Biomedical subjects

R L Atmar

Publications and source records attributed to R L Atmar.

At least 55 records · Page 3Linked to original sources

PubMed1996

Comparison of reverse transcription-PCR with tissue culture and other rapid diagnostic assays for detection of type A influenza virus.

We applied a reverse transcription (RT)-PCR assay for influenza A virus to combined nasal wash-throat swab specimens previously obtained from an outpatient pediatric population with acute respiratory illness during concurrent epidemics of influenza A virus and respiratory syncytial virus. The results of the RT-PCR assay were compared with those previously reported with virus cultivation and commercially available rapid diagnostic kits (E.A. Dominguez, L.H. Taber, and R.B. Couch, J. Clin. Microbiol. 31:2286-2290, 1993). With virus cultivation as the "gold standard", the RT-PCR assay had a sensitivity, specificity, and efficiency of 95, 98, and 97%, respectively, compared with 75, 100, and 93%, respectively, for the best diagnostic kit (Becton Dickinson Directigen). RT-PCR is an effective alternative to virus isolation for the detection of influenza A virus in clinical specimens.

Child↗

PubMed1995

Comparison of trivalent cold-adapted recombinant (CR) influenza virus vaccine with monovalent CR vaccines in healthy unselected adults.

A trivalent cold-adapted recombinant (CR) influenza virus vaccine containing types A and B viruses was compared with monovalent vaccines of each virus in a double-blind, placebo-controlled trial. Adults with a wide range of preexisting antibody titers received one 0.5-mL dose intranasally of trivalent vaccine; monovalent A/H1N1, A/H3N2, or B vaccine; or placebo. All vaccines were well tolerated. Serum antibody response frequencies and postvaccination geometric mean antibody titers were similar for recipients of trivalent or the corresponding monovalent vaccine for each of the vaccine components. Stepwise logistic regression analysis of the antibody responses of trivalent vaccine recipients demonstrated that response to one vaccine virus did not adversely affect the likelihood of response to the other viruses. This study failed to find serologic evidence of interference between vaccine viruses, suggesting that trivalent CR influenza virus vaccine may be useful for preventing influenza in adult populations.

Acclimatization↗

PubMed1995

Detection of Norwalk virus and hepatitis A virus in shellfish tissues with the PCR.

A method for the detection of Norwalk virus and hepatitis A virus from shellfish tissues by PCR was developed. Virus was added to the stomach and hepatopancreatic tissues of oysters or hard-shell clams, and viral nucleic acids were purified by a modification of a previously described method (R.L. Atmar, T.G. Metcalf, F.H. Neill, and M.K. Estes, Appl. Environ. Microbiol. 59:631-635, 1993). The new method had the following advantages compared with the previously described method: (i) more rapid sample processing; (ii) increased test sensitivity; (iii) decreased sample-associated interference with reverse transcription-PCR; and (iv) use of chloroform-butanol in place of the chlorofluorocarbon trichlorotrifluoroethane. In addition, internal standards for both Norwalk virus and hepatitis A virus were made which demonstrated when inhibitors to reverse transcription-PCR were present and allowed quantitation of the viral nucleic acids present in samples. This assay can be used to investigate shellfish-associated gastroenteritis outbreaks and to study factors involved in virus persistence in shellfish.

Animals↗

PubMed1994

In situ detection of hepatitis A virus in cell cultures and shellfish tissues.

An in situ transcription method was developed to detect hepatitis A virus RNA in both cell cultures and shellfish tissues. Radiolabeled cDNA copies were synthesized in situ by reverse transcriptase-directed transcription after annealing with a specific primer to the viral RNA. Both tritium (3H) and 35S were useful in the in situ transcription reaction, but the use of 3H resulted in a lower background and finer detail in the localization of viral particles. Application of the method to different organs of oysters which had bioaccumulated hepatitis A virus allowed the first in situ localization of the virus, specifically in stomach and hepatopancreatic tissues.

Animals↗

PubMed1994

Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness.

Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.

Acute Disease↗

PubMed1994

High doses of purified influenza A virus hemagglutinin significantly augment serum and nasal secretion antibody responses in healthy young adults.

The reactogenicity and immunogenicity of purified influenza virus hemagglutinin (HA) vaccines administered intramuscularly were evaluated in two placebo-controlled clinical trials. A total of 139 healthy young adults were randomized to receive increasing doses of monovalent influenza A/Taiwan/1/86 (H1N1) virus HA (range, 0 to 405 micrograms per dose [study 1]). An additional 139 subjects were given increasing doses of a trivalent HA vaccine containing equal amounts of A/H1N1 virus, A/Shanghai/16/89 (H3N2) virus, and influenza B/Yamagata/16/88 virus HA (range, 0 to 135 micrograms of HA per strain, 0 to 405 micrograms per dose) or a standard dose of commercial influenza vaccine (study 2). Increasing doses of HA were associated with increasing frequencies of symptoms at the vaccination site early after vaccination, but all doses were well tolerated. Occurrence of systemic symptoms was unrelated to dose. Increasing the dose of HA resulted in increasingly higher postimmunization levels of serum hemagglutination inhibiting and neutralizing antibody levels versus influenza A/H1N1 virus in study 1 (P < 0.05); these enhanced responses persisted for up to 6 months. Nasal secretory immunoglobulin A and G antibody responses were assessed 2 weeks after immunization with monovalent H1N1 virus HA; the frequencies of significant responses also increased in a dose-related fashion. Similar increases in serum antibody levels were noted for both A/H1N1 and A/H3N2 viruses in study 2. These data provide a basis for proceeding with the evaluation of high doses of purified HA in the elderly.

