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Biomedical subjects

Y J Bryson

Publications and source records attributed to Y J Bryson.

At least 73 records · Page 4Linked to original sources

Current status and prospects for oral acyclovir treatment of first episode and recurrent genital herpes simplex virus.

Herpes simplex genitalis is an increasingly common primary or recurrent HSV infection. Acyclovir (ACV) has been found to diminish virus shedding and clinical symptoms in patients with first episode genital HSV when given topically or intravenously. As most patients with first episode disease do not require hospitalization and recurrent disease is usually less severe than the primary infection, out-patient treatment forms the basis of practical management. Acyclovir is absorbed orally with plasma concentrations which exceed in vitro inhibitory concentrations for HSV1 and HSV2. In double blind studies in over 100 recipients with first episode HSV, oral ACV treatment (200 mg, 5 times daily) significantly reduced virus shedding, new lesion formation, duration of genital lesions and clinical symptoms in both men and women when compared with placebo recipients. No toxicity was observed. Recurrence rates following the first episode were similar in placebo and ACV groups. A multi-centre double blind trial of oral ACV treatment of recurrent HSV infection in 250 patients showed that the duration of virus shedding and lesions was significantly shorter in ACV versus placebo recipients. These effects were more pronounced when therapy was self-initiated by patients early on during a recurrence or during the prodromal period. Oral acyclovir has significant clinical and virological effects in both primary and recurrent genital HSV infections.

Acyclovir↗

Deficient lymphokine production of newborn lymphocytes.

Lymphokine production by newborn lymphocytes was assessed by measuring migration inhibition factor (MIF) and leukocyte inhibition factor (LIF) of isolated mononuclear cells from cord blood, 1-7-days-old newborns, and adult controls. Ficoll-Hypaque separated mononuclear cells were stimulated with phytohemagglutinin (PHA) or allogeneic lymphocytes in a mixed leukocyte culture (MLC), and the supernatants were harvested at optimal times for lymphokine assays. Thymidine incorporation into DNA was also assayed to calculate a proliferative index. MIF was assessed by the inhibition of adult mononuclear phagocyte cell migration under agarose; LIF was assessed by polymorphonuclear cell migration under agarose. Although the proliferative responses of cord and newborn cells are equivalent or greater than those of adult controls, the PHA-induced MIF production in cord blood and newborn lymphocytes was only 46% and 12.5% respectively of mean adult levels; MLC-induced MIF production was 44% and 7%, respectively of mean adult levels. PHA-induced LIF production in cord blood was 27% of adult levels. These differences are only appreciated if dilutions of the supernatants are assayed. Simultaneous assay of MIF and LIF production in dilution of supernatants from adult lymphocytes showed higher LIF activity, whereas in cord lymphocytes MIF activity was greater than LIF activity. This further emphasizes the non-identity of MIF and LIF. These results indicate another abnormality of T cellular immunity in newborns not detected by T-cell enumeration or proliferative responses and parallels other defects in specialized T cell function such as cytotoxicity and immune interferon production.

Fetal Blood↗

Treatment of cytomegalovirus pneumonia after marrow transplant with combined vidarabine and human leukocyte interferon.

Seven marrow transplant recipients were treated with human leukocyte interferon and vidarabine for cytomegalovirus pneumonia. Although the mean virus titer in biopsy and autopsy lung specimens from five patients decreased from 5 x 10(4) to 1 x 10(2) 50% tissue culture infective doses, there was little clinical evidence of efficacy and only one patient survived. Treatment was stopped in four patients because of declining neutrophil counts, and two of these four patients also showed severe neurotoxicity. The combination of these agents was neither safe nor effective for the treatment of cytomegalovirus pneumonia after marrow transplantation.

Bone Marrow Transplantation↗

Double-blind controlled study of central nervous system side effects of amantadine, rimantadine, and chlorpheniramine.

A total of 52 healthy, adult volunteers were randomly assigned to five treatment groups to be treated twice daily for 4 days with 100 mg of amantadine, 100 mg of rimantadine, 4 mg of chlorpheniramine or placebo alone, or 100 mg of amantadine in combination with chlorpheniramine. The results of tests measuring performance on tasks of attention, reasoning, and memory were unaffected by treatment. Subjective side effects in recipients of amantadine, rimantadine, and chlorpheniramine were comparable and minimal. Side effects appeared to be enhanced in subjects receiving both amantadine and chlorpheniramine.

Adamantane↗

Necrotizing vasculitis in a case of disseminated neonatal herpes simplex infection.

A term newborn suffered disseminated herpes simplex virus (HSV) type II infection five days after cesarean section delivery for fetal distress. The mother had no history or evidence of herpetic lesions; the father had a history of genital herpetic lesions. The infant's terminal course was dominated by disseminated intravascular coagulation (DIC) with hepatic and renal failure. Microscopic examination revealed a necrotizing vasculitis of small and medium-sized lung and peripancreatic arteries. Nuclear inclusions characteristic of HSV were found in these arteries, as well as in the adrenal parenchyma, spleen, and lymph node; electron microscopy confirmed replication of virus within the arterial endothelial cells. The mechanism of arterial damage in severe herpetic infection contrasts with the immune-complex mechanism postulated for other viral vasculitides. Direct, virally induced arterial damage resulting in exposure of collagen may set the stage of DiC, a commonly fatal complication of this disease.

