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Biomedical subjects

J F Rooney

Publications and source records attributed to J F Rooney.

At least 19 recordsLinked to original sources
PubMed2001

Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection.

Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found. Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue. These procedures are often painful and are characterized by a high relapse rate. We report here what is to our knowledge the first double-blind, placebo-controlled study of the use of cidofovir, a nucleotide analogue, for the treatment of genital papillomavirus infections. Thirty patients were enrolled in the study; 19 received cidofovir, and 11 received placebo. The median number of warts and the median baseline wart area were comparable for both groups. Nine (47%) of 19 patients in the cidofovir group had a complete response (total healing), compared with 0 of the patients in the placebo group (P=.006). None of the patients in the cidofovir group experienced progression of the disease, compared with 5 (45%) of 11 patients in the placebo group. The side effects recorded for both groups were comparable.

Adult↗
PubMed1999

Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy.

In a recent phase II clinical study, 13 chronic hepatitis B-infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1-log10 decrease in plasma hepatitis B virus (HBV)-DNA levels. The decline of viral load during therapy displayed a biphasic kinetic profile that was modeled to determine the efficacy of inhibition of viral production, as well as kinetic constants for the clearance of free virus and the loss of infected cells. Viral production was suppressed with an efficacy of 0.993 +/- 0.008, indicating that only 0.7% of viral production persisted during therapy. The initial, faster phase of viral load decline reflects the clearance of HBV particles from plasma with a half-life of 1.1 +/- 0.3 days, translating to a 48% daily turnover of the free virus. The second, slower phase of viral load decline closely mirrors the rate-limiting process of infected cell loss, with a half-life of 18 +/- 7 days. The duration of therapy required to completely eliminate the virus from plasma or suppress it to levels sufficient to induce seroconversion is a function of the half-life of the free virus, the half-life of infected cells, and the efficacy of inhibition of virus production from infected cells. These quantitative analyses provide a more detailed picture of the dynamics of HBV infection and therapy, and can be used to compare the efficacy of various doses and inhibitors of HBV replication for the treatment of HBV infections.

Adenine↗
PubMed1998

Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults.

9-[2-(R)-(Phosphonomethoxy)propyl]adenine (PMPA) is a nucleotide analogue with potent antiretroviral activity in vitro and in simian models. A randomized, double-blind, placebo-controlled, dose-escalation clinical trial of intravenous PMPA monotherapy was conducted in 20 human immunodeficiency virus (HIV)-infected adults with CD4 cell counts of >/=200 cells/mm3 and plasma HIV RNA levels of >/=10,000 copies/ml. Two dose levels were evaluated (1 and 3 mg/kg of body weight/day). Ten subjects were enrolled at each dose level (eight randomized to receive PMPA and two randomized to receive placebo). On day 1, a single dose of PMPA or placebo was administered by intravenous infusion. Beginning on study day 8, PMPA or placebo was administered once daily for an additional 7 consecutive days. All subjects tolerated dosing without significant adverse events. Mean peak serum PMPA concentrations were 2.7 +/- 0.9 and 9.1 +/- 2.1 microgram/ml in the 1- and 3-mg/kg cohorts, respectively. Serum concentrations declined in a biexponential fashion, with a terminal half-life of 4 to 8 h. At 3 mg/kg/day, a single infusion of PMPA resulted in a 0.4 log10 median decline in plasma HIV RNA by study day 8. Following 7 consecutive days of study drug administration thereafter, the median changes in plasma HIV RNA from baseline were -1.1, -0.6, and 0.1 log10 in the 3-mg/kg/day, 1-mg/kg/day, and placebo dose groups, respectively. Following the final dose in the 3-mg/kg/day cohort, the reduction in HIV RNA was sustained for 7 days before returning toward baseline. Further studies evaluating an oral prodrug of PMPA are under way.

Adenine↗
PubMed1997

A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease.

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.

Adult↗
PubMed1996

Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.

A randomized controlled study was done to determine whether initial combination therapy with zidovudine and zalcitabine or zidovudine and didanosine would delay the emergence of zidovudine-resistant virus. Human immunodeficiency virus (HIV)-1-infected patients with <300 CD4 cells/mm3 and <4 weeks of prior zidovudine therapy were randomized to zidovudine, zidovudine plus zalcitabine, or zidovudine plus didanosine. Combination therapy did not delay the emergence of zidovudine-resistant virus isolates. However, combination therapy resulted in a significant increase in CD4 cells through 72 weeks compared with zidovudine monotherapy and a greater and more sustained decline in serum HIV-1 RNA. Although this trial was not designed as a clinical end-point study, patients assigned to zidovudine plus didanosine combination therapy experienced a significant delay in time to first AIDS-defining event or death compared with those assigned to zidovudine monotherapy.

