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Biomedical subjects

R L Thompson

Publications and source records attributed to R L Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1985

Mycotic pseudoaneurysm of an aortic bypass graft and contiguous vertebral osteomyelitis due to Aspergillus fumigatus.

Fungal osteomyelitis is rare in patients who are not immunocompromised. This report documents that Aspergillus vertebral osteomyelitis may, however, be associated with infection of an adjacent prosthetic vascular graft in the absence of overt immunosuppression. A 73-year-old man is described with a mycotic pseudoaneurysm of a Dacron aortic bypass graft and contiguous vertebral osteomyelitis due to Aspergillus fumigatus. The patient was successfully treated with resection of the infected graft and administration of amphotericin B in a total dose of 2 g. Infection may have occurred intraoperatively as a result of inoculation with airborne fungal elements.

Aged↗
PubMed1985

A simulation of T4 bacteriophage assembly and operation.

A model is presented for the self-assembly and operation of a bacteriophage comparable with the T4 bacteriophage that infects Escherichia coli. The model treats protein molecules as simple units obeying the principle free energy minimization, and exhibiting the properties of quasi-equivalence and conformational switching. A computer program incorporating the model has been developed. The results of simulation using this program are presented.

Adsorption↗
PubMed1985

Rescue of a herpes simplex virus type 1 neurovirulence function with a cloned DNA fragment.

A herpes simplex virus type 1 (HSV-1) genetic function that is required for viral replication in the murine central nervous system was unambiguously localized. Thus, cosmid clones of either HSV-1 HindIII fragment C (0.64 to 0.87 map units) or fragment B (0.64 to 0.83 plus 0.91 to 1.0 map units) were employed to restore neurovirulence to an intertypic recombinant (RE6) that is specifically deficient in this property. The neurovirulent recombinants were generated in cell culture by cotransfecting the clone fragments and unit-length RE6 DNA and then selected in mouse brains. Either fragment efficiently conferred neurovirulence to RE6, demonstrating that no short region unique sequences are required. Analyses of the genomic structures of the neurovirulent recombinants showed that, in every case, HSV-1 information from 0.71 to 0.83 map units was incorporated into the RE6 genome. Cleavage of HindIII fragment C with EcoRI eliminated its capacity to rescue RE6. Virulence could be restored by the addition of HSV-1 BamHI fragment L (0.71 to 0.74 map units) that spans an EcoRI site at 0.72 map units. The precise location of this HSV-1 neurovirulence function is discussed.

Animals↗
PubMed1985

Virus-induced modification of the host cell is required for expression of the bacterial chloramphenicol acetyltransferase gene controlled by a late herpes simplex virus promoter (VP5).

The requirements for expression of genes under the control of early (alkaline exonuclease) and late (VP5) herpes simplex virus type 1 (HSV-1) gene promoters were examined in a transient expression assay, using the bacterial chloramphenicol acetyltransferase gene as an expression marker. Both promoters were induced, resulting in the production of high levels of the enzyme upon low-multiplicity infection by HSV-1. S1 nuclease analysis of hybrids between RNA isolated from infected cells containing HSV-1 promoter constructs and marker gene DNA demonstrated normal transcriptional initiation of the marker gene directed by the viral promoters. Viral DNA sequences no more than 125 bases 5' of the putative transcriptional cap site were sufficient for maximum activity of the late promoter. In contrast to expression controlled by the early gene, the late promoter was not active at a measurable level in uninfected cells until DNA sequences between 75 and 125 bases 5' of the transcriptional cap site were deleted. Cotransfection of cells with the expression marker controlled by HSV promoters and a cosmid containing HSV alpha (immediate-early) genes indicated that full expression of both early and late promoters requires the same virus-induced host cell modifications. Inhibition of viral DNA synthesis results in an increased rate of transient expression of marker genes under control of either early or late promoters in contrast to the situation in normal virus infection. These data provide evidence that the normal course of expression of late HSV genes involves negative modulation of potentially active promoters in the infected cell.