Arteries↗

Virus inhibition assay for measurement of acyclovir levels in human plasma and urine.

A simple microplate virus inhibition assay which measures the levels of acyclovir in plasma and urine samples from patients was developed. The assay is based upon the inhibition of the cytopathic effect of herpes simplex virus type 1 on human fibroblast cells. The extent of inhibition of virus cytopathic effect, caused by dilutions of samples from patients, allowed determination of acyclovir concentrations to be made. The assay, which measured biological activity, could detect acyclovir levels of greater than or equal to 1.0 microM. Peak and valley levels measured in plasma samples from two patients were comparable to values obtained by radioimmunoassay. The assay is simple, rapid, and quantitative, and it can be adapted to routine use for a large number of specimens.

Acyclovir↗

Lymphokine production by human milk lymphocytes.

To assess the functional capability of human milk lymphocytes, we studied phytohemagglutinin-induced lymphokine production by breast milk and, for comparison, peripheral blood lymphocyte cultures. Two lymphokines, lymphocyte-derived chemotactic factor (LDCF) and immune interferon, were assayed in supernatants of milk and blood lymphocyte cultures obtained from women 2 to 6 days postpartum. Eleven parallel milk and blood samples were studied for LDCF production. In nine experiments, both milk and blood lymphocytes produced LDCF. In the two other experiments, milk cells did not produce LDCF. In 10 milk cultures studied, all produced interferon activity. Acid and heat lability characteristics were typical of immune interferon. These results further characterize milk lymphocytes as immunologically competent and possibly important effector cells in neonatal immunity.

Animals↗

A prospective double-blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis.

During a study of efficacy of amantadine prophylaxis of influenza A virus infection in young adults, gross and subtle side effects were monitored. Eighty-eight students were randomly selected to receive either amantadine or placebo for four weeks or both in a sequential crossover design of two weeks each. Side effects (i.e., dizziness, nervousness, and insomnia) occurred in 33% of those receiving amantadine and in 10% of those receiving placebo (P less than 0.005). Although side effects were well tolerated by most subjects, six volunteers discontinued amantadine because of marked complaints. Cessation of side effects occurred in more than half of those continuing amantadine. Sixteen students receiving amantadine had decreased performance on sustained attention tasks as compared with ones receiving placebo (P less than 0.05). Gross and subtle side effects of amantadine observed in this study on currently recommended dosage are higher than previously reported, which may be an important factor in consideration of mass prophylaxis.

Adolescent↗

Epidemic measles in young adults. Clinical, epidemiologic, and serologic studies.

An outbreak of measles at the University of California at Los Angeles provided the opportunity to study clinical, epidemiologic, and serologic characteristics of the disease in young adults in the present vaccine era. Of the 34 cases studied, 18 occurred in persons who thought they were immune. Fifteen of 19 seronegative students vaccinated during the epidemic responded with a secondary (IgG) antibody response. Antibody prevalence studies indicated that 91% of the student population had measles antibody at the onset of the outbreak, and history relating to measles correlated poorly with antibody prevalence. Of 212 adults vaccinated, 58% complained of one or more symptoms. Seventeen percent were confined to bed, and in three women vaccine-associated illness was notably severe. That measles will continue to be a problem in adults with our present national approach to immunization is predicted.

Adolescent↗

Cellular (T cell) immunity in the human newborn.

The cellular immune system of the human newborn, like the rest of the immunologic apparatus, is anatomically intact, antigenically inexperienced, and functionally deficient. The latter is suggested by the newborns' enhanced susceptibility to infection, diminished delayed cutaneous hypersensitivity reactions, and selective abnormalities (when compared to adults) of measures of cellular immunity in vitro. These include impaired proliferative response to ubiquitous antigens, depressed lymphotoxin, migration inhibition factor, and immune interferon production, and diminished cytotoxic reactions including cell-mediated lympholysis. By contrast, other aspects of neonatal T cell function, such as to mitogens or allogeneic lymphocytes, natural interferon and leukocyte inhibition factor production, and number and percentage of E-rosette-forming cell are generally normal. These decreased functional properties may provide an explanation for the newborns' susceptibility to infection and for the occasional occurrence of engraftment of foreign cells from either the mother or from prenatal or neonatal blood transfusion.

Cytotoxicity, Immunologic↗

Simple sensitive microbioassay for adenine arabinoside and hypoxanthine arabinoside in human plasma.

Previous methods using low- or high-pressure liquid chromatography and UV absorbance for quantitation of arabinosides in plasma can practically detect only >/=200 ng of adenine arabinoside and >/=100 ng of hypoxanthine arabinoside per ml, and they require expensive equipment and expert technical assistance. We describe in this report a simple quantitative microbioassay for arabinosides in human plasma based on their ability to inhibit the cytopathic effect of vaccinia virus in an adenosine deaminase-free cell culture system. Using prior separation of nucleosides in plasma by thin-layer chromatography, followed by the microbioassay, we quantitated adenine arabinoside with a sensitivity of approximately 4 ng/ml and hypoxanthine arabinoside at approximately 625 ng/ml. This assay method is simple, sensitive, and reproducible, requires small plasma samples, measures biological activity, and is adaptable to routine use. It is an important tool for evaluating the pharmacology of adenine arabinoside and Ara-AMP in patients in current clinical trials.

