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Biomedical subjects

Y J Bryson

Publications and source records attributed to Y J Bryson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Antibody response to herpes simplex virus glycoproteins gB and gD.

The antibody response to herpes simplex virus (HSV) glycoproteins B and D was evaluated using these cloned glycoproteins in an ELISA assay and compared to a standard Western blotting procedure. The ELISA assay appeared to be more sensitive for detecting gB and gD antibodies. Antibodies to gB but not gD were detected in the acute sera of patients presenting with their first episode of true primary genital herpes. The geometric mean HSV gB titer (log 2) was also significantly higher than the geometric mean gD titer in the convalescent sera of these patients (7.9 +/- 0.7 vs. 5.5 +/- 0.9, P less than .003). A cross-reaction between HSV gB and varicella zoster virus (VZV) gp II was demonstrated. Thus, it is possible that a previous VZV infection could prime the immune system to respond rapidly and more vigorously to HSV gB. Indeed, in this report we demonstrated a significant correlation between the VZV ELISA absorbance and the titer to HSV gB and also detected a higher VZV ELISA absorbance and HSV gB titer in the acute sera of patients with a true primary HSV infection compared to other HSV seronegative VZV seropositive patients. Use of this quantitative assay should allow further investigation into the relationship of the immune response to these important targets and the clinical course of HSV disease.

Adult↗
PubMed1989

Comparison of intramuscular recombinant alpha interferon (rIFN-2A) with topical acyclovir for the treatment of first-episode herpes genitalis and prevention of recurrences.

Intramuscular recombinant alpha interferon (rIFN-2A; 9 million IU given for 5 days during a 9-day treatment period) was compared with topical acyclovir in a double-blind, placebo-controlled trial for the treatment of first-episode genital herpes simplex virus (HSV) infection and for subsequent alteration of the frequency of recurrences. rIFN-2A (within 96 h of onset of the first episode) was not superior to topical acyclovir in a well-matched group of 105 patients. The early use of rIFN-2A also did not alter the frequency or severity of genital HSV recurrences within either the first or second 6 months following therapy. Separate analyses by HSV type and by type of infection (primary versus nonprimary) did not change this conclusion. Furthermore, there was significant toxicity associated with rIFN-2A therapy. rIFN-2A is not indicated for the treatment of genital HSV infections.

Acyclovir↗
PubMed1988

Therapy of herpes zoster with oral acyclovir.

Oral acyclovir therapy for herpes zoster has been studied in double-blind, placebo-controlled trials of two dosages, 400 mg and 800 mg five times per day for 10 days. Compared with placebo recipients, recipients of the high-dosage acyclovir experienced a significantly shortened period of viral shedding, significantly accelerated time to 50 percent scabbing, significantly accelerated time to 50 percent healing, and after two days of therapy, significantly less frequent formation of new lesions. The duration and severity of acute pain were less in acyclovir recipients, with differences in pain severity achieving statistical significance (p = 0.03) between Days 3 and 10 and correlating with the treatment differences in new lesion formation. In studies of the 400 mg five times per day dose schedule, differences between acyclovir and placebo recipients were not significant. In a six-month follow-up of recipients in the higher dosage study, the acyclovir recipients experienced less post-zoster pain than placebo recipients; differences in the prevalence of pain were most significant for the presence of a persistent pain in the first three months of follow-up. Oral acyclovir at these dosages appears to be free of adverse reactions. In summary, oral acyclovir at a dosage of 800 mg five times per day for 10 days for treatment of acute herpes zoster is superior to 400 mg five times per day and favorably alters the course of the disease.

Acyclovir↗
PubMed1988

Intravenous acyclovir therapy of first episodes of genital herpes: a multicenter double-blind, placebo-controlled trial.

