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Biomedical subjects

M A Jacobson

Publications and source records attributed to M A Jacobson.

At least 127 records · Page 7Linked to original sources
PubMed1989

Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized (no new retinal lesions and stable old lesions [7 patients]) or improved (decreased retinal opacification [2 patients]). All eight patients with CMV in urine or blood upon entry into the study had negative urine and blood cultures at the end of induction. After induction therapy, seven patients continued maintenance foscarnet therapy, 60 mg/kg as a single daily infusion, 5 days/week. In six patients, retinal lesions increased in size after 2 to 32 weeks of maintenance therapy. One was invaluable because a retinal detachment developed. Only 9 of 42 blood and urine cultures obtained during maintenance foscarnet therapy yielded CMV, compared with 7 of 14 obtained prior to the initiation of foscarnet induction therapy (P = 0.04). Foscarnet toxicity was mild and infrequent: elevation in serum creatinine by 0.5 to 1.3 mg/dl over the base line (two patients), muscle twitching (three patients), hemoglobin decrease by 1 mg/dl (two patients), nausea (two patients), absolute neutrophil count decrease by 50% (one patient), rise in serum phosphorus to greater than 5.5 mg/dl (four patients), and proteinuria (two patients). Intermittently administered intravenous foscarnet appears to be an effective, relatively nontoxic therapy for CMV retinitis. Additional studies to determine the optimal dosage for maintenance therapy are needed, as are comparative trials with ganciclovir.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Pharmacokinetics of intermittently administered intravenous foscarnet in the treatment of acquired immunodeficiency syndrome patients with serious cytomegalovirus retinitis.

Foscarnet has been shown to be active in vitro against the human immunodeficiency virus and all human herpesviruses including cytomegalovirus (CMV). A pharmacokinetic study was carried out as part of a clinical trial designed to evaluate the safety and efficacy of intermittently administered intravenous foscarnet for the treatment of CMV retinitis. Eight patients with acquired immunodeficiency syndrome and serious CMV retinitis received 2-h intravenous infusions of foscarnet at a dosage of 60 mg/kg of body weight every 8 h for 14 days. Serial plasma samples were collected on days 3 and 14 of therapy, and foscarnet concentrations were determined by high-pressure liquid chromatography. On day 3 of therapy, the mean (+/- standard deviation) peak and trough levels in plasma were 509 (200) and 98 (29) microM, respectively, while on day 14 levels were 495 (149) and 126 (59) microM. The mean clearance in plasma on days 3 and 14 were 1.9 (0.6) and 1.7 (0.9) ml/min per kg, respectively. On day 14, the mean half-life was 4.5 (1.2) h and the volume of distribution was 0.74 (0.60) liter/kg. As the half-life and the clearance of foscarnet in plasma correlated with changes in renal function, dosage adjustments must be made for patients with decreased renal function.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Zidovudine-induced fever.

Zidovudine (3'-azido-3'deoxythymidine, AZT, Retrovir) is the first antiretroviral drug to demonstrate clinical efficacy for symptomatic human immunodeficiency virus infection. In a large, placebo-controlled trial, nausea and hematologic toxicity, but not fever, occurred more frequently in zidovudine- than in placebo-treated patients. However, in an open label study, fever severe enough to halt zidovudine administration occurred in 10% of 70 acquired immune deficiency syndrome (AIDS) patients receiving the drug. We now describe three AIDS patients with severe zidovudine-induced fever in whom other causes of fever were excluded. Zidovudine-induced fever was confirmed in each case by drug rechallenge. Using an enzyme immunoassay, we detected IgM antibodies directed against a zidovudine-serum protein conformational determinant in one of these three patients. Neither IgG nor IgM anti-zidovudine antibodies were present in sera from the other two patients with zidovudine fever, from four AIDS patients who discontinued zidovudine for reasons other than fever, or from five AIDS patients who never received zidovudine. Zidovudine may cause fever as a severe adverse effect in patients with AIDS. Either type III or type IV hypersensitivity may mediate this reaction.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Failure of antiviral therapy for acquired immunodeficiency syndrome-related cytomegalovirus myelitis.

