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Biomedical subjects

R B Craven

Publications and source records attributed to R B Craven.

At least 37 records · Page 2Linked to original sources

Studies of metabolic changes in cell cultures infected with four serotypes of dengue fever viruses by frequency-pulsed electron-capture gas-liquid chromatography.

Monkey kidney cell cultures were infected with four serotypes of dengue viruses, and the supernatant fluids of the cell cultures were extracted for amines, alcohols, carboxylic acids, and hydroxy acids. The derivatized extracts were then analyzed by frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC). FPEC-GLC profiles of the hydroxy acids showed peaks that were different for different serotypes and the FPEC-GLC carboxylic acid profiles differed from the control medium. These differences were reproducible when the same lot for medium was used. There were differences in profiles between lots of control media due apparently to different fetal bovine sera used in the growth medium. Therefore, the same lot of medium was necessary to reproduce profiles. The data obtained from the study indicate that FPEC-GLC can be used to detect changes in cellular metabolism caused by viral infection, and that these metabolic changes might be useful in detection of genetic differences in viruses as reflected by detectable changes in the metabolism of the infected cell.

Alcohols↗

Saturday night fever: a common-source outbreak of rubella among adults in Hawaii.

During the summer of 1977, an epidemic of rubella occurred among adults in Hawaii. The highest attack rate was in women 20-24 years old (226/100,000), with almost total sparing of young schoolchildren. A case-control investigation implicated a specific discotheque as a common place of exposure for persons with onset of disease during the epidemic peak (chi 2 = 12.9,p less than 0.001). A piano player/singer at the discotheque was the apparent source of the virus transmission. The large number of cases linked to this musician suggests that airborne transmission occurred while he was singing rather than by direct person-to-person contact. Rubella vaccine was given to 6523 women in public clinics held during the epidemic. Despite screening for pregnancy and birth control usage, 23 women (3.5/1000) became pregnant within three months after receiving the vaccine. Eleven of 12 women who reportedly contracted natural rubella while pregnant elected to terminate their pregnancies; the 12th had a normal appearing infant. The susceptibility rate for all adults tested for rubella hemagglutination inhibition antibody was 36.9%, a rate similar to the found in earlier surveys in Hawaii. The occurrence of this epidemic confirms the changing epidemiology of rubella with respect to age distribution and supports the view that vaccination of young children may not be sufficient to protect adult women from exposure to rubella, especially in areas where a high proportion of adults remain susceptible.

Adolescent↗

Gas chromatography in the identification of microorganisms and diagnosis of infectious diseases.

Gas-liquid chromatography (GLC) continues to find increasing applications in the characterization of microorganisms and the diseases associated with them. GLC has been used to characterize microorganisms through qualitative and quantitative analyses of cellular structural components and soluble extracts and metabolic by-products. Chromatographic patterns, or fingerprints, can be used to differentiate between very closely related microorganisms, even strain differences, and provides a potentially powerful tool for future taxonomic studies and more precision in definitive microbial classification. However, the most valuable use of GLC is in the identification of disease through patterns obtained by direct analysis of body fluids. Chromatographic fingerprints of microbial metabolites and compounds associated with the host response to infection and even noninfectious disease can be used to develop relatively simple GLC diagnostic methods. These methods are specific, sensitive, and rapid. This review examines the use of GLC for identification of infectious diseases through the analysis of body fluids, spent culture media, and cellular materials and suggest other clinical areas where its diagnostic potential has yet to be developed.

Bacterial Infections↗

Outbreak of influenza A/USSR/77 at Marquette University.

An outbreak of influenzalike illness occurred at Marquette University, Milwaukee, Wisconsin, in February 1978. Epidemiologic and laboratory data indicate that the outbreak was due to influenza A/USSR/77 (N1H1) virus. A self-administered questionnaire inquiring about the presence and spectrum of illness was given to faculty members, dental students, and residents of an undergraduate dormitory. Age-specific attack rates were 61.5% for persons less than or equal to 22 years of age, 24.7% for those 23 or 24 years of age, and 9.7% for those greater than or equal to 25 years of age. This pattern of age-specific attack rates paralleled the age distribution of persons without hemagglutination-inhibiting antibody to influenza A/USSR/77 virus found in independent serosurveys. Prior swine influenza (H1N1) immunization provided no protection from illness in this outbreak. Past epidemic antibody titers in undergraduates were only weakly associated with clinical illness. The data on disease impact gathered in this study indicate that in a university setting influenza A/USSR/77 virus produced a short-lived outbreak of respiratory illness with a very high attack rate in young adults.

Adolescent↗

Frequency-pulsed electron capture gas-liquid chromatography and the tryptophan color test for rapid diagnosis of tuberculous and other forms of lymphocytic meningitis.