PURPOSE: A collaborative multicenter double-blind, placebo-controlled trial of intravenous acyclovir treatment of first-episode genital herpes was performed in order to substantiate previous findings on the efficacy and safety of this drug, to evaluate the influence of parenteral therapy on recurrence frequency, and to obtain further data on the natural history of genital herpes. PATIENTS AND METHODS: Eighty-two patients with first episodes of genital herpes simplex virus (HSV) infection were randomly assigned in a double-blind fashion to treatment with intravenous acyclovir (5 mg/kg every eight hours) or placebo for five days. Before therapy, all lesions in the genital/perineal area and in extragenital sites were cultured. New lesions appearing in both areas after the onset of therapy were cultured separately. Lesions in all groups were cultured until completely healed. Sera were collected from all patients on entry to the study and on Day 21 to determine presence or absence of antibodies to HSV-1 and HSV-2. Time to healing, time to crusting, time to cessation of viral shedding, and appearance of new lesions during therapy were compared for each treatment group. RESULTS: Patients receiving acyclovir experienced a significant reduction in the median duration of pain (4.3 versus 4.8 days, p = 0.019), viral shedding (1.9 versus 8.4 days, p less than 0.001), and time to healing (8.4 versus 11.5 days, p = 0.02) compared with placebo recipients. These differences were largely attributable to the effect of therapy in the subset of patients with primary disease in whom acyclovir reduced the median duration of pain from 10.6 days to 4.2 days, the median duration of viral shedding from 17.1 days to 1.9 days, and the median time to healing from 14.2 days to 8.3 days. The rate of subsequent recurrence of genital herpes was not altered by acyclovir treatment: 24 of 32 acyclovir recipients (75 percent) experienced one or more recurrences during a mean follow-up of 14 months compared with 19 of 27 placebo recipients (70 percent). Among patients experiencing recurrences, the mean number of recurrences per month among acyclovir recipients was 0.25 compared with 0.19 for patients given placebo. CONCLUSION: This multicenter trial confirms the efficacy of intravenous acyclovir in the management of first-episode genital herpes, especially in patients with primary infection. However, therapy did not alter the frequency of recurrences.

Acyclovir↗
PubMed1988

Promising new antiviral drugs.

We now have a basis for a more rational approach to rapid evaluation and development of antiviral drugs by screening for activity in vitro, testing for toxicity and efficacy in animals, and clinical testing in humans. Acyclovir is a prototype of this improved process. Interferon has a beneficial effect against CMV infection in renal transplant patients and has promising results in the treatment of papillomas and rhinovirus infections. It does not seem to be as effective against genital herpes or varicella zoster as acyclovir. Ribavirin is effective against respiratory syncytial virus infections and Lassa fever. Varicella-zoster virus is highly sensitive to bromovinyl deoxyuridine in vitro. Phosphonoformate is effective in herpes simplex in animals but of little clinical benefit topically in human recurrent A2 herpes. Zidovudine may decrease mortality rates and infectious complications in patients with acquired immunodeficiency syndrome. DHPG (9-(1,3-dihydroxy-2-propoxymethyl]guanine is useful in treatment of cytomegalovirus and infection in immunocompromised patients. The prodrug of acyclovir results in high blood levels of acyclovir and shows promise in the treatment of varicella-zoster infections. Many halogenated pyrimidine nucleoside analogs are being developed. Buciclovir is another acyclic guanosine analog effective against herpes simplex virus in vitro. 2'-nor-cyclic guanosine monophosphate has a broad antiviral spectrum of action. Interleukin-2 is being investigated. Combined therapies of two or more antiviral drugs or antiviral drugs and other treatments are being studied.

Acyclovir↗
PubMed1987

Treatment of cytomegalovirus retinopathy with ganciclovir.

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Suppression of recurrent genital herpes simplex virus infection with recombinant alpha 2 interferon.

This double-blind, placebo-controlled study evaluated the efficacy and safety of sc administered recombinant alpha 2 interferon (IFN-alpha 2) in the suppression of frequently recurrent genital herpes simplex virus (HSV) infection. Seventy-six otherwise healthy subjects who had eight or more recurrences during the preceding year received 1 X 10(6) IU of IFN-alpha 2, 3 X 10(6) IU of IFN-alpha 2, or placebo three times per week for 12 weeks. Recipients of the higher dose of IFN-alpha 2, had fewer outbreaks during the study (2 vs. 3), a shorter period of viral shedding (2 vs. 4 days), less itching (1 vs. 3 days), and a faster healing time (6 vs. 8 days). The lower dose of IFN-alpha 2 was not effective. Significant side effects (fever, malaise, myalgia, fatigue, and arthralgia) occurred after the first injection of 3 X 10(6) IU of IFN-alpha 2 in 91% of the subjects, but subsequent injections produced only mild and intermittent side effects that were well tolerated. Mild leukopenia was noted in subjects treated with IFN-alpha 2. Treatment with IFN-alpha 2 resulted in moderate suppression and decreased duration of recurrent genital HSV infection in patients with frequent recurrences.

