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Biomedical subjects

D H Shepp

Publications and source records attributed to D H Shepp.

At least 37 records · Page 2Linked to original sources
PubMed1992

Herpes simplex virus infection in cancer patients: prevention and treatment.

Herpes simplex virus (HSV) infection is common in patients receiving cytotoxic therapy for cancer. Almost all infections result from reactivation of latent virus during treatment-induced immunosuppression. Typical, self-limited orolabial or genital ulceration does not always require laboratory diagnosis or treatment, but HSV may present in an atypical fashion in cancer patients and cause more severe and prolonged mucocutaneous infection or visceral disease. The presence of antibodies to HSV identifies patients at risk for recurrent HSV infection. The treatment of choice is acyclovir, which may also be used to prevent infection in high-risk patients. Acyclovir resistance has been reported in patients with profound and prolonged immune deficiency, but remains rare in patients treated for cancer.

Acyclovir↗
PubMed1990

Acyclovir-resistant herpes simplex virus causing pneumonia after marrow transplantation.

Three marrow transplant patients developed pneumonia due to acyclovir-resistant thymidine-kinase-deficient herpes simplex virus (HSV) type 1. In all three, pneumonia was evident at autopsy by both standard and immunohistology, and virus was recovered from culture of lung tissue. Two patients also had other pulmonary infections at death; one had only HSV pneumonia. All had received prophylaxis and repeated treatment courses with acyclovir, and all initially had acyclovir-sensitive virus. The acyclovir-resistant HSV strains were sensitive to foscarnet, and in at least one case to vidarabine, but as expected were resistant to ganciclovir. These cases represent potentially severe visceral infection in which acyclovir-resistant virus strains were primary or important copathogens. Although acyclovir-resistant HSV is generally considered less virulent, these cases illustrate the potential importance of infection due to acyclovir-resistant HSV in severely immunocompromised patients. They also highlight the need to test HSV strains for antiviral sensitivity and to consider alternative therapies to acyclovir in appropriate clinical situations.

Acyclovir↗
PubMed1988

Current therapy of varicella zoster virus infection in immunocompromised patients. A comparison of acyclovir and vidarabine.

Both acyclovir and vidarabine are effective treatment for varicella zoster virus (VZV) infection in immunosuppressed patients. To determine which is preferable, therapy with these two agents was compared in a prospective, randomized trial. A total of 22 immunocompromised patients undergoing treatment for hematologic malignancies and presenting with VZV infection within 72 hours of the onset of rash were randomly assigned to receive intravenous acyclovir or vidarabine; 11 patients were randomly assigned to each treatment group. Acyclovir was significantly more effective than vidarabine in preventing complications of VZV infection, and treatment failures requiring a change to the alternate therapy occurred only among those treated with vidarabine. As compared with vidarabine, acyclovir shortened the median period during which results of viral culture specimens were positive and new lesions formed. Acyclovir also shortened the median interval until the first decrease in pain, the crusting of all lesions, and the complete healing of lesions. Acyclovir is more effective than vidarabine in the treatment of VZV infection in severely immunocompromised patients and should be considered the treatment of choice in such cases.

Acyclovir↗
PubMed1988

Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation.

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.

Acyclovir↗
PubMed1988

Human class I MHC-restricted cytotoxic T-lymphocytes specific for human immunodeficiency virus envelope antigens.

Vaccines incorporating HIV envelope antigens are being developed for the prevention of AIDS. To determine whether HIV envelope antigens are recognized by human cytotoxic T-lymphocytes (CTL), we assessed class I MHC-restricted, HIV envelope antigen-specific cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals, following in vitro stimulation. The target cells were human skin fibroblasts of known tissue type, infected with recombinant vaccinia viruses, either containing or lacking the whole HIV envelope gene. Ten out of 17 (59%) asymptomatic HIV-seropositive individuals demonstrated HIV envelope antigen-specific cytotoxicity at levels that were above those seen in HIV-seronegative controls. MHC restriction of cytotoxicity was evident in that 13 out of 19 (68%) of the targets matched for the tissue type of the donor at one or more class I MHC loci were lysed, but only two out of 18 (11%) mismatched targets (P = 0.0004). Both partial purification of effector cells and evidence of MHC restriction indicated that T-lymphocytes were responsible for the observed cytotoxicity. HIV envelope antigen-specific CTL can be detected following in vitro stimulation of the PBMC in many asymptomatic HIV-seropositive individuals. HIV envelope antigens are recognized by human CTL and are, therefore, potentially relevant immunogens for induction of HIV-specific CTL responses.

