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Biomedical subjects

W Schaffner

Publications and source records attributed to W Schaffner.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

Nursery epidemic due to multiply-resistant Klebsiella pneumoniae: epidemiologic setting and impact on perinatal health care delivery.

Gram-negative bacilli frequently cause epidemics in high-risk newborn intensive care units. Recently, an epidemic caused by a multiply-resistant K. pneumoniae, serotype 21, occurred in the Vanderbilt University intensive care nursery. The background of this outbreak included an increasing endemic nosocomial sepsis rate, operation of the facility in excess of rated capacity, and increasingly inadequate nurse-to-patient staffing ratios. The epidemic lasted 11 weeks; 26 (12%) of the 232 infants at risk in the unit became colonized. Five infants developed systemic illness and one died. Cohorting, reinforcement of strict handwashing and isolation procedures, and closure of the unit to outborn admissions resulted in rapid termination of the outbreak. Followup studies performed on infants colonized with the epidemic bacterium demonstrated persistent fecal shedding up to 13 months following discharge from the hospital. This epidemic had a detrimental influence on high-risk newborn and obstetric health care delivery in an area encompassing portions of three states. Under a system of progressively more sophisticated referral units, nosocomial infections occurring at a tertiary center can have an impact on other hospitals within the network.

Carrier State↗
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A lymphocyte-specific enhancer in the mouse immunoglobulin kappa gene.

During differentiation of lymphocytes into antibody-producing cells, an immunoglobulin kappa variable-region gene is transcriptionally activated by rearrangement linking it to a kappa constant (C kappa) region gene which is already transcribed prior to somatic rearrangement. The presence of a transcriptional enhancer element within the large intron of the kappa light-chain gene has been postulated to explain this mode of activation, supported by evidence of a chromatin region which is preferentially accessible to DNase I and restriction enzymes. This DNA region contains a segment of about 130 base pairs (bp) which is strongly conserved between mouse, rabbit and man. Moreover, no transcripts are detectable from a kappa gene, which is truncated within the large intron. Recently, a lymphocyte-specific enhancer has been identified downstream of the joining region in immunoglobulin heavy-chain genes. We now show direct evidence for a functionally similar enhancer within the large kappa gene intron of the mouse. It is, however, less active than the heavy-chain gene enhancer. In contrast, no enhancer was found to be associated with a cloned lambda I light-chain gene.

Animals↗
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Polyoma virus DNA replication requires an enhancer.

Sequences which activate polyoma virus DNA replication are located within a region that also includes the transcriptional enhancer. We demonstrate a cis involvement of enhancers in DNA replication by showing that this region can be replaced by other enhancers, in a position- and orientation-independent manner, and that an immunoglobulin gene enhancer confers tissue-specific replicatory ability.

DNA Replication↗
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Simian virus 40 enhancer increases RNA polymerase density within the linked gene.

Enhancers are regulatory DNA elements, usually about 200 base pairs (bp) long, which are able to stimulate transcription of linked genes in eukaryotic cells. This activation can be exerted over large distances, and from a position 5' or 3' to the gene. Enhancers have been identified in viral genomes and cellular genes. Using a transient expression assay, we have analysed transcription of the rabbit beta-globin gene and the thymidine kinase gene from herpes simplex virus with and without a simian virus 40 (SV40) enhancer. S1 nuclease mapping shows a high level of specific transcripts when the genes are linked to the enhancer. To determine whether this increased number of transcripts is due to a higher transcription rate, or perhaps to a shift from nonspecific to specific initiation, we have performed run-on transcription assays with isolated nuclei. Our results, presented here, demonstrate that the SV40 enhancer increases the RNA polymerase density within the linked gene. Therefore, enhancers apparently increase the rate of transcription initiation without influencing the specificity of initiation.

Cell Nucleus↗
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Pseudomonas folliculitis: an outbreak and review.

In November 1980, an outbreak of folliculitis due to Pseudomonas aeruginosa occurred in members of a health spa in Tennessee. The source of infection was traced to the health spa swimming pool, which had not been chlorinated for two days due to equipment malfunction. Thirty-seven (62%) of 60 members who used the swimming pool on these two days developed a papulopustular rash within eight hours to five days after swimming in the pool. The rash had a characteristic distribution, predominantly involving the buttocks, hips, and axillae. Other manifestations of infection included otitis externa (49%) and mastitis (11%). P. aeruginosa serogroup 0-11 was isolated from pustules of six people. A swab from the edge of the swimming pool also grew P. aeruginosa serogroup 0-11. With the rising popularity of home whirlpools and hot tubs, physicians may expect to encounter this disease with increasing frequency.

Disease Outbreaks↗
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Primary renal candidiasis with renal granulomata and salt-losing nephropathy.

A patient is reported whose illness was characterized by chronic renal failure associated with persistent salt-wasting, chronic nephrolithiasis, and candiduria which was documented to be arising from the upper urinary tract. Intravenous amphotericin B was effective in eradicating candiduria. However, bilateral nephrectomy was ultimately performed which revealed extensive involvement of the renal parenchyma with classic caseating granulomas apparently related to renal candidiasis. Severe medullary erosion and tissue loss existed which appeared to result in disproportionate medullary destruction which was probably the most significant factor in explaining the patient's salt-losing state. The patient has since been satisfactorily managed with maintenance hemodialysis.