Adult↗
PubMed1986

Respiratory pharmacology. Antiviral agents.

In summary, there are numerous clinically useful antiviral agents currently available, with many more investigational drugs on the horizon. The future of antiviral chemotherapy looks bright, and the principles behind successful therapy will remain the same. It is hoped that with the advent of effective therapy, improved rapid viral diagnosis and early treatment of patients will be possible to maximize beneficial effects.

Acyclovir↗
PubMed1985

Comparison of Western Blot Analysis to microneutralization for the detection of type-specific herpes simplex virus antibodies.

A newly developed system (as described in the previous paper) employing separated herpes simplex virus (HSV) polypeptides electrophoretically transferred to nitrocellulose paper, Western Blot Analysis (WBA), was compared to microneutralization (MN) for the detection of type-specific antibody to HSV types 1 and 2 in 98 human sera. Sera containing HSV1-specific antibodies reacted at least twofold more densely (as quantitated by densitometric scanning) to HSV1 than HSV2 polypeptides, while sera with HSV2-specific antibodies reacted twofold more densely to HSV2 polypeptides. The reliability of this system was determined (1) by analysis of sera from patients with true primary herpes simplex infections, (2) by adsorption studies that removed cross-reacting antibodies, and (3) by comparison with neutralization. Of 36 sera found to have HSV1-type-specific antibody by WBA, 83% had MN ratios of less than 85 (indicating HSV1 antibody), while of 28 sera found to have HSV2-type-specific antibody by WBA, 89% had MN ratios of greater than 85 (indicating HSV2 antibodies). The MN ratio obtained on sera felt to have both HSV1-type-specific and HSV2-type-specific antibody by WBA ranged from 67 to 160. WBA agreed more closely with clinical isolates and adsorption studies than MN. This system not only accurately determines the HSV-type-specific antibody status of patients but provides important information on the specific immunogenic proteins.

Antibodies, Viral↗
PubMed1985

Antibody response to type-common and type-unique epitopes of herpes simplex virus polypeptides.

Herpes simplex virus type 1 (HSV1) and type 2 (HSV2) polypeptides with type-common and type-unique epitopes were identified using cross-adsorbed hyperimmune rabbit sera and Western blotting techniques. Twelve HSV1 and fourteen HSV2 polypeptides with type-specific epitopes were identified. Cross-adsorbed human sera reacted to a subset of the type-specific epitopes defined by rabbit sera. Human sera with both HSV1- and HSV2-specific antibodies were identified by their reaction to HSV1-type-specific epitopes after adsorption with HSV2, and HSV2-type-specific epitopes after adsorption with HSV1. Mixing experiments demonstrated the sensitivity of this assay for detecting HSV2-type-specific antibody in the presence of HSV1 antibody. This technique has proven useful in the study of immune response to individual HSV polypeptides during human HSV infections, while the presence of these type-unique epitopes on HSV polypeptides allows for the detection of type-specific antibodies in human sera.

Antibodies, Viral↗
PubMed1985

Impaired production of gamma-interferon by newborn cells in vitro is due to a functionally immature macrophage.

The decreased production of gamma-(PHA-induced) interferon (IFN) by leukocytes of normal newborns could be due to functionally immature T cells, macrophages, or both. We studied gamma-IFN production by macrophages and T cells, alone and in combination, obtained from 50 cord blood samples and 14 adult blood samples in a series of experiments. Adherent macrophages were cultivated for 7 days before the addition of T cells. After 48 hr, PHA-stimulated macrophage-T cell supernatants were harvested and assayed for IFN by a microassay. Macrophage-T cell cultures of autologous and nonautologous cells in 14 adults showed enhanced IFN production (GMT 121 +/- 5 IU) as compared with Ficoll-Hypaque mononuclear cells (GMT 42 +/- 5 IU). No IFN was detected in supernatants from PHA-stimulated Ficoll-Hypaque cord cells alone or macrophage-T cord combined cultures. Combined cord macrophages and adult T cells produced minimal IFN (GMT 13 +/- 3 IU); however, cord T cells combined with adult macrophages showed enhanced IFN production (GMT 195 +/- 47 IU). This cord macrophage dysfunction was not due to an inhibitor and improved with the time of in vitro cultivation. These results indicate that the neonatal macrophage is primarily responsible for the impaired gamma-IFN response by the newborn cells.

