovir in the treatment of selected patients with AIDS and CMV infections.
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PMID:Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. 752 25

A 41-year-old AIDS patient with fever, nightly perspiration, diarrhoea, anaemia and leukopenia was diagnosed as having visceral leishmaniasis (VL). After 8 weeks of antimony treatment combined with gamma-interferon, given in 2 courses of 3 and 5 weeks, 12 weeks apart, the bone marrow revealed no parasites by microscopy and culture. Parasitic DNA could still be demonstrated by polymerase chain reaction. Weekly intravenous pentamidine maintenance therapy seemed to prevent relapses. Over time the patient was treated for disseminated M. avium infection, CMV retinitis, porphyria cutanea tarda and renal tubular acidosis. Ultimately he succumbed, 2.5 years after the diagnosis of VL and 4.5 years after the diagnosis of AIDS was established.
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PMID:Treatment of visceral leishmaniasis in a patient with AIDS with antimony and gamma-interferon: remission and prevention of relapse by maintenance therapy with weekly pentamidine. 756 84

A 41-year-old man with acquired immunodeficiency syndrome (AIDS) developed cytomegalovirus (CMV) retinitis. Intravenous administration of ganciclovir arrested progression of the retinitis, but it was discontinued due to side effects of severe anemia, neutropenia, and thrombocytopenia. Reactivation of CMV retinitis occurred two weeks after stopping ganciclovir, and then forscarnet was given intravenously. The response was prompt with resolution of the retinitis. There was no progression of retinitis during the treatment. The patient experienced renal dysfunction as a side effect of foscarnet, but it was reversible. As with ganciclovir, foscarnet appeared to be an effective drug for CMV retinitis associated with AIDS. Both drugs have severe adverse events: foscarnet causes renal dysfunction and ganciclovir causes myelosuppression, that necessitated discontinuation of the therapy. We suggest that alternating ganciclovir and foscarnet administration, switching to other treatment on the basis of the clinical response and side effects of the drugs, is an efficacious regimen for the treatment of CMV retinitis associated with AIDS.
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PMID:[Foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome]. 806 6

Ganciclovir is one of only two drugs licensed by the U.S. Food and Drug Administration for the treatment of opportunistic cytomegalovirus (CMV) disease. The combination of ganciclovir and zidovudine has been reported to be poorly tolerated because of dose-limiting hematologic toxicity; thus we retrospectively examined the tolerability of combination therapy with ganciclovir and didanosine in 32 patients with AIDS. These patients were receiving ganciclovir for CMV disease in addition to didanosine in the Videx U.S. Expanded Access Program. During the period of combined therapy, dose-limiting hematologic toxicity (absolute neutrophil count, < 500 cells/microL) developed in only 9.4% of patients and severe anemia (hemoglobin level, < 8.0 g/dL) in only 12.5%. Rates of dose-limiting intolerance to didanosine were similar to those previously reported in the Expanded Access Program. Overall, 15 of 32 patients in the current study tolerated therapeutic doses of didanosine in combination with ganciclovir; in contrast, only 5 of 29 patients tolerated zidovudine (600 mg/d) in combination with ganciclovir in the largest trial of therapy with this combination whose results have been published to date (P = .02, Fisher's exact test). Since recent data suggest that the administration of some form of antiretroviral therapy prolongs survival in patients with CMV retinitis, coadministration of didanosine with ganciclovir should be considered for such patients who do not tolerate other regimens with activity against both retroviruses and CMV.
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PMID:Tolerability of combined ganciclovir and didanosine for the treatment of cytomegalovirus disease associated with AIDS. 838 Oct 32


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