Acetyltransferases↗
PubMed1984

Catheter-associated bacteriuria. Failure to reduce attack rates using periodic instillations of a disinfectant into urinary drainage systems.

We assessed the efficacy of periodic instillations of hydrogen peroxide into urinary drainage systems in the prevention of catheter-associated bacteriuria in a prospective and randomized clinical study of 668 patients with indwelling urethral catheters. Bacteriuria was documented in 68 (10%) of the 668 patients after a mean duration of four days of catheterization. There was no difference between the hydrogen peroxide group and the control group in the mean duration of catheterization before the onset of bacteriuria, in the attack rate for bacteriuria, or in the spectrum of etiologic agents recovered. Bag contamination with the same organism responsible for bacteriuria preceded infection in only five (7%) of the 68 patients, three patients using hydrogen peroxide and two in the control group. We conclude that infections arising intraluminally from contamination of the drainage bag are uncommon among catheterized patients and that the periodic instillation of disinfectants into closed sterile drainage systems is not effective in reducing the incidence of catheter-associated bacteriuria.

Bacteria↗
PubMed1984

Cefsulodin sodium therapy in cystic fibrosis patients.

Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa. We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa. The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days. Mean peak drug levels in plasma after 500, 1,000, and 1,500 mg were 46, 71, and 90 micrograms/ml, respectively, and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml. Detectable levels of cefsulodin in sputa were found in approximately half of the random samples and ranged from 2 to 5 micrograms/ml. The clinical response was satisfactory in nine (90%) of the patients. One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values. In pulmonary function tests, four of five patients tested showed an average 43% increase in forced vital capacity after initiation of therapy and five of five had an average 51% increase in forced expired volume in 1 s. No adverse effects were observed.

Adolescent↗
PubMed1984

Antimicrobial therapy in musculoskeletal surgery.

The treatment of musculoskeletal infections often involves a combined surgical and antibiotic approach. The antimicrobial therapy of these infections does not differ in basic principles from that of other infections. Because many different microorganisms can cause musculoskeletal infection, appropriate antimicrobial therapy depends on proper culturing, isolation, identification, and antibiotic susceptibility testing of the etiologic infectious agent. The need for long-term treatment makes the proper selection of antibiotic and monitoring of therapy imperative. The least toxic, least expensive, and most effective antibiotic should be selected.

Aminoglycosides↗
PubMed1983

Biological characterization of a herpes simplex virus intertypic recombinant which is completely and specifically non-neurovirulent.

In this study, a pre-existing "library" of Herpes Simplex Virus (HSV) intertypic recombinants was found to be not useful for mapping HSV genes controlling viral neurovirulence in mice. Most of these agents were significantly less virulent than either parental type following intracranial inoculation, and in the general case this lessened virulence could be attributed to inefficient replication in any cell type at 38.5 degrees (the normal temperature of the mouse). One agent tested (recombinant RE6) was completely non-neurovirulent following intracranial inoculation of as much as 3.2 X 10(7) PFU. Since about 10 PFU of either 17 Syn+ or HG52 (the "parental" strains of this recombinant) were lethal for mice, RE6 is at least 10 million-fold less neurovirulent than the wild-type strains from which it was produced. The function of the defective gene(s) in RE6 is not yet known, but it is not required for the expression of viral thymidine kinase, efficient replication in cultured cells at 38.5 degrees, or replication in non-neural mouse tissue in vivo. Therefore, the defect in RE6 is in an HSV gene function(s) which is absolutely required for neurovirulence but not for general viral replication. Several possibilities for the molecular nature of the defect in RE6 are discussed.

Animals↗
PubMed1983

Physical location of a herpes simplex virus type-1 gene function(s) specifically associated with a 10 million-fold increase in HSV neurovirulence.