Adult↗
PubMed1984

Serologic analysis of first-episode nonprimary genital herpes simplex virus infection. Presence of type 2 antibody in acute serum samples.

Acute serum samples from patients with nonprimary first-episode genital herpes were evaluated for the presence of type-specific antibody to herpes simplex virus type 1 and type 2. A standard microneutralization assay and western blot analysis, which identified the response to individual polypeptides of type 1 and type 2 herpes, were performed in both unadsorbed serum samples and serum samples adsorbed with either type 1 or type 2 antigens to remove cross-reacting antibodies. Of 24 serum samples examined, seven were found to contain only type 1 antibodies, 11 had type 2 antibodies alone, and six serum samples had both type 1 and type 2 antibodies. It is believed that a majority of the 17 patients whose acute serum samples already contained type 2 antibody were experiencing their first clinically apparent recurrence of a previous asymptomatic type 2 infection. Physicians should, therefore, acknowledge that patients with first-episode nonprimary herpes 2 infection may not have had a recent sexual contact with a herpes simplex virus-infected partner.

Acute Disease↗
PubMed1984

The effects of acyclovir on antibody response to herpes simplex virus in primary genital herpetic infections.

The humoral response to herpes simplex virus (HSV) was examined in 21 patients with primary HSV infection who were participating in a placebo-controlled trial of oral acyclovir as therapy for first-episode genital herpes. A standard microneutralization assay and a western blot analysis, which detects the antibody response to individual polypeptides of HSV types 1 and 2, were used. Placebo-treated, HSV type-2-infected patients typically responded to HSV type-2 polypeptides that had molecular masses of 125, 84, 68, 59, 46, and 40 kilodaltons. Treatment with acyclovir diminished the humoral response both to HSV, as measured by the type-specific neutralizing-antibody titer, and to specific polypeptides, especially those with molecular masses of 50-100 kilodaltons, a range that includes polypeptides with molecular masses corresponding to those of glycoproteins D and E of HSV.

Acyclovir↗
PubMed1984

Comparison of monoclonal and polyclonal antibody for confirmation of cytomegalovirus isolates by fluorescent staining.

A fluorescein isothiocyanate-labeled monoclonal cytomegalovirus antibody reagent incorporating Evans blue (Syva/Genetic Systems, Palo Alto, Calif.) was compared to a fluorescein isothiocyanate-labeled polyclonal antibody (Dynatech Diagnostics, Inc., South Windham, Maine) for identification of cytomegalovirus in tissue culture. A total of 191 cultures, 86 positive and 105 negative for cytomegalovirus by cytopathic effect in WI38 cells, were stained in parallel and examined by fluorescent microscopy. No false-negative results were noted with either reagent; however, the polyclonal antibody-stained slides required the use of a separate counterstain to decrease nonspecific fluorescence. The polyclonal reagent gave a false-positive reaction with one varicella-zoster virus isolate and four simian cytomegalovirus isolates. No false-positive results were noted with the monoclonal reagent.

Antibodies, Monoclonal↗
PubMed1983

Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects.

We performed a double-blind placebo-controlled trial of oral acyclovir in the treatment of first episodes of genital herpes simplex virus infections in 48 young adults (31 women and 17 men). Subjects were randomized to receive either placebo or acyclovir (200 mg per dose) five times daily for 10 days; they were examined on at least eight visits until healed and at monthly visits thereafter. Acyclovir treatment, as compared with placebo, significantly reduced virus shedding, new lesion formation after 48 hours, and the duration of genital lesions in both men and women. The total duration and severity of clinical symptoms (such as pain, adenopathy, dysuria, and malaise) were significantly reduced by acyclovir in both men and women by the third and fourth day, respectively (P less than or equal to 0.025), as compared with placebo. No toxicity was observed. Recurrence rates have so far been similar in placebo and acyclovir recipients. Oral acyclovir treatment of first-episode genital herpes simplex virus infections is clinically effective, but it does not seem to prevent virus latency or associated recurrent disease.

Acyclovir↗