Antigens, Viral↗
PubMed1988

Ganciclovir treatment of cytomegalovirus infection of the gastrointestinal tract after marrow transplantation.

Ganciclovir, an acyclic nucleoside with improved activity against cytomegalovirus in vitro, was used to treat 15 marrow transplant patients with symptomatic cytomegalovirus infection of the gastrointestinal tract. Eleven of the 15 had improvement in one or more of their clinical signs or symptoms during treatment. No clinical relapses were observed. Viral excretion from throat, urine and blood stopped at a median of 6 days of treatment, but six patients had recurrence of viral excretion 7-25 days after treatment was stopped. The only toxicity was the development of reversible neutropenia in eight of 15 patients after 10-19 days of treatment. Neutropenia was not related to duration of treatment, plasma drug levels or to the neutrophil count at the beginning of treatment. Although treatment with ganciclovir may be associated with marrow suppression, the serious nature of gastrointestinal infection due to cytomegalovirus in the immunocompromised host, the antiviral effect and the possible clinical improvement observed in vivo, and the lack of other effective treatments justify further controlled studies with this agent in immunocompromised patients with serious cytomegalovirus infection.

Acyclovir↗
PubMed1987

Sequential intravenous and twice-daily oral acyclovir for extended prophylaxis of herpes simplex virus infection in marrow transplant patients.

To define an effective and convenient means for providing extended prophylaxis of herpes simplex virus (HSV) infection to chronically immunocompromised patients, we studied a two-part regimen of intravenous, followed by oral, acyclovir after marrow transplantation. Seropositive patients were first given intravenous acyclovir until day 30 after transplant. Intravenous acyclovir (250 mgm/m2) given twice daily to 34 patients during this period was 90% virologically effective among those completing the prophylactic course. A randomized, double-blind comparison of twice-daily oral acyclovir (800 mg) and placebo was then conducted from day 31 to day 75 after transplant in 51 patients. Oral acyclovir significantly delayed the median time to first excretion of HSV when compared with placebo (greater than 100 vs. 70 days after transplant, P = 0.0006) and was completely effective in all patients for the duration of drug administration. Patients receiving extended prophylaxis appeared to have less-severe HSV infection when later recurrences did occur. Sequential intravenous and oral acyclovir given twice daily is an effective and convenient regimen for extended prophylaxis of HSV infection following marrow transplantation, and should be useful in other transplant patients or other chronically immunosuppressed patients as well.

Acyclovir↗
PubMed1986

Treatment of varicella-zoster virus infection in severely immunocompromised patients. A randomized comparison of acyclovir and vidarabine.

In a prospective, randomized trial, we compared intravenous acyclovir and vidarabine in the treatment of varicella-zoster virus infection in severely immunocompromised patients who presented within 72 hours of onset of the infection. Eleven patients were treated in each group. Cutaneous dissemination of infection occurred in none of the 10 acyclovir recipients and in 5 of the 10 vidarabine recipients who had presented with localized dermatomal disease (P = 0.016). As compared with vidarabine, acyclovir treatment shortened the median periods during which cultures were positive for the virus (four vs. seven days, P = 0.004) and new lesions formed (three vs. six days, P = 0.03). Acyclovir also shortened the median interval until the first decrease in pain (4 vs. 7 days, P = 0.005), the pustulation of all lesions (4 vs. 7 days, P = 0.0004), the crusting of all lesions (7 vs. 17 days, P = 0.0003), and the complete healing of lesions (17 vs. 28 days, P = 0.003). In addition, acyclovir reduced the incidence of fever (two vs. eight patients, P = 0.015). We conclude that acyclovir is better than vidarabine for the treatment of varicella-zoster infection in immunocompromised patients.

Acyclovir↗
PubMed1985

Comparative trial of ketoconazole and nystatin for prevention of fungal infection in neutropenic patients treated in a protective environment.