We report the first published case (to our knowledge) of histopathologically documented acquired immunodeficiency syndrome-related cytomegalovirus (CMV) myelitis in which antiviral drug therapy was administered. Despite sensitivity of the patient's CMV isolate to therapy with both ganciclovir and foscarnet, use of neither of these agents halted progression of central nervous system CMV disease. Higher doses of these drugs or combination therapy may be required to treat acquired immunodeficiency syndrome-related CMV myelitis effectively.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Randomized prospective trial of ganciclovir maintenance therapy for cytomegalovirus retinitis.

We report the first randomized prospective comparative study of long-term maintenance ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine, BW759U, DHPG) therapy for cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Eleven retinitis patients who received a 10-day course of ganciclovir induction therapy and then were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (eight deferred maintenance, three immediate maintenance) were evaluated for drug efficacy. Median time to retinitis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (P = 0.07). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (P = 0.13). Only 9% of cultures obtained while patients received maintenance therapy were positive for cytomegalovirus, vs 40% of those obtained off maintenance (P less than 0.001). We can state then that maintenance therapy with ganciclovir delays, but does not halt, progression of cytomegalovirus retinitis and suppresses, but does not eradicate, cytomegalovirus shedding in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cholestasis and disseminated cytomegalovirus disease in patients with the acquired immunodeficiency syndrome.

A cholestatic syndrome caused by papillary stenosis and sclerosing cholangitis (PS/SC) has been recently described as a complication of the acquired immunodeficiency syndrome (AIDS). Cytomegalovirus has been implicated as an etiologic factor in this syndrome. Consecutive cases of disseminated cytomegalovirus disease and viremia were reviewed for evidence of cholestasis. In 12 of 36 (33 percent) patients with cytomegalovirus infection (gastrointestinal disease [eight of 16 patients] or retinitis [four of 20 patients]), cholestatic liver enzyme abnormalities developed within three months of the diagnosis of cytomegalovirus disease. Radiologic imaging demonstrated biliary dilation in three of nine (33 percent) patients studied. Review of serial liver function tests showed no effect of ganciclovir therapy on the course of cholestatic abnormalities. AIDS patients without CMV end-organ disease were also reviewed for evidence of cholestasis. Six of 15 AIDS patients with positive blood culture results for cytomegalovirus had cholestatic liver enzyme abnormalities compared with four of 36 AIDS patients with negative viral blood culture results (p = 0.023, Fisher's exact test). Patients with cytomegalovirus retinitis, gastrointestinal disease, or viremia appear to be at increased risk for the development of cholestasis. In 3 to 11 percent of patients with cytomegalovirus retinitis or gastrointestinal disease, PS/SC may develop. This clinical association supports an etiologic role for cytomegalovirus in the PS/SC syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Staphylococcus aureus bacteremia and recurrent staphylococcal infection in patients with acquired immunodeficiency syndrome and AIDS-related complex.