Adult↗
PubMed1995

Psychological adaptation among residents following restart of Three Mile Island.

Psychological adaptation is examined in a sample of residents who remained in the vicinity of Three Mile Island following the restart of the nuclear generating facility which had been shut down since the 1979 accident. Findings indicate a lowering of psychological symptoms between 1985 and 1989 in spite of increased lack of control, less faith in experts and increased fear of developing cancer. The suggestion is made that reduced stress might have been related to a process of adaptation whereby a cognition of emergency preparedness was integrated by some of these residents as a modulating cognitive element. Findings also indicate that "loss of faith in experts" is a persistently salient cognition consistent with the "shattered assumptions" theory of victimization.

Adaptation, Psychological↗
PubMed1995

Transplantation of skin from human immunodeficiency virus type 1-transgenic mice to normal congenic mice results in graft rejection.

Skin from mice transgenic (Tg) for part of the human immunodeficiency virus type 1 (HIV-1) genome was transplanted onto normal mice of the same strain. All Tg grafts were rejected within 29 days. In contrast, skin from normal mice that was transplanted to HIV-1-Tg recipients remained viable for > 67 days. Histologic examination of Tg grafts on normal mice showed evidence of monocytic infiltrates. Monocytic infiltrates were not observed, however, when either normal or Tg skin was transplanted onto Tg mice. Immunohistologic staining verified the presence of gp120 protein expression in the Tg-transplanted skin but not in adjacent normal skin. It is concluded that the Tg mice are immunologically tolerant to the HIV-1 gene products they express.

Animals↗
PubMed1993

Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether oral acyclovir reduces the incidence of recurrent herpes labialis in otherwise healthy patients with proven frequently recurrent disease. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Outpatient facility of the Clinical Center, National Institutes of Health, Bethesda, Maryland. PATIENTS: Fifty-six otherwise healthy adults who reported frequently recurrent herpes labialis (> or = 6 episodes/y) were enrolled into the study. During a 4-month observation period, 22 patients had herpes labialis two or more times and were eligible for study treatment. INTERVENTIONS: Twenty-two patients were randomized to receive either acyclovir, 400 mg twice daily, or matched placebo for 4 months. After the first treatment period, patients were given the alternate treatment for another 4 months and were then taken off study medication to observe the first post-treatment recurrence. Recurrent outbreaks were determined by examination and by viral culture. RESULTS: Twenty patients completed blind treatment with both acyclovir and placebo. The median time to first clinically documented recurrence was 46 days for placebo courses and 118 days for acyclovir courses (P = 0.05). The mean number of recurrences per 4-month treatment period was 1.80 episodes per patient during placebo treatment and 0.85 episodes per patient during acyclovir treatment (P = 0.009). The mean number of virologically confirmed recurrences per patient was 1.40 with placebo therapy compared with 0.40 with acyclovir (P = 0.003). CONCLUSIONS: Oral acyclovir, 400 mg twice daily, is effective in suppressing herpes labialis in immunocompetent adults confirmed to have frequently recurrent infection. Treatment with acyclovir in this study resulted in a 53% reduction in the number of clinical recurrences and a 71% reduction in virus culture-positive recurrences compared with placebo therapy.

Acyclovir↗
PubMed1993

Cutaneous disorders and viral gene expression in HIV-1 transgenic mice.

Patients infected with HIV-1 experience several hyperproliferative skin disorders, including seborrheic dermatitis, ichthyosis, and psoriasis. Transgenic mice carrying a subgenomic HIV-1 proviral construct lacking the gag and pol genes were found to develop proliferative epidermal lesions, manifested as diffuse epidermal hyperplasia in homozygous transgenic mice and benign papillomas in heterozygous transgenic mice. Nonpapillomatous skin from both homozygotes and heterozygotes expressed viral RNA, and the viral envelope protein gp120 was localized to the suprabasal keratinocyte. Papillomas contained increased amounts of both viral mRNA and envelope glycoprotein. Exposure of transgenic mice to doses of ultraviolet B (UV-B) irradiation that induced cutaneous injury increased viral gene expression and resulted in the development of papillomas within 14-21 days. Cutaneous injury induced by phenol and liquid nitrogen had similar effects. These data support a role for HIV-1 gene products in the pathogenesis of proliferative epidermal disorders associated with HIV-1 infection. Further, they suggest that the process of wound repair increases HIV-1 gene expression in this transgenic mouse model.

