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Biomedical subjects

M H Sawyer

Publications and source records attributed to M H Sawyer.

At least 19 recordsLinked to original sources
PubMed2001

Enterovirus infections: diagnosis and treatment.

Enterovirus infections are common in both children and adults and range from benign short-lived febrile illnesses to life-threatening infections. Recent developments in nucleic acid amplification techniques now allow the rapid and sensitive diagnosis of enterovirus infections, which in turn can lead to improvements in patient management that shorten hospitalizations and reduce costs. New antiviral drugs have been developed that inhibit enterovirus replication, and early clinical trials of these compounds suggest that effective therapy for enterovirus infections is now possible.

Adolescent↗
PubMed1998

Evaluation of PCR assays in presence of antibody to thermostable DNA polymerases for detection of microbial agents: avoiding false negative results for specimen containing low-titer agent.

The serial low-titer specimens of Influenza A virus and Adeno virus type 7 were tested for the presence of virus specific genes by PCR based on Tth DNA polymerase and by that based on Taq DNA polymerase, in the absence and presence of antibody to the respective DNA polymerases. Increased product DNA synthesis and higher sensitivity of detection were observed in the presence of antibody compared to those in the absence of antibody. 10- to 100- fold lower titer specimen of Influenza A virus and 10-fold lower titer specimen of Adeno virus could be detected in the presence of antibody than those detected in the absence of antibody to the appropriate DNA polymerase, in a PCR.

Adenoviruses, Human↗
PubMed1998

Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease.

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.

Administration, Oral↗
PubMed1998

Detection of Bordetella pertussis and respiratory synctial virus in air samples from hospital rooms.

OBJECTIVE: To evaluate the distribution of Bordetella pertussis and respiratory syncytial virus (RSV) in the hospital setting. DESIGN: Air samples were collected using filters in the hospital rooms of 12 children with pertussis and 27 children with RSV infection. Material eluted from these filters was subjected to RSV- and B pertussis-specific polymerase chain reaction (PCR) amplification. SETTING: Patients were hospitalized in private rooms in one of two referral centers, a university teaching hospital and a university-affiliated private children's hospital. PATIENTS: 12 children (16 days-3 years of age) with documented pertussis infection and 27 patients (10 days-7 years of age) with documented RSV infection. RESULTS: B pertussis DNA was detected in 7 (58%) of 12 rooms housing pertussis patients and in 16 (25%) of 63 total samples. B pertussis DNA was detected as far as 4 m away from the patient's bedside. The detection of B pertussis DNA in air samples did not change over the short duration of hospitalization. RSV RNA was detected in 17 (63%) of 27 rooms housing RSV-infected patients and in 32 (22%) of 143 total samples. RSV RNA was detected at distances as far as 7 m from the patient's bedside and for up to 7 days of hospitalization. CONCLUSIONS: Using PCR-based detection methods, B pertussis DNA and RSV RNA both can be detected in air samples from the hospital rooms of infected patients. Both can be detected at large distances from a patient's bedside in a minority of cases. These detection methods are suitable for further studies of control measures used to contain nosocomial infections caused by both B pertussis and RSV.

Air Microbiology↗
PubMed1998

Effect of inhibitors in clinical specimens on Taq and Tth DNA polymerase-based PCR amplification of influenza A virus.

Fifteen randomly selected nasopharyngeal (NP) swab specimens (culture-negative for influenza A virus) were spiked with influenza A virus and the nucleic acids were extracted and subjected to PCR amplification with Thermus aquaticus (Taq) and T. thermophilus (Tth) DNA polymerases. Products of the expected size, and giving equivalent band intensities, were obtained from four specimens with both polymerases. Fox six specimens, less products were obtained with Taq DNA polymerase than with Tth DNA polymerase. Products were detected from five NPs only by PCR with Tth DNA polymerase. The transport medium and the calcium alginate swab fibre of the specimens were shown not to be the source of the inhibitors. The incorporation of 32P-dCTP into cDNA, and the yield of PCR products of cDNA made from control RNA template (purified from H2O spiked virus suspension) were decreased in the presence of inhibitory extracts, showing that both the reverse transcription (RT) and PCR steps in amplification with Taq DNA polymerase were sensitive to the inhibitors. In contrast, Tth DNA polymerase was more resistant to the inhibitors and viral nucleic acid from all the specimens examined could be amplified and detected in a single step by RT-PCR with Tth DNA polymerase.

DNA, Complementary↗
PubMed1997

Reliability of a history of previous varicella infection in adults.