A total of 260 samples of cerebrospinal fluid received from Egypt, the United States, Canada, and South America were examined by frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC) for tuberculous and other forms of lymphocytic meningitis. Thirty-four of the specimens were culture positive for M. tuberculosis, and four cerebrospinal fluid specimens of herpes meningitis were established by immunological techniques. The compound, 3-(2'-ketohexyl)-indoline, was found in about 60% of the Egyptian tuberculous specimens and none of the culture-positive American specimens. the carboxylic and hydroxy acid FPEC-GLC profiles were used effectively in conjunction with other clinical data to make the diagnosis even in the absence of 3-(2'-ketohexyl)indoline. Herpes meningitis and mixed infections of Myeobacterium tuberculosis-herpes, M. tuberculosis-leptospira, and M. tuberculosis-Haemophilus influenzae produced profiles different from each other and from pure culture cases. The color test for tuberculous meningitis was evaluated, and free tryptophan was eliminated as the source of color reaction. Indications are that 3-(2'-ketohexyl)indoline, in most cases, is not responsible for the positive color reaction. Differences in the clinical and FPEC-GLC data obtained from samples from different geographical regions are discussed.

Cerebrospinal Fluid↗

Limitations of the complement-fixation test for distinguishing naturally acquired from vaccine-induced yellow fever infection in flavivirus-hyperendemic areas.

On the basis of previous studies, it has long been stated that 17D yellow fever (YF) vaccine generally does not induce complement-fixing (CF) antibodies, and that the presence of CF antibodies could be used in epidemiological studies to distinguish individuals infected with wild YF virus from vaccinated persons. In January 1979, seroepidemiological investigations were conducted during a YF epidemic in The Gambia, West Africa. Since a mass vaccination campaign was also in progress, it was important to confirm that the CF test could be used for serodiagnosis and determination of the incidence of natural YF infections. The serological responses of 58 individuals who received 17D YF vaccine were studied. The vaccinees fell into three gorups: 1) those with prevaccination YF neutralizing (N) antibodies; 2) immunological virgins without prevaccination YF-N antibody or hemagglutination-inhibiting (HI) antibodies to heterologous flaviviruses (Zika, West Nile, dengue 1, Uganda S, Spondweni, or Ntaya; and 3) those without prevaccination YF-N antibodies but with heterologous flaviviral HI antibodies. Vaccination of persons without prior flaviviral immunological experience resulted in monotypic YF HI and/or N antibody seroconversions, but no CF antibody response. The presence of prevaccination YF N antibodies blocked serological response to the vaccine in a high proportion of the cases; however, 24% of vaccinees in this group had a marked rise in log2 YF CF antibody titer (mean increase of 3.9). Thirteen (46%) of 28 persons without prevaccination YF N, but with heterologous flaviviral HI antibodies demonstrated YF CF antibody seroconversion or increase in titer following vaccination; in this group the mean increase in log2/ YF CF antibody titer was 2.1. The CF antibody response was generally broadly cross-reactive; but in a few individuals, the YF CF antibody response was homotypic. Nine different patterns of HI and CF homologous and heterologous antibody responses were defined and are discussed. The practical significance of these studies is that they demonstrate that in a high percentage of persons with prior flavivirus exposure, anamnestic serological responses to YF vaccine result in CF antibodies similar to those induced by natural YF virus infection. In Africa and tropical America, where the background of flaviviral immunity is high, it is imperative that seroepidemiologic investigations during or after YF outbreaks be conducted prior to vaccination.

Adolescent↗

Yellow fever in the Gambia, 1978--1979: epidemiologic aspects with observations on the occurrence of orungo virus infections.