Animals↗
PubMed1992

UV light-induced reactivation of herpes simplex virus type 2 and prevention by acyclovir.

UV B light is a potent stimulus for inducing reactivation of latent herpes simplex virus (HSV) infections. Patients were enrolled in a double-blind placebo-controlled crossover trial to determine whether acyclovir can prevent UV light-induced HSV-2 recurrences. Twenty-four patients with a history of recurrent infection of perigenital sites (e.g., buttock, thigh) were exposed one to four times with 4 minimum erythema doses of UV light. Patients were given acyclovir 200 mg orally five times daily or matched placebo beginning 1 day before each exposure and continuing for 5 days after exposure. There were 13 UV-induced recurrences among 36 placebo treatments and 3 after 38 acyclovir treatments (P = .004). The mean time to recurrence (+/- SE) was 4.8 +/- 0.3 days. HSV-2 lesions developed primarily at the site of UV exposure. The cutaneous distribution and timing of UV-induced recurrences was consistent with a neural localization (dorsal root ganglia) of latent viral infection. This UV light model permits direct examination of events leading to HSV-2 recurrences in humans and can be used to evaluate approaches to prevention.

Acyclovir↗
PubMed1991

Prevention of ultraviolet-light-induced herpes labialis by sunscreen.

Sunlight exposure is reported by some patients to precede onset of recurrent herpes labialis. Ultraviolet (UV) B light is known to be a stimulus for the reactivation of herpes simplex virus (HSV) infections. We assessed the effect of a sunblocking agent on UV-light-induced reactivation of recurrent herpes labialis in a double-blind, placebo-controlled crossover trial. 38 patients were exposed on two separate occasions to four minimum erythema doses of UV light at an area of previous labial herpes recurrence. A solution containing sunscreen was applied to the lips before one exposure and a matched placebo before the other. After placebo and UV exposure, herpes labialis developed in 27 (71%) of the 38 patients, with a mean time to recurrence of 2.9 (SEM 0.2) days. In contrast, when sunscreen was applied before UV exposure, no lesions developed, but 1 of the 35 patients shed virus at the exposure site. We conclude that UV light is a potent stimulus for inducing reactivation of herpes labialis, and that application of sunscreen may be effective in the prevention of sunlight-induced recurrent infection.

Adolescent↗
PubMed1991

Transplantation of syngeneic transfected cells to probe the in vivo immune response to viral proteins.

BALB/3T3 cells were transfected with the glycoprotein D (gD) gene of herpes simplex virus (HSV) and a cell line expressing gD on the cell surface was isolated. In vitro, 51Cr release tests showed that the transfected cells were destroyed by anti-HSV antibody in the presence of complement. To investigate in vivo immune response, the gD-transfected cells were transplanted into the footpads of syngeneic HSV-immunized or unimmunized BALB/c mice. In unimmunized mice, transfected cells remained intact for 7 days or longer, and the site of injection showed only slight lymphocyte infiltration. In contrast, in immunized mice, transfected cells elicited massive lymphocyte infiltration and were mostly destroyed by day 4. Analysis of infiltrating cells revealed that they were mainly Thy1+ and CD8+ lymphocytes along with small numbers of CD5+, CD4+, and B lymphocytes. These studies show that transfected murine cells expressing gD can be used to study the in vivo immune response to single viral proteins and they argue that the immune response contributes to the pathogenesis of HSV infection.

Animals↗
PubMed1990

Life stage differences in resident coping with restart of the Three Mile Island nuclear generating facility.

A study of residents who remained in the vicinity of Three Mile Island (TMI) immediately following the restart of the nuclear generating plant revealed that older residents employed a more emotion-focused coping style in the face of this event than did younger residents. Coping style was, however, unrelated to the level of psychological symptoms for these older residents, whereas demographic variables were related. Among younger residents, on the other hand, coping style was related to the level of psychological symptoms, whereas demographic variables were not. Among younger residents, emotion-focused coping was associated with more symptoms and problem-focused coping was associated with fewer symptoms, contradicting previous findings among TMI area residents.

Accidents↗