CONTEXT: Apparent second episodes of varicella are reported in immunocompetent hosts, but laboratory confirmation of prior immune status has rarely been possible. OBJECTIVE: To evaluate adult patients with varicella who claimed to have had previous varicella to determine whether they had true second episodes or primary cases with inaccurate clinical histories. DESIGN: Adult subjects with varicella who enrolled in an antiviral treatment trial were interviewed about a history of varicella. The clinical course of varicella was documented prospectively in all subjects. Serum samples that predated the acute illness were obtained from the US Navy's central serum storage facility for subjects who reported a previous episode of varicella. These stored samples were tested in parallel by enzyme-linked immunosorbent assay, latex agglutination, and Western blot for IgG antibodies to varicella-zoster virus (VZV). PARTICIPANTS: Twenty military personnel with varicella and a history of the disease. SETTING: A military hospital in San Diego, Calif. MAIN OUTCOME MEASURE: Presence or absence of antibodies to VZV. RESULTS: Twenty (10.8%) of 184 adults with serologically confirmed acute varicella reported a prior history of varicella. The clinical course of these 20 patients did not differ from those with no history of varicella. Serum samples that had been collected a mean of 12.4 months (median, 12 months; range, 3 days to 34 months) before the incident episode were available for 19 subjects. All 19 serum samples lacked IgG antibodies to VZV. CONCLUSION: A history of previous varicella infection in adults with varicella may not be reliable. True second episodes of varicella are probably rare in immunocompetent adults.

Adult↗
PubMed1997

Optimized PCR amplification of influenza A virus RNA using Tth DNA polymerase, incorporating uracil N glycosylase (UNG) in a single tube reaction.

An optimized reaction condition for amplification of influenza A virus RNA, by thermus thermophilus (Tth) DNA polymerase-based PCR, incorporating uracil N glycosylase (UNG) and dUTP in the reaction has been determined. dUTP could not be substituted for all dTTP sites when UNG was present in the reaction. The relative concentration of dUTP and dTTP has been optimized for allowing amplification of the target RNA. It has been verified that the amplified product DNA had sufficient dUTP and was digestable by UNG. Using the optimized reaction condition, influenza A virus-specific DNA fragment could be amplified and detected in 15 of 15 culture positive (for influenza A virus) nasopharyngeal specimens.

DNA Glycosylases↗
PubMed1997

Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. The MMRV Study Group.

OBJECTIVE: To determine the safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. DESIGN: Healthy children, 12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. SUBJECTS: The study group included 294 healthy children, ages 12 to 18 months, with a negative history of measles, mumps, rubella and varicella. MAIN OUTCOME MEASURES: The seroconversion rate and magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R II and PedvaxHIB. RESULTS: Healthy children, 12 to 18 months of age, who received MMRV and PedvaxHIB concurrently showed immune responses similar to those in the control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6 weeks later. Antibody titers for varicella were significantly lower when MMRV was administered than when varicella vaccine was given separately (0.712-fold difference, P = 0.028). No vaccine-related serious adverse reactions were reported, and no clinically significant differences were seen in the safety profiles of the two treatment groups. CONCLUSIONS: There were no statistically significant differences in the seroconversion rates between the two treatment groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower geometric mean titers for varicella were noted in the group who received MMRV compared to VARIVAX given alone. Six-week seroconversion rates, persistence of immune responses at 1 year and the frequency of local and systemic reactions were comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and PedvaxHIB followed by VARIVAX 6 weeks later.

Antibodies, Viral↗
PubMed1996

Treatment of adult varicella with sorivudine: a randomized, placebo-controlled trial.

The antiviral and clinical efficacy of sorivudine in adults with varicella was evaluated in a double-blind, placebo-controlled randomized trial. A total of 186 patients were hospitalized for isolation and treatment within 96 h of rash onset. The diagnosis of varicella was confirmed in 184 patients with paired sera. Patients were randomly assigned to receive 10 or 40 mg of sorivudine or an identical placebo once a day for 5 days. Treatment with 40 mg of sorivudine (compared with placebo) shortened the mean time to 100% crusting from 6.6 to 5.8 days (P = .004) and reduced the mean days that new lesion formed from 3.9 to 3.1 (P = .014). Mean days of cutaneous viral shedding were reduced from 3.3 in the placebo group to 2.6 in the 40-mg sorivudine group (P = .002). The effectiveness of therapy was not affected by the duration of rash before initiation of therapy. Sorivudine is a promising new agent for the treatment of varicella-zoster virus infections.

Administration, Oral↗
PubMed1995

Rapidly recurrent enteroviral meningitis in non-immunocompromised infants caused by different viral strains.

Repeated episodes of enteroviral meningitis occurring within a 1-month period in two non-immunocompromised infants were investigated using molecular techniques to distinguish persistent or recrudescent infection from new infection. Viral RNA from cerebrospinal fluid was amplified by polymerase chain reaction, cloned, and the nucleic acid sequences determined. This analysis demonstrated that both infants had recurrent episodes of meningitis caused by new infection with a distinct enterovirus strain. The molecular methods that were employed should prove useful in similar clinical settings as well as for the study of enteroviral outbreaks. These cases also illustrate the potential for rapid reinfection of infants with different viruses of the same genus.

