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Biomedical subjects

J A Englund

Publications and source records attributed to J A Englund.

At least 73 records · Page 4Linked to original sources
PubMed1991

Acyclovir therapy in neonates.

STUDY OBJECTIVE: To determine the pharmacokinetic parameters of acyclovir disposition in neonates with renal dysfunction. DESIGN: Prospective sequential open enrollment of neonates with presumed herpes group virus infections. SETTING: Neonatal intensive care units in the greater Minneapolis-St. Paul metropolitan area. PATIENTS: Sixteen neonates with gestational ages between 27 and 40 weeks (median 38 weeks) were given acyclovir between days 1 and 56 of life to treat presumed herpes virus infections. Six infants were critically ill with multisystem disease, five infants had hepatic failure and underwent blood exchange transfusion, and five infants had renal failure. A mean of four (range 1 to 19) serum acyclovir concentrations per patient were measured by radioimmunoassay. Pharmacokinetic parameters were calculated from acyclovir concentrations in 46 samples from 16 patients. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetic disposition of acyclovir was described as a two-compartment model. Although the ranges for acyclovir clearance and terminal elimination (t 1/2 beta) were wide, a statistically significant relationship was demonstrated between clearance and beta versus serum creatinine concentration. The average t 1/2 beta for infants with serum creatinine level less than 1 mg/dl (88 mumol/L) was 5.0 hours, and 15.6 hours for those with serum creatinine level greater than 1 mg/dl. CONCLUSIONS: Neonates with hepatic or renal dysfunction or young premature infants accumulate acyclovir when dosed without adjustment for organ dysfunction. Measurement of serum creatinine or creatinine clearance can be useful in the dosing of acyclovir in neonates.

Acyclovir↗
PubMed1991

Pharmacologic basis for high-dose oral acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients.

The incidence of cytomegalovirus disease, the most important infectious complication of renal transplantation, was reduced in renal allograft recipients by a regimen of prophylactic high-dose oral acyclovir. To analyze the pharmacologic aspects of our prophylactic approach, we evaluated safety, pharmacodynamics, and in vitro susceptibility data. One hundred four recipients of cadaveric renal allografts received either oral acyclovir (n = 53) in doses of up to 3,200 mg/day or a placebo (n = 51) for 12 weeks posttransplant. Leukocyte count and serum creatinine were selected as markers of laboratory safety and were evaluated pretransplant, at study midpoint (creatinine only), and at study completion. Concentrations of acyclovir in plasma were determined to verify the ability of the dosing strategy to achieve predicted values. Viral resistance was assessed by calculation of in vitro 50% inhibitory concentrations (IC50s) of acyclovir for the cytomegalovirus strains collected from the subjects. Our results showed no difference in leukocyte count or serum creatinine between the acyclovir and placebo recipients. Plasma acyclovir concentrations were maintained within the expected limits and did not differ between patients who developed cytomegalovirus disease and those who did not. The mean acyclovir IC50s for cytomegalovirus isolates were 42.6 mumol/liter in the acyclovir recipients and 48 mumol/liter in the placebo recipients. We conclude that the clinical benefit of high-dose oral acyclovir therapy occurred despite plasma drug concentrations below the mean IC50 for the patient viral isolates. Furthermore, the use of the regimen did not produce leukopenia, adversely affect renal function, or alter the susceptibility of cytomegalovirus strains to acyclovir. This approach and dose adjustment scheme may be appropriate for other immunocompromised patients at risk for cytomegalovirus infection and disease.

Acyclovir↗
PubMed1991

Nosocomial transmission of respiratory syncytial virus in immunocompromised adults.

Respiratory syncytial virus (RSV) isolates obtained from nine infected immunocompromised adult patients hospitalized during two consecutive winters (January through April 1987 and 1988) were collected and analyzed against a panel of monoclonal antibodies by an enzyme immunoassay. The history of the patients' illness, onset of symptoms, and date of initial isolation of virus was correlated with the hospital ward and time of hospitalization. Three patients died of respiratory failure related to RSV infection acquired nosocomially. A cluster of RSV disease in four patients hospitalized simultaneously during the 1987 season was demonstrated to be caused by four antigenically distinct viruses; despite an epidemiologic link among the patients, each had been infected from a different source. The RSV disease in the five immunocompromised adults in 1988 was caused by two distinct strains; three patients were infected with RSV subgroup A/4, and two were infected with RSV subgroup B/2. Combining the epidemiologic and strain characterization studies, none of four patients in 1987 were infected from each other, and two of five patients in 1988 may have been infected, directly or indirectly, from one of the other five. The strain characterization studies demonstrated the potential complexity of RSV nosocomial transmission and the need to consider a number of sources for transmission in developing effective prevention strategies. The three deaths underscore the importance of nosocomial RSV disease and the importance of effective prevention strategies.

