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Biomedical subjects

R B Pollard

Publications and source records attributed to R B Pollard.

At least 127 records · Page 7Linked to original sources

Short-course human leukocyte interferon in treatment of herpes zoster in patients with cancer.

Because of encouraging results when human leukocyte interferon was given for 5 to 7 days to treat early localized herpes zoster in patients with cancer, a small placebo-controlled, randomized, double-blind trial was set up involving only 48 h of therapy. In this trial, there was no effect on acute pain or disease progression in the primary dermatome. However, a modest but significant effect was noted in that distal cutaneous spread was diminished in the treated patients compared with the controls and the treated patients had diminished severity and duration of postherpetic neuralgia. No evidence of impairment in varicella-zoster-specific lymphocyte transformation was observed in interferon-treated patients.

Clinical Trials as Topic↗

Cellular and humoral immunity in the pathogenesis of recurrent herpes viral infections in patients with lymphoma.

86 patients with lymphoma were evaluated prospectively for clinical and laboratory evidence of recurrent varicella-zoster, herpes simplex, and cytomegalovirus infections during the first 16 mo of treatment. Cellular immunity to the viral antigens was measured by in vitro lymphocyte transformation and interferon production. Antibody titers and nonspecific measures of cellular immunity, including T-cell quantitation and transformation to phytohemagglutinin, were also assessed. The patients treated with radiation and chemotherapy had the highest incidence of reactivation of each of the viruses (15-19%). Greater susceptibility to herpes viral reactivation in these patients correlated with suppression of cell-mediated immunity to the specific virus. In individual patients, suppression of cellular immunity to the specific herpes viral antigen preceded each episode of reactivation, but recurrent infection did not occur in all patients with diminished specific lymphocyte transformation. Absence of the response appears to be a necessary but not a sufficient condition for the recrudescence of latent infection. Better preservation of cellular immunity to herpes simplex antigen during treatment was associated with infrequent reactivation of herpes simplex. In 25 patients with acute herpes zoster, uncomplicated recovery from the infection was accompanied by the development of lymphocyte transformation and interferon production to varicella-zoster antigen. Quantitation of T-cell numbers and phytohemagglutinin transformation did not correlate with the presence of viral cellular immunity in treated patients. Responses returned while T-cell numbers were low, and the recovery of phytohemagglutinin transformation often preceded recovery of the responses to viral antigens. Although some patients had deficiencies in viral cellular immunity at diagnosis, the duration of the suppression of specific antiviral responses resulting from treatment appears to be the most important factor predisposing to the recurrence of herpes infections in lymphoma patients.

Antibody Formation↗

Cytomegalovirus retinitis in immunosuppressed hosts. I. Natural history and effects of treatment with adenine arabinoside.

Cytomegalovirus (CMV) retinitis presents with typical ophthalmologic appearance in patients with underlying immunosuppressive conditions. Fourteen patients with this disorder were diagnosed by culture of cytomegalovirus from urine or throat specimens, elevated complement fixation titers to cytomegalovirus, and characteristic funduscopic appearance. Ten of 11 had decreased CMV-specific cell-mediated immune responses. Three of seven who received no specific therapy improved after decreasing dosages of immunosuppressive drugs. Seven patients with progressive disease despite minimal immunosuppressive therapy were treated with adenine arabinoside at doses from 1 to 20 mg/kg of body weight per day. Daily dosages of 20 mg/kg . d in five patients were associated with decreased inflammatory activity and improvement of retinal lesions and quantitative decreases in urinary virus excretion. Adenine arabinoside administration was associated with significant gastrointestinal, hematologic, and neurologic side effects. Adenine arabinoside may have some beneficial effect on selected patients with progressive CMV retinitis.

Adult↗

Cytomegalovirus retinitis in immunosuppressed hosts. II. Ocular manifestations.

We observed the course of cytomegalovirus (CMV) retinitis in 21 eyes of 14 immunosuppressed patients. In two patients, other organisms, specifically Toxoplasma and Candida, also appeared to be causing retinal disease simultaneously. Post-mortem examination was done on 10 eyes from seven patients. At initial presentation, the retinitis was often asymptomatic and diagnosed during routine examination. The ophthalmoscopic picture was characteristic of cytomegalovirus; the early lesion was a small opaque, white granular area of retinal necrosis that spread in a centrifugal, brush-fire-like manner over 1 to 8 months. Vessel sheating and hemorrhages appeared as the disease progressed. In two patients new foci of retinitis developed remote from the original lesion. Four weeks to 4 months (average, 10 weeks) elapsed from the most extensive disease to total resolution. Resolution of active disease left a subtle retinal scar, and final visual acuity was reduced in one half the eyes. Repeated ophthalmoscopic examinations can aid in early diagnosis of CMV retinitis and in ascertaining which persons are most at risk for visual loss.

Candidiasis↗

Effects of interferon and adenine arabinoside treatment of hepatitis B virus infection on cellular immune responses.

Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10(5) U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10(5) U of HLI per kg per day. Antiviral therapy with <10(5) U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 mug/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.

Acute Disease↗

Human leukocyte interferon for the treatment of herpes zoster in patients with cancer.