Base Sequence↗
PubMed1995

Rhabdomyolysis associated with acute varicella infection.

We report two cases of intense, generalized rhabdomyolysis complicating varicella-zoster virus (VZV) infections, one in an adolescent and one in a young adult male. In both cases, myoglobinuria and weakness of large muscle groups developed within 5 days of the onset of vesicular lesions. A muscle biopsy from one of the individuals showed muscle fiber necrosis in the absence of acute inflammatory infiltrates or vasculitis. Culture of the muscle biopsy specimen for VZV was negative; however, the VZV genome was detected by the polymerase chain reaction. Both patients recovered fully after treatment with hydration therapy alone.

Acute Disease↗
PubMed1994

Detection of varicella-zoster virus DNA in air samples from hospital rooms.

Varicella-zoster virus (VZV) is a highly contagious infectious agent that causes outbreaks in institutional settings. Transmission of VZV is felt to occur following direct contact with an infected individual and by aerosol spread. To document the aerosolization of VZV, a polymerase chain reaction (PCR) assay was used to detect VZV DNA in air samples obtained from hospital rooms of patients with active VZV infection. VZV DNA was detected in 64 (82%) of 78 air samples from rooms housing patients with active varicella and 9(70%) of 13 samples from rooms of patients with herpes zoster. VZV was detected 1.2-5.5 m from patients' beds and for 1-6 days following onset of rash. On some occasions, VZV DNA could be detected outside the hospital isolation rooms housing patients. This PCR-based method allows the detection and semiquantitation of VZV aerosolization and can be a useful tool for monitoring efforts to control VZV aerosols in the environment.

Adolescent↗
PubMed1994

Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak.

Enteroviruses are common causes of localized and systemic infection in patients of all ages and are the most frequent cause of epidemic aseptic meningitis in the United States. We have developed a polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) for rapid diagnosis of enteroviral meningitis. This assay was applied to 257 CSF specimens during a large community outbreak of enterovirus disease; 109 (97%) of 112 enterovirus culture-positive CSF samples contained enterovirus RNA. In addition 35 (66%) of 53 samples from patients with suspected central nervous system disease with negative or no CSF viral cultures were positive by enterovirus PCR. The enterovirus PCR detected 13 different enterovirus serotypes. PCR results are available within 24 hours compared with a mean of 6.8 days for enterovirus culture. The clinical characteristics of 141 patients with enterovirus central nervous system disease are presented. This study demonstrates the usefulness of enterovirus PCR for the rapid diagnosis of enterovirus central nervous system disease and the potential for PCR tests to shorten hospitalization.

Base Sequence↗
PubMed1994

Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay.

A 5-h, user-friendly PCR assay for the diagnosis of enteroviral meningitis was developed. Reverse transcription and amplification were performed in a one-step reaction using rTth polymerase. Carryover contamination was prevented with dUTP and uracil N-glycosylate. Detection was performed colorimetrically on a microwell titer plate. Sensitivity, specificity, positive predictive value, and negative predictive value were 94.7, 97.4, 94.7, and 97.4%, respectively.

Base Sequence↗
PubMed1994

Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management.

STUDY OBJECTIVE: To evaluate the performance characteristics and potential clinical utility of a polymerase chain reaction (PCR) assay for enteroviral RNA in comparison to viral culture in infants under 3 months of age with meningitis. SPECIMENS AND TESTING: Specimens were obtained from a collection of cerebrospinal fluid specimens from infants under 3 months of age (excluding those in the neonatal intensive care unit) undergoing lumbar puncture at St. Louis Children's Hospital during a 12-month period. Those tested by PCR included all 27 with pleocytosis, 8 others from infants without pleocytosis but from whom an enterovirus was cultured, and 10 from infants who did not have pleocytosis and had a negative viral culture of cerebrospinal fluid. Viral cultures were performed at the discretion of physicians caring for individual patients. RESULTS: PCR was positive for enteroviral RNA on cerebrospinal fluid (CSF) specimens from 11 of 12 patients with definite or probable enteroviral meningitis, as well as on 6 of 13 with possible enteroviral meningitis, and was negative on all 10 with absence of pleocytosis and negative enteroviral cultures. CSF viral cultures were negative in 6 of the patients in whom PCR was positive. Viral cultures had minimal impact on patient management. In contrast, under study assumptions, PCR could have saved an average of 1.2 days of hospitalization per patient in the 27 patients with CSF pleocytosis. CONCLUSIONS: Enterovirus PCR performed on CSF is a sensitive and specific method for the diagnosis of enteroviral meningitis. This method has the potential for improving the accuracy of diagnosis in young infants and for saving costs by allowing earlier diagnosis and discharge from the hospital when clinically appropriate.

Cerebrospinal Fluid↗