Adult↗
PubMed1990

Herpes simplex virus resistant to acyclovir. A study in a tertiary care center.

STUDY OBJECTIVE: To determine the sensitivity of herpes simplex virus isolates to acyclovir and the importance of resistant isolates in hospitalized patients. DESIGN: Retrospective incidence cohort study. SETTING: All herpes simplex virus isolates cultured over 1 year from patients followed at a tertiary care center. PATIENTS: Consecutive herpes simplex virus isolates were collected from 207 patients, including immunocompetent patients, patients with malignancy, neonates, bone marrow and organ transplant recipients, and patients seropositive for human immunodeficiency virus. MEASUREMENTS AND MAIN RESULTS: A rapid nucleic acid hybridization method was used to assess susceptibility to acyclovir. Acyclovir-resistant herpes simplex viruses were recovered from 7 of 148 immunocompromised patients (4.7%) but from none of 59 immunocompetent hosts. Clinical disease was found in all 7 patients with resistant herpes simplex virus and was more severe in pediatric patients. All resistant isolates were from acyclovir-treated patients and had absent or altered thymidine kinase activity by plaque autoradiography. CONCLUSION: Herpes simplex virus resistant to acyclovir arises relatively frequently in immunocompromised patients and may cause serious disease. Rapid detection of resistance permits antiviral therapy to be individualized. Antiviral susceptibility testing to monitor viral resistance should be encouraged, especially in tertiary care settings.

Acyclovir↗
PubMed1990

High-dose, short-duration ribavirin aerosol therapy in children with suspected respiratory syncytial virus infection.

Nine children (aged 6 weeks to 7 years) with suspected respiratory syncytial virus infection received aerosal treatment with ribavirin, 60 mg/ml for 2-hour periods three times daily for up to 5 days. Five children received treatment via an endotracheal tube and four via an oxygen hood. Blood samples (3 to 17 per patient) and respiratory secretions (4 to 23 per patient) were assayed for ribavirin with reverse-phase high-performance liquid chromatography. Ribavirin triphosphate in erythrocytes was determined by ion-exchange high-performance liquid chromatography. The mean (+/- SD) peak ribavirin level after the first dose was 1725 +/- 2179 mumol/L in secretions and 3.8 +/- 2.6 mumol/L in plasma. Ribavirin in the secretions was rapidly cleared, with a mean (+/- SD), half-life of 1.9 +/- 0.8 hours. Plasma ribavirin increased with treatments to reach a steady state of 5 to 10 mumol/L. Mean peak ribavirin triphosphate levels were 15- to 300-fold higher than plasma ribavirin levels by the end of therapy. More than 98% reduction of viral load without the emergence of resistant virus was noted on day 3 of therapy. High-dose treatment was compatible with the aerosol equipment routinely used (small-particle aerosol generator, model 2-6000) for ribavirin administration and with ventilators. High-dose, short-duration ribavirin therapy was well tolerated by all patients, permitted easier accessibility for patient care, and may result in less environmental exposure of health care workers.

Administration, Inhalation↗
PubMed1990

Acyclovir treatment of varicella in otherwise healthy children.

STUDY OBJECTIVE: To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Patients' residence and university hospital clinic. PATIENTS: One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo. INTERVENTION: Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later. CONCLUSIONS: These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children.

Acyclovir↗
PubMed1990

Acyclovir treatment for varicella does not lower gpI and IE-62 (p170) antibody responses to varicella-zoster virus in normal children.