We tested the effect of human leukocyte interferon on early localized herpes zoster infections in three placebo-controlled, randomized double-blind trials involving 90 patients with cancer. There were no significant differences in pretreatment severity of infection or nature of underlying disease in the groups. Higher dosages of more purified interferon in the second and third trials produced a significant (P less than or equal to 0.01) decrease in cutaneous dissemination. No dissemination occurred in those receiving the highest dosage (5.1 x 10(5) U per kilogram per day) (P less than or equal to 0.025). The number of days of new-vesicle formation in the primary dermatome decreased (mean, 2.3 days, P less than or equal to 0.05) in this group. Treated patients had a trend toward less acute pain, and significantly (P less than or equal to 0.05) diminished severity of post-herpetic neuralgia, at the two highest dosage levels. Visceral complications were six times less frequent in interferon recipients. High-dosage interferon appeared effective in limiting cutaneous dissemination, visceral complications and progression within the primary dermatome.

Blood Cell Count↗

Selective impairment of lymphocyte reactivity to varicella-zoster virus antigen among untreated patients with lymphoma.

Herpes zoster is a frequent complication of lymphoreticular malignancy. In this study two assays of in vitro cellular immune response to varicella-zoster virus (VZV) antigen, lymphocyte transformation and interferon production, were performed in normal subjects with recent and remote VZV infection. The responses of patients with lymphoma were measured before treatment and during long-term remission and then compared with those of normal subjects. Despite levels of antibody to VZV that were equivalent to those in normal subjects, 44% of the untreated lymphoma patients showed a lower transformation response to VZV antigen than the normal patients. Production of interferon in response to VZV antigen was absent in 32% of the untreated patients. In contrast, lymphocyte responses in untreated patients to herpes simplex virus antigen were within the range observed in a normal population. Interferon production by lymphocytes in response to cytomegalovirus antigen was also lower among untreated lymphoma patients than among normal patients, but lymphocyte transformation was not. Twenty-two percent of lymphoma patients in long-term remission continued to have diminished cellular immune responses to VZV antigen. Observations in these patient populations and in normal subjects with acute herpes zoster suggest that deficiencies in in vitro lymphocyte responses may correlate with increased susceptibility to clinical infection with VZV.

Antibodies, Viral↗

Cell-mediated immunity of cytomegalovirus infection in normal subjects and cardiac transplant patients.

Two assays of cell-mediated immunity, lymphocyte transformation and interferon production, were adapted to test for specific immunity to cytomegalovirus (CMV). Normal individuals seropositive for CMV had a mean transformation index of 7.9 in response to antigen of the Davis strain of CMV, whereas all of 14 seronegative normal individuals had transformation indexes of less than or equal to 3.0. Interferon production in seropositive and seronegative individuals was not statistically different. One to two months after CMV mononucleosis (after the termination of viruria), normal individuals had increased transformation indexes. Recipients of cardiac transplants within six months after transplant had normal levels of antibody to CMV; lymphocyte transformation and interferon production in these subjects were markedly decreased and returned to normal by three years and between one and three years after transplant, respectively. A syndrome of unexplained fever, hepatitis, pneumonitis, leukopenia, and atypical lymphocytes was common in a group of recipients with primary CMV infection. Shedding of virus was frequent in these symptomatic patients and in patients with repeat infection during the first three years after transplant. These assays appear to identify periods of immune deficits correlating with increased incidence of infection with CMV.

Cytomegalovirus Infections↗

Lymphocyte transformation and interferon production as measures of cellular immunity in lymphoma patients.

Our studies of in vitro cellular immune responses to herpesviruses have shown that, before treatment, lymphoma patients have decreased transformation to varicella-zoster virus antigen compared to herpes simplex virus and cytomegalovirus antigens. Interferon production to varicella-zoster virus and cytomegalovirus antigens is also decreased. During the first six months of treatment, decreased lymphocyte transformation and interferon production to all herpesviral antigens was observed. Among patients in long-term remission, recovery from the suppression associated with treatment was noted except that interferon production to varicella-zoster virus antigen remained decreased.

Antigens, Viral↗

Cellular immunity and herpesvirus infections in cardiac-transplant patients.

We observed severe infection with herpes simplex virus in cardiac-transplant patients despite their high serum antibody levels to this virus. Therefore, we sought to correlate clinical susceptibility to two herpesvirus (simplex and zoster) infections with specific cellular immunity, assessed by the transformation and interferon responses of peripheral blood mononuclear cells to heat-inactivated antigens. Transformation and interferon response to herps simplex virus was maximally depressed immediately after transplantation, the time when severe and prolonged infection with herps simplex virus occurred. Six months to six years after transplantation, both clinical susceptibility and cellular immunity to herpes simplex virus were normal. Herpes zoster infections were more frequent than normal at all times after cardiac transplantation; depressed or absent cellular responses to the varicella zoster virus paralleled that susceptibility. In these patients the risk of severe herpesvirus infections correlated with depressed cellular immune responses to the specific viral agent involved.

Antibodies, Viral↗

Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis.

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.

Adult↗