An epidemic of yellow fever (YF) occurred in the Gambia between May 1978 and January 1979. Retrospective case-finding methods and active surveillance led to the identification of 271 clinically suspected cases. A confirmatory or presumptive laboratory diagnosis was established in 94 cases. The earliest serologically documented case occurred in June 1978, at the extreme east of the Gambia. Small numbers of cases occurred in August and September. The epidemic peaked in October, and cases continued to occur at a diminishing rate through January, when a mass vaccination campaign was completed. The outbreak was largely confined to the eastern half of the country (MacCarthy Island and Upper River Divisions). In nine survey villages in this area (total population 1,531) the attack rate was 2.6--4.4%, with a mortality rate of 0.8%, and a case fatality rate of 19.4%. If these villages are representative of the total affected region, there may have been as many as 8,400 cases and 1,600 deaths during the outbreak. The disease incidence was highest in the 0- to 9-year age group (6.7%) and decreased with advancing age to 1.7% in persons over 40 years. Overall, 32.6% of survey village inhabitants had YF complement-fixing (CF) antibodies. The prevalence of antibody patterns indicating primary YF infection decreased with age, in concert with disease incidence. The overall inapparent:apparent infection ratio was 12:1. In persons with serological responses indicating flaviviral superinfection, the inapparent:apparent infection ratio was 10 times higher than in persons with primary YF infection. Sylvatic vectors of YF virus, principally Aedes furcifer-taylori and Ae. luteocephalus are believed to have been responsible for transmission, at least at the beginning of the outbreak. Eighty-four percent of wild monkeys shot in January 1979 had YF neutralizing antibodies, and 32% had CF antibodies. Domestic Aedes aegypti were absent or present at very low indices in many severely affected villages (see companion paper). In January, however, aegypti-borne YF 2.5 months into the dry season was documented by isolation of YF virus from a sick man and from this vector species in the absence of sylvatic vectors. Thus, in villages where the classical urban vector was abundant, interhuman transmission by Ae. aegypti occurred and continued into the dry season. A mass vaccination campaign, begun in December, was completed on 25 January, with over 95% coverage of the Gambian population. A seroconversion rate of 93% was determined in a group of vaccinees. This outbreak emphasizes the continuing public health importance of YF in West Africa and points out the need for inclusion of 17D YF vaccination in future programs of multiple immunication.

Adolescent↗

Development of a statewide program for surveillance and reporting of hospital-acquired infections.

In 1974, a statewide program was begun to improve surveillance of nosocomial infection in Virginia hospitals. Infection control practitioners were trained at the University of Virginia Hospital, Charlottesville, and were encouraged to submit monthly surveillance reports for analysis. In the first three years of the project, 141 students from 65 hospitals within the state attended a two-week basic course, with eight to 10 students per class. Of the 98 Virginia hospitals that sent students, 75 (73%) submitted monthly reports. The consistency of reporting (number of monthly reports received divided by the number of possible reporting months) was 83%. The sensitivity of reported data was estimated in comparative daily prospective surveys to be 69% for participating hospitals, and the specificity was 99%. The crude infection rate for the first 1.1 million patients at risk was 3.3%.

Cross Infection↗

The Russian flu. Its history and implications for this year's influenza season.

From November 1977 through mid-January 1978 the population younger than 25 years in the Union of Soviet Socialist Republics experienced a widespread epidemic of mild influenza (Russian flu) caused by an H1N1 virus similar to the virus that circulated worldwide during the early 1950s. Outbreaks of Russian flu occurred in school populations and military recruits in the United States starting in mid-January. Many other countries reported outbreaks of H1N1 virus in the winter of 1978. Predictions of influenza activity are always hazardous, but most experts believe that the Russian flu may occur again in the fall and winter of 1978. Other type A and B strains may also circulate; therefore, a trivalent vaccine containing A/USSR, A/Texas, and B/Hong Kong virus strains will be available. It is recommended that the chronically ill and those 65 years and older be the target populations for annual vaccination.

Adolescent↗

Possible use of frequency-pulse-modulated electron capture gas-liquid chromatography to identify septic and aseptic causes of pleural effusions.

Frequency-pulse-modulated electron capture gas-liquid chromatography was used in conjunction with appropriate derivatization procedures to obtain chromatograms from extracts of pleural effusions. These chromatograms were used to rapidly classify the various types of pleural effusions. With this method we have been able to distinguish among a limited number of effusions caused by congestive heart failure, Mycobacterium tuberculosis, and some other types of bacterial empyemas and pleural effusions.

Chromatography, Gas↗

Protective efficacy of an inactivated Mycoplasma pneumoniae vaccine.

The protective efficacy of a formalin-inactivated Mycoplasma pneumoniae vaccine was evaluated in a double-blind fashion in 7,861 Marine Corps recruits at Parris Island, South Carolina. Vaccine, administered in a 1-ml dose by a jet-injection device, was glass-grown and contained 264 microgram of protein nitrogen/ml. Phosphate-buffered saline with formalin was injected as a control. Systemic reactions to injection were similar in both groups, but the percentage of vaccinees with erythema (51%) and induration (52%) at 24 hr was significantly greater than the percentage of controls (2%) with these reaction (P less than 0.001). Twenty-one (0.5%) of 3,930 vaccinees and 43 (1.1%) of the 3.931 placebo recipients were hospitalized with pneumonia (chi2=7.61; P less than 0.01). Ten of 21 vaccinees and seven of 43 controls with pneumonia had a positive pharyngeal culture for M. pneumoniae (chi2=1.69; P =0.20), and fourfold rises in titer of serum antibody were noted in five of 14 vaccinees and in 15 of 28 placebo recipients with pneumonia (chi2=7.90; P less 0.0005). Therefore, vaccine efficacy for M. pneumoniae-specific pneumonia was 42% as determined by cultures and 67% by serologic tests. The vaccine showed no protective efficacy for M. pneumoniae-specific bronchitis or for M. pneumoniae pharyngeal carriage in recrutis in training.