The varicella-zoster virus (VZV) membrane glycoprotein gpI elicits a major immunoglobulin G antibody response after naturally acquired VZV infection; antibody to a nonglycosylated immediate-early protein, IE-62 (p170), represents a response to a nonmembrane VZV component. We evaluated antibody response to VZV gpI and IE-62 (p170) at 28 days and 1 year following infection in 34 children (ages 5 to 16 years) enrolled in a randomized placebo-controlled study of oral acyclovir for the treatment of varicella. All children were VZV antibody negative at enrollment, were previously healthy, and had laboratory-documented varicella. Compared with placebo recipients, acyclovir recipients had lower geometric mean titers by the fluorescent antibody to membrane antigen technique at 28 days (620 versus 836) but similar titers at 1 year (122 versus 122). All children had antibodies to gpI and IE-62 detectable by enzyme-linked immunosorbent assay at 28 days and 1 year. No difference in gpI at 28 days compared with 1 year was noted in acyclovir recipients. No difference in antibody to IE-62 (p170) was noted when acyclovir and placebo recipients were compared at either 28 days or 1 year. Antibody responses to gpI and IE were similar when children were stratified by age (5 to 6 years, 7 to 11 years, 12 to 16 years). A short course of oral acyclovir for the treatment of varicella did not affect antibody responses to gpI or IE-62 (p170) in healthy children at 28 days and 1 year following varicella.

Acyclovir↗
PubMed1989

Antiviral drugs in pediatrics.

Pediatricians are made familiar with antiviral drugs and are provided with specific recommendations for treatment of viral diseases. The antiviral drugs in clinical use today are discussed in terms of their doses, routes of administration, mechanisms of action, established and potential efficacies, and toxicities. These drugs include acyclovir, amantadine, trisodium phosphonoformate, ganciclovir, ribavirin, rimantadine, vidarabine, and zidovudine. Biologic response modifiers, such as interferons, are mentioned briefly in their historical context. Future trends in antiviral therapy are anticipated with mention of the most promising candidate compounds currently in preclinical trials.

Acyclovir↗
PubMed1989

Placebo-controlled trial of varicella vaccine given with or after measles-mumps-rubella vaccine.

A placebo-controlled study of varicella vaccine given either with or 6 weeks after measles-mumps-rubella (MMR) vaccine was undertaken in healthy children (mean age 16 months). A total of 101 varicella-zoster virus antibody-negative children completed the study. Serologic response to MMR vaccine was excellent (nearly 100%) and not significantly affected by the administration of varicella vaccine. Seroconversion in response to varicella vaccine was excellent and was not affected by MMR vaccine. No significant differences in fever or skin rashes between those receiving MMR vaccine with varicella vaccine or MMR vaccine with placebo were noted, but fever and skin rashes were more frequent after the first immunization (MMR with varicella vaccine or MMR vaccine with placebo) compared with the second (varicella vaccine or placebo injection). Symptoms of fatigue, irritability, and upper respiratory tract infections were more common after MMR vaccine was given regardless of whether it was given simultaneously with varicella vaccine or placebo injection.

Antibodies, Viral↗
PubMed1989

Respiratory syncytial virus-induced acute lung injury in adult patients with bone marrow transplants: a clinical approach and review of the literature.

Acute lung injury induced by respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in patients who have undergone bone marrow transplantation. Twenty-nine of the 74 patients who received bone marrow transplants at the University of Minnesota during a 1-year period developed evidence of acute lung injury, and RSV was identified as the cause in 8. We discuss the clinical course of these 8 patients and offer a clinical approach to RSV infection occurring after bone marrow transplantation. We also review the immune response to infection with RSV and relate this information to the nature and degree of immunosuppression present in patients undergoing this type of transplantation. We found bronchoalveolar lavage with rapid antigen detection to be particularly useful for the prompt diagnosis of this serious infection. The virus was obtained from the lower respiratory tract of each patient and was identified in lavage effluent by culture and by antigen detection (ELISA). The mean time to a positive culture was 6 days, while detection of antigens of respiratory syncytial virus by ELISA was completed within 18 hours in all cases. The clinical progression of the illness in immunocompromised patients appears to be the same as in non-immunocompromised persons: upper respiratory tract infection and illness precede lower respiratory tract infection and acute lung injury. Seven of our 8 patients had upper respiratory tract symptoms or abnormal sinus radiographs, and upper respiratory specimens (cultures and ELISA from nasopharynx, throat, and sputum) were positive in 5 of 8 patients. Six patients developed RSV-induced lung injury before marrow engraftment; 4 of them had respiratory failure requiring mechanical ventilation and died, including 3 in whom RSV was eliminated from the lower respiratory tract following treatment with ribavirin aerosol. Two additional pre-engraftment patients had only relatively mild lung injury 4 days after beginning treatment with ribavirin for RSV infection in the upper respiratory tract. Their recovery suggests that early treatment may ameliorate RSV-induced lung injury. The remaining 2 patients developed lung injury after marrow engraftment. Both of these patients had clear chest radiographs, responded clinically to ribavirin, and survived. RSV is a potentially treatable cause of life-threatening lung injury, if the physician is aggressive in identifying the virus in the upper respiratory tract before evidence of lung injury appears. Rapid detection methods are essential when bone marrow transplant patients have fever along with signs, symptoms, or radiographic indications of nasal or sinus disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Continuous infusion of high-dose acyclovir for serious herpesvirus infections.