In a randomized trial we compared ketoconazole (400 mg once daily, 27 patients) and nystatin (3 X 10(6) units four times daily, 29 patients) for prevention of fungal infection in neutropenic patients undergoing marrow transplantation in a protective environment. Fewer weekly surveillance cultures contained Candida species in ketoconazole recipients than in nystatin recipients (70 [26%] of 274 vs. 151 [47%] of 322; P less than .001). When all fungi were considered, the difference in colonization was less but was still significant (117 [43%] of 274 vs. 173 [54%] of 322; P = .01), primarily due to increased colonization of the rectum with Torulopsis glabrata among ketoconazole recipients (P less than .001). No difference in the incidence of local mucosal infection was seen. Two disseminated fungal infections occurred, both in nystatin recipients. Compliance with ketoconazole was significantly better than was compliance with nystatin (96% vs. 68%; P less than .001), but similar effects on colonization were found in an analysis adjusting for compliance. Ketoconazole was better tolerated and more effective than nystatin in reducing colonization due to Candida species but was also associated with significantly increased rates of colonization with T. glabrata.

Agranulocytosis↗
PubMed1985

Once-daily intravenous acyclovir for prophylaxis of herpes simplex virus reactivation after marrow transplantation.

To determine the most convenient and least expensive regimen for prevention of recurrent herpes simplex virus (HSV) infection after marrow transplantation, we conducted a randomized, double-blind comparison of intravenous acyclovir 250 mg/m2 and placebo given once daily for four weeks. Six of 14 acyclovir and nine of 13 placebo recipients shed HSV during prophylaxis. All nine culture-positive placebo recipients developed associated lesions during prophylaxis compared to four of six acyclovir recipients. Median time to first culture-positive lesion was significantly delayed by acyclovir compared to placebo (33 days after transplant vs. 10; P = 0.05). Acyclovir-resistant HSV was recovered from one acyclovir recipient while receiving prophylactic acyclovir, and from two placebo recipients during subsequent administration of therapeutic acyclovir. Once-daily intravenous acyclovir can significantly delay time to appearance of culture-positive HSV lesions after marrow transplant, but virological and clinical breakthrough may occur and optimal prevention will require administration of intravenous acyclovir more than once daily.

Acyclovir↗
PubMed1985

Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients.

In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.

Acyclovir↗
PubMed1985

Toxoplasma gondii reactivation identified by detection of parasitemia in tissue culture.

Three patients developed acute toxoplasmosis after allogeneic marrow transplantation for treatment of leukemia. In each case, Toxoplasma gondii was isolated from peripheral blood buffy-coat cells inoculated into fibroblast tissue culture after 10 to 39 days of incubation. Serologic studies did not suggest acute toxoplasmosis, but complete autopsies done in two patients showed active invasive disease. Serologic tests done before the transplants showed that these cases resulted from reactivation of latent infection rather than primary disease. Parasitemia is a feature of reactivation toxoplasmosis in immunosuppressed patients that may be identified by recovery of T. gondii from peripheral blood buffy-coat cells in tissue culture.

Adult↗
PubMed1985

Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia.

Ten marrow transplant recipients with biopsy-proven cytomegalovirus pneumonia were treated with the acyclic nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (BW B759U). Viruria and viremia ceased after 4 days of treatment in all patients with cultures initially positive from these sites. Cytomegalovirus was eliminated from respiratory secretions after a median of 8 days. Despite this antiviral effect, only one patient survived the pneumonia. Quantitative cultures of lung tissue before and after treatment confirmed that therapy with BW B759U was associated with substantial antiviral activity, with a mean decrease in viral titers of more than 99.99% after treatment. Neutropenia developed in three patients when mean peak and trough plasma levels exceeded 50 and 10 mu mol/L, respectively, but no other toxicity was seen. BW B759U is the first antiviral agent showing consistent activity against cytomegalovirus in vivo, and it should be evaluated in the earlier management of cytomegalovirus infections after marrow transplantation and in serious cytomegalovirus infections in other immunocompromised patients.

Acyclovir↗
PubMed1984

Acyclovir treatment of varicella-zoster virus infection in the compromised host.

Forty marrow transplant patients were treated with acyclovir for varicella-zoster virus infection. Median duration of virus positivity and of new lesion formation was 2.1 and 2.2 days, and pustulation , crusting, and healing occurred at medians of 3.5, 8, and 28 days, respectively. Acute pain ceased at a median of 7 days, though seven patients had later recurrence of pain and eight had pain that persisted for more than 28 days. Three patients had recurrence of infection within 4 days after the end of treatment and were successfully treated in each case with a second course of acyclovir. Side effects were minimal. These data compare favorably with published data both from the treatment of normal persons with acyclovir and treatment of normal persons with acyclovir and treatment of immunocompromised patients with vidarabine, and they indicate that acyclovir is safe and effective for the treatment of varicella-zoster virus infection in the severely immunocompromised host.

Acyclovir↗