Antibodies, Bacterial↗

Electron capture gas chromatography detection and mass spectrum identification of 3-(2'-ketohexyl)indoline in spinal fluids of patients with tuberculous meningitis.

A basic, extractable, indolic type of compound, which was derivatized with heptafluorobutyric anhydride and pyridine, was obtained from the cerebrospinal fluids of patients with acute tuberculous meningitis. The compound was detected by frequency-pulsed, modulated electron capture gas-liquid chromatography, and it was tentatively identified by mass spectrometry as 3-(2'-ketohexyl)indoline. The compound was found to be valuable for differentiating between tuberculous, cryptococcal, and aseptic meningitides.

Chemical Phenomena↗

Rapid diagnosis of lymphocytic meningitis by frequency-pulsed electron capture gas-liquid chromatography: differentiation of tuberculous, cryptococcal, and viral meningitis.

Cerebrospinal fluid specimens from patients with tuberculous (17 cases), cryptococcal (15 cases), and viral (14 cases) meningitis were analyzed by frequency-pulsed electron capture gas-liquid chromatography and mass spectrometry. Compounds that disappeared after therapy were found to be present in each of these specimens and were not detected in controls. They occurred in repetitive patterns such that these three types of meningitis could be rapidly distinguished. The compound associated with tuberculous meningitis has been tentatively identified. These finding have implications for rapid diagnosis, pathophysiological studies, and possible new therapeutic approaches.

Chromatography, Gas↗

Field trial of an inactivated Mycoplasma pneumoniae vaccine. I. Vaccine efficacy.

The efficacy of an inactivated Mycoplasma pneumoniae vaccine was evaluated in a double-blind study of 7,861 Marine Corps recruits at Parris Island, South Carolina. Vaccine was administered to half for the volunteers in a 1-ml dose by a jet-injection device, and phosphate-buffered saline was administered similarly to control subjects. Twenty-one vaccinees (5.3 per 1,000) and 43 recipients of placebo (10.9 per 1,000) were hospitalized with pneumonia; the incidence of illness among the two groups indicated a 51% overall protective efficacy for the vaccine (x2 = 7.49; P less than 0.01). The refined data for pneumonia due to M. pneumoniae showed 67% protective efficacy when serologic data were employed (x2 = 7.84; P = 0.005) and a 42% protective efficacy (x2 = 1.80; P greater than 0.10) when data from cultures for M. pneumoniae were employed. Vaccinees with pneumonia due to M. pneumoniae suffered no increased illness compared to controls, suggesting no hypersensitization with natural illness following the inactivated vaccine. Only when serologic data were analyzed did it appear that the M. pneumoniae vaccine protected against M. pneumoniae specific bronchitis (35% efficacy) but the difference was not statistically significant (x2 = 1.28; P greater than 0.20).

Bacterial Vaccines↗

Comparison of the sensitivity of two methods for isolation of Mycoplasma pneumoniae.

Throat swab specimens from 1,494 Marine Corps recruits were inoculated into vials containing diphasic (broth/agar) mycoplasma medium and also onto PPLO agar plates, which were subsequently overlayed with sheep erythrocytes in saline agar. Strains of Mycoplasma pneumoniae were isolated from 89 (6%) of the specimens by one or both of the methods. Eight-one of the 89 (91%) positive specimens were cultured with diphasic medium, whereas only 42 (47%) were cultured with the overlay method (x2 = 7.44, P less than 0.01). The diphasic system for isolation of M. pneumoniae should be the method of choice in clinical and research application.

Adult↗

Minimizing tuberculosis risk to hospital personnel and students exposed to unsuspected disease.

A 15-month prospective study of the personnel and students exposed to initially unsuspected active cases of tuberculosis was undertaken to define the risk of their acquiring infection. Eight of 484 (1.65%) personnel exposed to 17 initially unsuspected tuberculosis patients and 5 of 2013 (0.25%) unexposed personnel with similar risk but no known exposures developed positive tuberculin skin tests. This greater than sixfold increase in conversion rate for the exposed group was significant (chi-2=14.83; P=0.0003). Delay in making the diagnosis in these patients was associated with failure to apply a tuberculin skin test on admission in 14 patients and radiologic misinterpretation in 15. A comprehensive surveillance method involving the Employee and Student Health Departments as well as the Public Health Department is suggested to minimize the risk of undiagnosed tuberculosis.

Cross Infection↗