Thirteen patients with herpesvirus infections who were unresponsive to at least 72 h of intermittent acyclovir administration received high-dose continuous infusion. Steady-state concentrations were maintained at between 20 and 98 mumol/liter. Of 12 patients who had continuous infusion for greater than 5 days, 7 (58%) resolved their infections, as determined by clinical and virologic parameters, suggesting that continuous infusion may succeed in some patients who do not respond to conventional therapy.

Acyclovir↗
PubMed1989

Recovery of human immunodeficiency virus type 1 from supernatant fluid of routine viral cultures.

Peripheral blood mononuclear cell samples from human immunodeficiency virus (HIV) antibody-positive subjects were inoculated into cell cultures used for routine viral isolation to determine if HIV could survive in them. HIV was recovered from 5 (19%) of 26 day 1 supernatants and from four of the five samples in all three types of cell cultures. We conclude that HIV may survive for at least 24 h in standard virology cell culture systems and therefore is a potential risk for laboratory personnel.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus disease was documented in 11 immunocompromised adults, aged 21 to 50. Underlying conditions included bone marrow transplant (6 patients), renal transplant (3 patients), renal and pancreas transplants (1 patient), and T-cell lymphoma (1 patient). Diagnosis of infection was based on specimens from bronchoalveolar lavage, sputum, throat, sinus aspirate, and lung biopsy. The virus was detected simultaneously by antibody in either an immunofluorescence or enzyme-linked immunosorbent assay in 3 of 4 patients whose culture results were positive for respiratory syncytial virus. The virus was an unexpected finding, despite widespread infection in the community. Clinical symptoms included low-grade fever, nonproductive cough, rhinorrhea or nasal congestion, and radiographic evidence of interstitial infiltrates and sinusitis. Aerosolized ribavirin therapy was used in the 6 recipients of bone marrow transplants, 3 of whom required assisted ventilation but died. Death caused by virus infection was documented in 4 of 11 patients. Respiratory syncytial virus disease must be considered in the differential diagnosis of fever and pulmonary infiltrates in immunocompromised adults.

Adult↗
PubMed1988

The many faces of Epstein-Barr virus.

Epstein-Barr virus (EBV) persists for life in a person who has been infected. Investigators are uncertain what this means to the host, particularly an immunocompromised one. EBV is the most common cause of infectious mononucleosis, but the diagnosis must be based on clinical, hematologic, and serologic criteria because other agents are the cause in about 10% of cases. EBV is the first virus to be associated with a neoplasm--Burkitt's lymphoma. This childhood malignancy is relatively common in central Africa, and EBV is a cofactor in its development, although direct evidence for a causal relationship has not been found. In southern China, nasopharyngeal carcinoma is an important health problem in adults in areas where the infection rate of EBV in childhood is high. Rare cases of primary EBV infection that evolved into uncontrolled lymphoproliferative disease have also been reported. EBV's relationship to these diverse diseases, its varying effects on certain individuals and in certain geographic locations, and the testing of a vaccine against the virus are areas of ongoing study.

Adolescent↗
PubMed1987

Cytomegalovirus: epidemiology and infection control.

Cytomegalovirus (CMV) causes asymptomatic infection in most individuals but can produce devastating illness in immunocompromised hosts and in a small proportion of congenitally infected babies. New techniques in molecular biology have provided insights into the epidemiology and transmission of CMV. Children in day care, their parents, and sexually active individuals, especially homosexual men, are now known to be at particular risk for acquiring CMV. Recent studies show that the risk of CMV acquisition by health care workers is similar to the risk to the general public. Health care workers should be aware of the wide range of clinical manifestations, methods of laboratory diagnosis, and current limitations of treatment of CMV. Careful handwashing and avoidance of excretions and secretions are recommended to decrease the transmission of CMV in the hospital.

Adult↗
PubMed1987

Treatment of varicella-zoster virus infections.

Effective antiviral therapy is now available for many forms of infection due to varicella-zoster virus. Acyclovir is the most widely prescribed treatment, but the virus is not exquisitely sensitive to this drug, and others are under study. The goals of therapy differ among different kinds of patients and must be considered when designing a treatment program.

Acyclovir↗