PURPOSE: An increased incidence of Staphylococcus aureus bacteremia has recently been described in patients with the acquired immunodeficiency syndrome (AIDS). However, other risk factors for community-acquired S. aureus bacteremia (including intravenous drug abuse and lymphedema) were present in nearly all these AIDS-related cases of S. aureus infection. Our purpose was to review cases of S. aureus bacteremia that occurred in patients with AIDS or AIDS-related complex (ARC) who did not have a recent history of intravenous drug use, lymphatic obstruction, or neutropenia. PATIENTS AND METHODS: Patients at San Francisco General Hospital between October 1984 and October 1987 with blood culture results positive for S. aureus were identified. A review of this group revealed 22 cases of S. aureus bacteremia that occurred in 18 patients with an underlying diagnosis of AIDS or ARC, none of whom had a recent history of intravenous drug use, lymphedema secondary to Kaposi's sarcoma, or neutropenia. RESULTS: An intravenous catheter was the single most important risk factor for S. aureus bacteremia and was identified as the source for bacteremia in 16 (73 percent) of the 22 episodes. Based on 1986 outpatient clinic records, we calculated an incidence of S. aureus bacteremia occurring in non-intravenous-drug-using male AIDS or ARC patients, 18 to 44 years old, that was 5.4 episodes/1,000 patients. Although the mean duration of appropriate antibiotic therapy was 18 days, late metastatic complications of S. aureus bacteremia occurred in six (35 percent) of 17 AIDS/ARC patients who survived initial antibiotic therapy. CONCLUSION: Non-intravenous-drug-using AIDS and ARC patients (especially those with indwelling venous catheters) appear to be at high risk for S. aureus bacteremia, with a higher late metastatic complication rate than that reported for recent historical control subjects.

AIDS-Related Complex↗
PubMed1988

Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment.

Life-threatening opportunistic cytomegalovirus infection is a complication of the acquired immunodeficiency syndrome (AIDS) that occurs in 7.4% or more of patients with AIDS. Cytomegalovirus retinitis, colitis, esophagitis, and gastritis are the commonest manifestations of severe cytomegalovirus end-organ disease. Extensive trials with intravenous ganciclovir, a nucleoside analogue with myelosuppressive toxicity, have shown that ganciclovir halts the progression of cytomegalovirus retinitis and gastrointestinal disease. Since relapse is common when therapy is discontinued, most patients with AIDS need life-long maintenance therapy. The clinical response to ganciclovir therapy is usually accompanied by diminished shedding of the virus. Based on limited data, foscarnet, a pyrophosphate analogue, also appears to have some efficacy in treating cytomegalovirus infection. Unlike ganciclovir, foscarnet does not cause myelosuppression. An important direction for future clinical research is the development of more effective and less toxic therapy, as well as orally bioavailable drugs for maintenance therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cytomegalovirus infection.

The pathogenic importance of cytomegalovirus (CMV) infection in AIDS-associated pneumonitis is controversial. Uncertainty regarding the significance of CMV isolation from pulmonary secretions of AIDS patients results in part from the difficulty in distinguishing CMV infection from CMV disease and from the high frequency of pulmonary CMV co-infection with other opportunistic pathogens. From our review of the literature to date, we have found only three cases in which AIDS patients with hypoxemia and infiltrates on chest x-ray had lung biopsy or autopsy material reported to demonstrate CMV cytopathic effect in the absence of any other pathogen. However, pulmonary CMV co-infection may be a marker of poor outcome in Pneumocystis carinii pneumonia. In this article, appropriate criteria for instituting specific therapy with the antiviral drug ganciclovir are described.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Retinal and gastrointestinal disease due to cytomegalovirus in patients with the acquired immune deficiency syndrome: prevalence, natural history, and response to ganciclovir therapy.

Of 760 AIDS patients seen at San Francisco General Hospital in 1986, 5.7 per cent had retinitis and 2.2 per cent had gastrointestinal disease caused by cytomegalovirus. We reviewed the records of 44 patients treated with ganciclovir for culture-confirmed cytomegalovirus retinal (31 patients) or gastrointestinal disease (17 patients) or both (four patients) in 1986. Retinitis stabilized or improved during initial treatment with ganciclovir in 22 of 27 (81.5 per cent) patients. Following a median 10-day induction course, 16 patients with retinitis continued to have serial ophthalmologic assessments: eight patients were maintained on treatment and eight had maintenance treatment deferred. Before treatment, the two groups were comparable in age, Karnofsky scores, hematologic assessment, visual acuity, and history with respect to Pneumocystis carinii pneumonia. Retinitis did not progress for a median 53.8 days in the immediate maintenance group compared to 18.8 days for the deferred maintenance group (p = 0.01). In 17 patients with CMV gastrointestinal disease, nine of 14 (64 per cent) had resolution of pain and eight of 11 (73 per cent) had resolution of diarrhea when treated initially with ganciclovir. In both retinitis and gastrointestinal disease patients, ganciclovir decreased recovery of CMV from urine and blood markedly. Ganciclovir also caused a decrease in mean absolute neutrophil counts to about half of baseline values; decreases in mean platelet count and hemoglobin were also noted but were less than 25 per cent. Neutropenia severe enough to require dose adjustment (less than 800 cells/microliters) occurred in 31 per cent of patients receiving maintenance ganciclovir.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mycobacterial diseases. Tuberculosis and Mycobacterium avium complex.