Adolescent↗

PubMed1993

Detection of enteric viruses in oysters by using the polymerase chain reaction.

A procedure for the detection of enteric viral nucleic acid in oysters by the polymerase chain reaction was developed. Known quantities of poliovirus type 1 were seeded into oysters. Virus was extracted and concentrated by using organic flocculation and polyethylene glycol precipitation. Inhibitors of reverse transcription-polymerase chain reaction were present in the oyster extracts, preventing amplification of target viral nucleic acid. The use of cetyltrimethylammonium bromide precipitation sufficiently removed inhibitors to allow detection of as few as 10 PFU of poliovirus. Norwalk virus also could be detected after being seeded into oysters. This methodology may be useful for the detection of these and other shellfish-borne viral pathogens.

Animals↗

PubMed1993

Classification of respiratory tract picornavirus isolates as enteroviruses or rhinoviruses by using reverse transcription-polymerase chain reaction.

The classification of picornaviruses isolated from respiratory secretions as human rhinoviruses (HRVs) or enteroviruses (EVs) by using reverse transcription-polymerase chain reaction was compared to that derived from acid lability testing. Of the 135 clinical isolates examined, 91 were found to be HRVs and 44 were EVs. There was 100% concordance between the two classification methods. Reverse transcription-polymerase chain reaction is an effective alternative to traditional methods for differentiating HRVs from EVs.

Base Sequence↗

PubMed1992

Complications of measles during pregnancy.

Twelve pregnant women and one woman who had just given birth were hospitalized with measles in Houston between 1988 and 1990. The most common and serious maternal complication was pneumonitis (seven patients). Other maternal complications included hepatitis (seven patients), premature labor (four patients), spontaneous abortion (one patient), and death (one patient). For four of 13 patients, all of whom had severe measles and pneumonitis due to measles virus, an adverse fetal outcome such as abortion or prematurity was associated with their conditions. Historical accounts describing maternal sequelae of measles have suggested more severe disease in pregnant women, although this observation has not always been confirmed by more recent reports in developed countries. The clinical course in our patients suggests that measles during pregnancy may be associated with serious complications.

Abortion, Spontaneous↗

PubMed1992

Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection.

Bacterial infections are a well-described complication of AIDS. However, relatively few reports have described infections due to Pseudomonas aeruginosa in adults who are infected with the human immunodeficiency virus (HIV). Seven cases of serious P. aeruginosa infection in HIV-infected patients occurred during 12 months in two hospitals in Houston, often in the absence of other host factors that are generally thought to predispose to this condition. One patient had no prior illness or antibody test results that were suggestive of HIV infection; for two other patients who were known to have antibody to HIV, an AIDS-defining diagnosis had never been made. Three patients had pneumonia (two with bacteremia and one with empyema), one had malignant otitis externa, and three had bacteremia that either resulted from or caused secondarily a soft-tissue focus of infection. Two patients died, and two others experienced one or more relapses after an initial course of treatment. Compromised host defense mechanisms, including loss of mucosal integrity, defects in humoral and cellular immunities, and qualitative or quantitative leukocyte abnormalities, may predispose HIV-infected patients to P. aeruginosa infections.

Acquired Immunodeficiency Syndrome↗

PubMed1992

B-cell activation and differentiation by HIV-1 antigens among volunteers vaccinated with VaxSyn HIV-1.

The generation of memory B cells in response to vaccination with a baculovirus-derived recombinant gp160 candidate AIDS vaccine, VaxSyn HIV-1, was investigated in 12 healthy human volunteers who were immunized with VaxSyn HIV-1, hepatitis B vaccine, or alum adjuvant alone on days 1, 28, 180, and 540. Peripheral blood mononuclear cells were collected pre- and post-immunization and cultured unstimulated or with pokeweed mitogen (PWM), VaxSyn HIV-1 (rgp160), or HIV-1 lysate (iHIV-1) for 7 days before polyclonal and HIV-1-specific IgG production in culture supernatants (SNs) were measured. No differences were seen in the spontaneous or PWM-induced IgG production in SN from vaccinees and controls. Only vaccinee SN contained higher-than-normal levels of polyclonal IgG after stimulation with either rgp160 or iHIV-1, especially after the second and third booster immunizations on days 180 and 540, respectively. There were also contemporaneous increases in HIV-1-specific antibody in SN of all vaccinees, albeit at different time points throughout the study. We conclude that VaxSyn HIV-1 induces antigen-specific B-cell responses with the generation of memory B cells in vivo that can be reactivated in vitro to deliver an anamnestic response.

