Biomedical subjects
W Schaffner
Publications and source records attributed to W Schaffner.
Outbreak of acute pulmonary histoplasmosis in members of a wagon train.
In August 1980, an outbreak of acute pulmonary histoplasmosis occurred among participants in a wagon train as it traveled through eastern Tennessee. Of the 85 people on the train 69 (81 percent) had evidence of infection with Histoplasma capsulatum. Fifty-four people had symptomatic disease. The source of infection was traced to the site of a former winter blackbird roost in Charleston, Tennessee, that had been partially cleared five years earlier to make a park. Fourteen of 25 soil samples from this site were culture-positive for H. capsulatum. This is the first reported outbreak to involve a large migrant group. The outbreak is unusual in that exposure occurred without excavation, construction or tree-cutting at the site.
Evolution of antimicrobial resistance and nosocomial infection. Lessons from the Vanderbilt experience.
The development of antimicrobial resistance by bacteria has had profound effects of the clinical use of antibiotics, especially in hospital-acquired infections. In 1973, a large outbreak of nosocomial infections due to Serratia marcescens began at the Vanderbilt University medical complex, a major characteristic of which was high-level resistance to gentamicin and carbenicillin. Investigation of the outbreak and subsequent in vitro studies have shown that the evolution and epidemiology of this high-level resistance operated at three levels of organizations: (1) dissemination of individual strains, (2) dissemination of a plasmid among different strains and (3) movement of a discrete genetic element, or transposon, between plasmids. The investigations of this outbreak and other studies reviewed support the concept that resistant strains can evoke as a result of R-plasmid exchange within the hospital environment, providing an opportunity for control of this exchange can be interrupted.
Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences.
We have studied the transient expression of a cloned rabbit hemoglobin beta 1 gene after its introduction into HeLa cells. Two and one-half days after transfection using the calcium phosphate technique we extracted RNA from the entire cell population and analyzed it by the S1 nuclease hybridization assay. Transcripts were barely detectable when beta-globin gene-plasmid recombinants were used. However, 200 times more beta-globin gene transcripts were found when the beta-globin gene recombinants also contained SV40 DNA, and 90% of these transcripts (about 1000 per cell) had the same 5' end as authentic rabbit globin mRNA. In the latter case, abundant production of beta-globin protein was readily detected in a fraction of transfected cells by immunofluorescent staining. Enhancement of globin gene expression was dependent on SV40 sequences acting in cis, but independent of the viral origin of DNA replication. The enhancing activity was associated with the 72 bp repeated sequence element located at the beginning of the viral late gene region. Viral DNA fragments containing the transcriptional enhancer element could act in either orientation at many positions, including 1400 bp upstream or 3300 bp downstream from the transcription initiation site of the rabbit beta-globin gene. These studies define a class of DNA elements with a mode of action that has not been heretofore described. The activation of genes by specific enhancer elements seems to be a widespread mechanism that may be used for the regulation of gene expression.
Transformation of frog embryos with a rabbit beta-globin gene.
In order to study the fate and possible expression of foreign DNA during embryogenesis of the frog Xenopus laevis, we have injected a rabbit beta-globin gene into fertilized Xenopus eggs. Frog embryo DNA was extracted at various stages of development, fractionated by agarose gel electrophoresis, transferred to nitrocellulose filters, and hybridized to labeled beta-globin recombinant plasmid DNA. It was found that the injected DNA replicated extrachromosomally, reaching, at gastrula stage, a level equivalent to a 10- to 200-fold amplification of input DNA. At later stages, a majority of the foreign DNA was degraded, but a small fraction was maintained. Six-week-old tadpoles as well as six-month-old frogs contained an average of 3-10 copies of the rabbit globin gene per cell. Most of these persisting globin genes were present as long tandem repeats and comigrated in agarose gel electrophoresis with high molecular weight Xenopus DNA. Analysis of globin gene expression by S1 nuclease mapping showed that the rabbit beta-globin promoter was recognized in the frog embryo and that the transcripts were correctly spliced.
Evolution of a plasmid mediating resistance to multiple antimicrobial agents during a prolonged epidemic of nosocomial infections.