Pulmonary or extrapulmonary tuberculosis occurs in 5 to 35 per cent of AIDS patients, frequently precedes the diagnosis of AIDS, and is increasing in incidence. Clinically, AIDS-associated tuberculosis is similar in presentation to progressive, primary tuberculosis and can be treated effectively with standard antituberculous therapy. Disseminated Mycobacterium avium complex (MAC) infection, one of the most common AIDS-related opportunistic infections, is best diagnosed by special mycobacterial blood culture techniques. The relationship between MAC infection and constitutional symptoms as well as the value of antimycobacterial therapy for disseminated MAC is controversial.

AIDS-Related Complex↗
PubMed1988

Projecting the medical costs of AIDS and ARC in the United States.

We projected the direct medical costs of acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) for the United States during the period 1987-1991, by applying current epidemiologic projections to state-of-the-art medical decision algorithms for diagnosis and treatment of AIDS-related illnesses. We included the cost of azidothymidine (AZT) therapy, as well as other therapeutic innovations likely to be approved by the FDA, and estimated average ARC patient treatment costs. By combining prospective study data on rates of progression to AIDS with current AIDS incidence data, we arrived at human immunodeficiency virus (HIV) seroprevalence and AIDS incidence projection that were considerably lower than those of the Public Health Service. We estimated the average total medical costs per patient for AIDS in the 1990s at $27,950-$40,455 and for ARC at $3,621-$4,913 per year (1987 U.S. dollars). We projected the medical costs of AIDS and ARC at $2-4 billion annually by 1991, substantially lower than previous estimates. We projected that Pneumocystis carinii pneumonia and other pulmonary complications would account for the largest share (over 40%) of AIDS medical costs, and that AZT therapy and medication would account for more than 25% of total ARC/AIDS treatment costs by 1991. In our estimates, the total medical costs of treating ARC patients could approach one-half of the costs of treating AIDS patients by 1991, primarily due to costs associated with AZT.

AIDS-Related Complex↗
PubMed1987

Human pharmacokinetics and tolerance of oral ganciclovir.

Ganciclovir is a nucleoside analog which inhibits the replication of herpesviruses in vitro and which has been effective by intravenous administration for the treatment of severe cytomegalovirus infection in immunocompromised patients. Because most patients with acquired immunodeficiency syndrome and severe cytomegalovirus infection have required lifelong daily suppressive ganciclovir therapy to control disease progression, oral therapy appears to have practical advantages. We studied the pharmacokinetics of orally administered ganciclovir in four patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. Repeated oral ganciclovir doses (10 to 20 mg/kg every 6 h) were well tolerated. With a 20-mg/kg dose given every 6 h, mean steady-state peak and trough levels were 2.96 and 1.05 microM, respectively, and the area under the concentration-time curve from 0 to 24 h was 47 microM X h. Calculated absorption was 3.0%, based on urinary excretion. Because the levels achieved in serum with oral ganciclovir approximated those required to inhibit cytomegalovirus in vitro, a trial of oral maintenance therapy in immunocompromised patients with severe cytomegalovirus infections seems warranted.

Acquired Immunodeficiency Syndrome↗