Body Weight↗
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Statewide survey of the antimicrobial susceptibilities of Haemophilus influenzae producing invasive disease in Tennessee.

Between October 1, 1980, and September 30, 1981, a prospective statewide study of Haemophilus influenzae infections identified 220 culture-proved systemic infections. Of these, 92% were caused by H. influenzae type b. Antimicrobial susceptibility testing of the type b isolates showed that 17% were resistant to ampicillin, but virtually all were susceptible to chloramphenicol, trimethoprim-sulfamethoxazole, cefaclor and rifampin. Ampicillin resistance is common in all parts of Tennessee and chloramphenicol remains the drug of choice for initial therapy of systemic H. influenzae infections.

Ampicillin↗
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Extracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki Forest virus system.

Extracts, fractions and constituents of Hypericum perforatum were studied for in vitro receptor binding with various ligands to recombinant CNS receptors expressed with the Semliki Forest virus expression system. For this purpose we have prepared membranes of CHO cells with high density of several opioid, serotonin, estrogen, histamine, GABAA, neurokinin and metabotropic glutamate receptors, respectively. A lipophilic Hypericum fraction revealed relatively potent inhibition to the binding of the mu-, delta- and kappa-opioid and the 5-HT6 and 5-HT7 receptors. Moreover, Hypericum constituents such as the naphthodianthrones, hypericin and pseudohypericin, and the phloroglucinole hyperforin inhibited both binding to the opioid and serotonin receptors in the lower micromolar range. Estrogen binding was 50% inhibited by the biflavonoid I3,II8-biapigenin at micromolar concentration. The lipophilic Hypericum fraction provided a less potent inhibition of the neurokinin-1 receptor binding compared to the opioid and serotonin receptors. A total ethanolic Hypericum extract potently inhibited GABAA binding at approximately 3 micrograms/ml. This inhibition is however not specific to Hypericum, since extracts of plants like Valeriana officinalis and Passiflora incarnata showed similar inhibitions. Binding to neither histamine nor metabotropic glutamate receptors was affected by Hypericum extracts. These results support the hypothesis that several active constituents of Hypericum might in a synergistic way contribute to its antidepressant effect in the central nervous system.

Animals↗
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Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine.

We evaluated the risks of seizures and other neurological events following diphtheria-tetanus-pertussis (DTP) immunization for 38,171 Tennessee Medicaid children who received 107,154 DTP immunizations in their first 3 years of life. There were 2 children with encephalitis; both had disease onset more than 2 weeks following DTP immunization. There were 277 children who had febrile seizures, 42 with afebrile seizures, and 37 with seizures associated with other acute neurological illness (acute symptomatic). The risk of febrile seizures in the 0 to 3 days following DTP immunization (n = 6) was 1.5 (95% confidence interval, 0.6 to 3.3) times that of the control period 30 or more days following DTP immunization. There was no evidence that in the 0 to 3 days following DTP immunization the risk of afebrile seizures (n = 1) or acute symptomatic seizures (n = 0) was increased. No child who was previously normal without a prior history of seizures had a seizure in the 0 to 3 days following immunization that marked the onset of either epilepsy or other neurological or developmental abnormality.

Brain Diseases↗
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Reduction in motor vehicle fatalities associated with an increase in the minimum drinking age.

Motor vehicle injuries are responsible for nearly 40% of the deaths that occur among persons aged 15 through 24 years. Approximately half of these deaths involve drunk drivers. In response to the problem of driving under the influence of alcohol (DUI), some states raised their minimum drinking age, increased penalties for DUI, or both. Other states vigorously resisted federal pressure to increase their drinking age, and some researchers have questioned the utility of this approach. Tennessee increased penalties for DUI in 1982 and raised the drinking age to 21 years in 1984. Alcohol-related motor vehicle deaths declined by 33% among persons aged 15 through 18 years, probably because of publicity. Our results suggest that it may be particularly important to maintain continuous, high-profile anti-DUI programs within high schools. Alcohol-related motor vehicle deaths declined 38% among persons aged 19 through 20 years; this effect appears to be attributable to the increase in drinking age and to be durable despite decreased publicity.

Accidents, Traffic↗
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Persistence of improvement in antibiotic prescribing in office practice.

We evaluated persistence of the prescribing improvement seen in a previous statewide controlled trial, which measured improvement in the prescribing of contraindicated antibiotics and oral cephalosporins in the year after an educational intervention. Doctors visited by physician-counselors substantially improved their prescribing of both classes of drugs. The beneficial effect of the physician-counselors persisted throughout year 2, with attributable reductions in prescribing of 30% and savings of $950 for each doctor visited. The marked and lasting improvement in prescribing produced by the physician-counselors suggests using this model to develop ongoing programs to improve prescribing.

Anti-Bacterial Agents↗
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Pre-exposure immunization against rabies: a re-emphasis for veterinarians.

A serologic service for determining antibody levels due to prior rabies immunization was provided at an annual convention of the Tennessee Veterinary Medical Association in January 1977. A total of 26 veterinarians volunteered to participate, and only 2 had adequate serum levels of antibody related solely to a pre-exposure immunization. An additional six veterinarians had high titers of antibody-probably the result of post-exposure immunization after rabies-proved incidents. The level of protection for veterinarians appears to be low, which suggests a need for a re-emphasis on immunizations and for increased availability of the relatively new human diploid cell vaccine.

Humans↗