At the Vanderbilt University Medical Center, Nashville, Tennessee, resistance to gentamicin was encountered with increasing frequency among several species of gram-negative bacilli between 1973 and 1977. Representative strains were screened for plasmid DNA content using agarose gel electrophoresis. In strains of Pseudomonas aeruginosa and Serrati marcescens isolated early in the outbreak, gentamicin resistance was mediated by a common 9.8-megadalton nonconjugative plasmid. Either an 80- or a 100-megadalton transferable plasmid coexisted with the nonconjugative plasmid in the isolates of Serratia. Transposition between the 100- and 9.8-megadalton plasmids in this species resulted in the formation of a 105-megadalton conjugative plasmid that mediated gentamicin resistance; this was observed in strains of Serratia and Klebsiella isolated in 1976-1977. Thus, during this five-year investigation separate outbreaks of nosocomial infections that were caused by different bacterial species were shown to be related by the presence of plasmids that contained a common transposable DNA sequence.
Pseudodiphtheria: prominent pharyngeal membrane associated with fatal paraquat ingestion.
Three patients presented with prominent pharyngeal membranes suggestive of tonsillar-pharyngeal diphtheria, but later found to be caused by oral ingestion of the herbicide paraquat. In all cases appropriate therapy was delayed because of failure to include paraquat in the differential diagnosis: Paraquat ingestion should be considered in all patients with prominent tongue and pharyngeal membranes.
An outbreak of Legionnaires' disease associated with a contaminated air-conditioning cooling tower.
In August and September 1978, an outbreak of Legionnaires' disease occurred in Memphis, Tennessee. Of the 44 ill, 39 had been either patients, employees, visitors, or passers-by at one Memphis hospital (Hospital A) during the 10 days before. Assuming an incubation period of between two and 10 days, the onset of cases correlated precisely with the use of Hospital A's auxiliary air-conditioning cooling tower. L. pneumophila was recovered from two samples of water from the tower. Infection appeared to have occurred both outside and within the hospital. A significant association was demonstrated between acquisition of Legionnaires' disease and prior hospitalization in those areas of Hospital A that received ventilating air from air intakes near the auxiliary cooling tower. Tracer-smoke studies indicated that contaminated aerosols from the tower could easily reach these air intakes, as well as the street below, where four passers-by had been before they contracted Legionnaires' disease. This represents a common-source outbreak in which the source of L. pneumophila infection and airborne transmission were identified.
Direct transfer of cloned genes from bacteria to mammalian cells.
Induction of a virus infection by cloned simian virus 40 DNA was chosen as a test system to detect transfer of genes from bacteria to cultured mammalian cells. Escherichia coli cells containing a recombinant plasmid with three tandem inserts of simian virus 40 DNA were able to infect CV-1 monkey cells under various conditions. The gene transfer was resistant to DNase I and therefore seems not to occur via free DNA but most likely via uptake of whole bacteria, followed by release of plasmid DNA and generation of infectious circular simian virus 40 DNA in a recombination-excision process. Spontaneous transfer was found to be infrequent, 4 x 10(9) bacteria yielding one infection per 10(7) monkey cells. The frequency was greatly increased by adding bacteria as a calcium phosphate coprecipitate or by fusion of lysozyme-treated bacteria (protoplasts) with monkey cells in the presence of polyethylene glycol. With the latter technique, 10(4) protoplasts gave rise to one infection per 15 monkey cells. Experiments with other cell lines of human, monkey, and mouse origin, and also with bacteria harboring another recombinant plasmid, indicate that DNA transfer from bacteria to mammalian cells is a general phenomenon.
A study of antipsychotic drug use in nursing homes: epidemiologic evidence suggesting misuse.
We reviewed 384,326 prescriptions for 5,902 Medicaid patients residing continuously for one year in 173 Tennessee nursing homes. Of these patients, 43 per cent received antipsychotic drugs; 9 per cent were chronic recipients (received at least 365 daily doses per year). Of the 1,580 physicians who cared for these patients, 42 per cent prescribed antipsychotic medication. Physicians with large nursing home practices (10 or more patients) prescribed 81 per cent of the total antipsychotic medication, and were usually family practitioners (78 per cent) and in rural practice (47 per cent). As nursing home practice size increased, doctors prescribed more drug per patient (p less than .001). Wide variation in antipsychotic drug use occurred among nursing homes; the chronic recipient rate ranged from 0 to 46 per cent. More drug was given per patient in larger homes (r = .18, p less than .05). Typically, one physician (the "dominant" physician) provided care for the majority of a nursing home's patients. The proportion of a home's patients seen by the dominant physician was correlated with the chronic recipient rate (r = .17, p less than .05). These findings provide epidemiologic evidence suggesting misuse of antipsychotic drugs in nursing homes. They illustrate the need for investigations of techniques for patient management in nursing homes which rely less upon psychtropic drugs.