AIDS Vaccines↗

PubMed1991

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network.

OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans. SUBJECTS: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups. INTERVENTIONS: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540. MEASUREMENTS AND MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time. CONCLUSIONS: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.

Adult↗

PubMed1990

Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults.

The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults.

Adolescent↗

PubMed1990

Safety and pharmacokinetics of rimantadine small-particle aerosol.

The safety and pharmacokinetics of rimantadine administered by small-particle aerosol were assessed in healthy adults and adults with acute influenza virus infection. Aerosolized rimantadine delivered at a concentration of 40 micrograms/liter of air was associated with nasal burning and irritation in normal volunteers. A concentration of 20 micrograms/liter of air was well tolerated for up to 12 h by normal volunteers and was not associated with any changes in pulmonary function, as measured by routine spirometry, plethysmography, or diffusion capacity of carbon monoxide. Mean peak levels of drug in serum were approximately 10-fold lower after 12 h of aerosol administration than they were after oral administration of 200 mg (29.7 versus 255 ng/ml, respectively), while mean nasal wash levels were approximately 100-fold higher (6,650 versus 66.6 ng/ml, respectively). Elimination half-lives were similar after both aerosol and oral administration (24.1 and 25.2 h, respectively), and rimantadine urinary excretion was less than 1% per 24 h in both groups. Twenty micrograms of aerosolized rimantadine per liter of air given 12 h daily for 3 days to nine adults with acute influenza virus infection was well tolerated. Levels in plasma after 12 h of aerosol inhalation were similar to those in normal volunteers, but were higher at the end of the third treatment than they were at the end of the first treatment (88.3 versus 47.9 ng/ml, respectively). Thus, rimantadine delivered via small-particle aerosol at a dose of 20 micrograms/liter of air was well tolerated in normal volunteers and in those with acute influenza and was associated with high local concentrations.

Adult↗

PubMed1989

Pneumonia caused by Mycoplasma pneumoniae and the TWAR agent.

Mycoplasma pneumoniae and the TWAR agent account for a good proportion of pneumonias acquired in the community among older children and young adults. Recovery from these infections is common, although serious complications may occur. Each is associated with fever, nonproductive cough, and headache. The full clinical manifestations of TWAR agent infection are only now beginning to be defined. Diagnosis of M pneumoniae can be by serology and/or culture capabilities. The TWAR agent cannot be routinely isolated and serologic tests are available only in research laboratories. Response to tetracycline antibiotics has been established for each agent and hospitalization is rarely needed. Erythromycin and other macrolide antibiotics have good activity against M pneumoniae and can be employed as an alternative to tetracycline antibiotics for this pathogen.

Adult↗

PubMed1987

Effect of BMY-28100, a new cephalosporin, on Staphylococcus aureus nasal carriage.

In order to examine the in vivo activity of BMY-28100, serial quantitative nasal cultures were taken from 52 nasal carriers of Staphylococcus aureus following administration of the antimicrobial. Nasal carriage rates and mean log titers decreased significantly during (days 2-4 and 5-8) and following (days 1-2 and 6-7) treatment. No change in antibiotic sensitivities was noted in follow-up isolates, and the MIC90 remained at 2mcg/ml. BMY-28100 demonstrated good in vivo activity against Staphylococcus aureus.

Adult↗

PubMed1983

Ribavirin aerosol treatment of influenza B virus infection.

In a randomized, controlled study, ribavirin small particle aerosol was found to be effective in the treatment of influenza B virus infection in a group of college students. Eleven treated patients experienced significantly more rapid defervescence, disappearance of systemic illness, and reduction of virus shedding in nasal secretions than 10 control patients treated with a saline aerosol. Antibody response to infection was similar in both groups. The treatment was well tolerated and hematologic and clinical chemical tests revealed no toxicity. The estimated dose of ribavirin aerosol retained was about 2 g in 35.5 hr of treatment during the first 60 hr in the hospital.

Adult↗

PubMed1983

Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants.

In a double-blind study, bronchiolitis associated with respiratory syncytial virus infection in 12 randomly selected patients treated with ribavirin aerosol improved more rapidly than in 14 control patients given saline aerosol (P = .044, Wilcoxon rank sum test, two-tailed). An estimated 10 mg of ribavirin per kilogram of body weight was administered in daily 12-hour treatments over a five-day period. Respiratory syncytial virus disappeared from secretions at about the same rate in treated and control patients. There was no local or systemic intolerance, and there was no evidence of hematologic or other organ toxicity in the ribavirin-treated patients.

Aerosols↗