Humans↗

Clinical trials with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza vaccines in Los Angeles children.

Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind, placebo-controlled protocols. One- and two-dose regimens employing monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) vaccine were studied in separate trials. In a single dose, whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus. Split-product vaccines were better tolerated clinically and, after two-dose regiments, produced rates of seroconversion (greater than 90%) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines. Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus. After vaccination with bivalent vaccines, levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines.

Adolescent↗

IgM and IgG antibody responses after immunization of children with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza virus vaccines.

The character of the immune response to inactivated monovalent influenza A/New Jersey/76 and bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines was studied in children six months to 18 years of age. Titers of hemagglutination-inhibiting antibody in sera taken after vaccination were measured before and after treatment with 2-mercaptoethanol. IgG antibody predominated in responses to the influenza A/Victoria/75 component of bivalent vaccines. In contrast, specific IgM antibody to influenza A/New Jersey/76 virus developed after administration of both monovalent and bivalent vaccines and appeared to characterize the immune response to this antigenic "shift" strain in children. Prevalences of IgM antibody against influenza A/New Jersey/76 virus did not differ significantly by age. This finding implies that type rather than extent of previous experience with influenza determines the IgM antibody response to an antigenic "shifts." Split-product vaccines produced significantly fewer IgM antibody responses to influenza A/New Jersey/76 virus than did whole-virus vaccines, a phenomenon that may correlate with their diminished reactogenicity and immunogenicity in children.

Adolescent↗

Combined antiviral effects of interferon, adenine, arabinoside, hypoxanthine arabinoside, and adenine arabinoside-5'-monophosphate in human fibroblast cultures.

Adenine arabinoside and human interferon are currently being evaluated in clinical trials against herpes- and poxvirus infections. Interferon production is also a normal antiviral response. It is therefore important to examine the combined actions of interferon and antiviral arabinosides for possible synergy or antagonism. We have examined the antiviral activities of human fibroblast interferon, adenine arabinoside, hypoxanthine arabinoside, and adenine arabinoside 5'-monophosphate individually, using plaque inhibition of vaccinia and herpes simplex type 2 viruses in human skin fibroblast cultures. By combining doses of interferon and arabinosides that, acting alone, give intermediate degrees of plaque inhibition, we were able to compare the combined antiviral activity with that calculated from the activity of each inhibitor alone, assuming that the activities are statistically independent. Our results show that the plaque-inhibitory activities of interferon and the arabinosides tested are statistically independent. The results also show that the arabinosides do not destabilize the antiviral state previously induced by interferon, and that interferon pretreatment does not interfere with subsequent arabinoside action in infected cells. We have also found that arabinosides do not affect the induction of interferon synthesis by either Newcastle disease virus or double-stranded ribonucleic acid, and are not themselves interferon inducers.

Antiviral Agents↗

In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside.

The in vitro susceptibility of varicella zoster (VZ) isolates to adenine arabinoside (ara-A) and hypoxanthine arabinoside (ara-Hx) was determined in human skin fibroblasts. Using a system in which deamination was inhibited, and using a modified plaque reduction method, the antiviral activities of ara-A and ara-Hx were separated. The plaque inhibitory concentration of ara-A for all VZ isolates tested was 1 to 2 mug/ml and 80 to 100 mug/ml for ara-Hx. A comparison of antiviral activity based upon total plaque suppression gave a rate of 40 to 50:1, in favor of ara-A.

Culture Techniques↗

Early treatment with acyclovir for varicella pneumonia in otherwise healthy adults: retrospective controlled study and review.

The effect of early acyclovir therapy on the course of varicella pneumonia in previously healthy adults was assessed. Medical records from five university-affiliated medical centers were retrospectively reviewed; included were all immunocompetent adults with a clinical diagnosis of primary varicella, a chest radiograph consistent with varicella pneumonia, and an arterial blood gas measurement indicating significant hypoxia. Of the 38 patients who met the study criteria, 11 had had a course of intravenous acyclovir initiated within the first 36 hours of hospitalization; the mean time from admission to initiation of therapy in this early-treatment group was 9.6 hours. The group that received early acyclovir treatment had a lower mean temperature beginning on the fifth day of hospitalization (37.0 degrees C vs. 37.7 degrees C; P = .011) and a lower mean respiratory rate beginning on the sixth day of hospitalization (21 vs. 28 respirations per minute; P = .004). Early acyclovir therapy also resulted in a significant improvement in oxygenation beginning on the sixth day of hospitalization in patients with follow-up arterial blood gas measurements (P = .035). Thus, early institution of acyclovir therapy is associated with reduction in fever and tachypnea and improvement in oxygenation in otherwise healthy adults with varicella pneumonia.

Acyclovir↗