Identifying and discarding the myths of infection control.
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Infection control: time to justify the costs.
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Gram-negative bacillary sepsis associated with use of lipid emulsion in parenteral nutrition.
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Cutaneous myiasis in visitors to Central America.
Six cases of cutaneous myiasis occurred in three groups of visitors to Guatemala between February and May 1978. Attack rates ranged from 12% to 50%. Furuncular lesions were generally multiple and involved both exposed and usually unexposed areas of the body. Parasitic fly larvae recovered from two patients were identified as the botfly, Dermatobia hominis. Botfly infestation is endemic in areas of Central and South America and is acquired indirectly through the bite of carrier arthropods, including mosquitoes. Although reports of cases in North Americans visting endemic areas are rare, the condition is probably much more common in such persons than it is currently believed to be. A history of travel to Central or South America should suggest the diagnosis.
Sporadic cases of Legionnaires' disease: the expanding clinical spectrum.
An analysis of seven sporadic cases of Legionnaires' disease confirmed clinical features recorded during epidemics and identified aspects of the illness either unreported or not emphasized. Four patients had central nervous system abnormalities. Mental status changes included somnolence, obtundation, delirium, disorientation, and confusion. Three patients experienced visual hallucinations, and one patient without pneumonia had a grand mal seizure with residual memory deficit. Two patients had disseminated intravascular coagulation with thrombocytopenia, elevated split fibrin products, and prolonged partial thromboplastin and prothrombin times. Four patients had severe hypoxia; one patient had an exudative pleuritis. One patient whose treatment included erythromycin had radiologic improvement of his pneumonia despite deteriorating ventilatory function that led to death. The concept of Legionnaires' disease as a severe, diagnostically perplexing pneumonic illness is valid but too narrow. The emerging spectrum is that of a multisystem disease that, besides the lungs, often involves the central nervous system and can be accompanied by disseminated intravascular coagulation.
Legionnaires' disease in Kingport, Tennessee.
In August and September 1977 a discrete cluster of 27 serologically or pathologically confirmed cases of Legionnaires' disease, plus six highly presumptive cases were identified in the area of Kingsport, Tennessee. Three patients died. Most patients manifested severe pneumonia and fever; no mild or asymptomatic disease forms were recognized despite intensive case-finding efforts. Illness was epidemiologically associated with residing, visiting, or working in one geographic area of Kingsport, residence there being the factor most strongly associated. Although the attack rate for area residents was 0.64%, the randomly determined prevalence of serologic reactors was 5.2%, which is not significantly different from that in a nonimplicated control neighborhood. The epidemic did not correlate temporally with any identified environmental or demographic event. No source of the bacterium was found either by a detailed case-control study of area associations or by bacterial isolation from sentinel guinea pigs or environmental specimens. There was no evidence of person-to-person spread.
Chloramphenicol and tetracycline usage in outpatient practice.
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Drug prescribing during pregnancy. A controlled study of Tennessee Medicaid recipients.
The effect of pregnancy on prescribing was assessed in a population of pregnant Medicaid recipients and two matched groups of control women. Of the 2,528 gravidas, 62 per cent received systemic legend drugs (excluding dietary supplements) during their pregnancies. White women and women 30 years of age and older were most likely to receive these medications. Systemic anti-infectives were the most frequently prescribed category of drugs (excluding dietary supplements). One fourth of the women received a narcotic-containing drug and 13 percent of the women received psychotropic drugs, most frequently diazepam. Barbiturates and narcotic-containing drugs were often "hidden" a fixed combination medication. In general, prescribing did not decrease as a result of pregnancy. This study and other studies reviewed here emphasize the need for comprehensive drug-use guidelines for physicians who care for pregnant women.