In this paper we present a technique developed to physically locate the HSV-1 gene(s) which restore neurovirulence to a non-neurovirulent HSV intertypic recombinant described in the preceding report. In brief, tissue culture cells are co-transfected with unit length RE6 DNA and restriction endonuclease fragmented HSV-1 (strain 17 Syn+) DNA. In this way, random recombinations between RE6 and 17 Syn+ are produced. An in vivo enrichment in mouse brains is then employed to select recombinants which have incorporated the HSV-1 gene(s) associated with neurovirulence. In each of five cases where neurovirulent recombinants were isolated by this procedure, restriction enzyme and Southern DNA transfer analysis revealed that HSV-1 information from 0.71 to 0.83 map units had been incorporated into the RE6 genome. Confirmation of the role of this portion of the genome for HSV neurovirulence was obtained by similar cotransfection and in vivo rescue experiments performed with an electrophoretically purified HSV-1 DNA fragment which encompasses this region. Subsequent genome structure analysis of neurovirulent recombinants generated by this procedure revealed that only type-1 information from 0.71 to 0.83 map units had been incorporated into RE6. Thus an HSV-1 gene function(s) which resides in this region of the viral DNA is associated with a 10 million-fold increase in the neurovirulence of the virus. Potential applications of this in vivo selection technique are discussed.

Animals↗
PubMed1983

Serology of Staphylococcus aureus infections using multiple antigens and serial serum samples.

The detection of antibody to S aureus in human serum can aid in the management of staphylococcal diseases [1]. RIAs and ELISAs can detect low levels of antibody and demonstrate increased antibody production during serious staphylococcal infections [2,3]. We compared four S aureus constituents--cell-wall peptidoglycan and teichoic acid, and extracellular alpha-toxin and nuclease--as antigens in a sensitive ELISA. The value of testing more than a single serum sample was also determined. Elevated IgG antibody to peptidoglycan, present in one or more serum samples of 13 (50%) of 26 patients with complicated bacteremia, was found to be the most sensitive test. All 26 patients had a significant IgG antibody response to peptidoglycan. Three (27%) of 11 patients with uncomplicated bacteremia had elevated levels of antibody to peptidoglycan in their serum, and seven (64%) showed a significant change in titer when serial serum samples were tested. Maximum detection rates for the other antigens in complicated and uncomplicated bacteremia were, respectively, 62% and 37% for teichoic acid, 38% and 37% for nuclease, and 54% and 13% for alpha-toxin. In single serum samples, the detection rate for all four antigens marginally improved the results, with detection rates of 62% and 36% for complicated and uncomplicated bacteremia, respectively. Cross-reactive antibody to peptidoglycan but not to the other three antigens was present in six (75%) of eight patients with long-standing subacute bacterial endocarditis due to either viridans streptococci or Staphylococcus epidermidis (data not shown).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1983

Replication at body temperature selects a neurovirulent herpes simplex virus type 2.

A prototype strain of herpes simplex virus type 2 (HG-52) replicated at 31 degrees C was avirulent when inoculated intracranially into mice. This property was not altered after serial passage of the agent at 31 degrees C, but the virus became virulent after passage at 37.5 degrees C. The selection was not merely for an agent which replicated more efficiently at the higher temperature, but for viruses with enhanced capacity to replicate in the brains of mice. Virulent descendants of plaque-purified avirulent stocks were obtained in each instance attempted.

Animals↗
PubMed1983

Microbiological and clinical evaluation of the isolator lysis-centrifugation blood culture tube.

In a controlled evaluation of 6,010 blood cultures, the yield of clinically significant microorganisms was greater from a lysis-centrifugation system (Isolator, Du Pont Co.) than from a nonvented vacuum bottle containing tryptic soy broth with sodium polyanetholesulfonate and CO2 and a vented bottle containing biphasic brain heart infusion medium with sodium polyanetholesulfonate. The Isolator significantly increased the frequency of isolation of Staphylococcus aureus and Candida spp. and significantly decreased the time required for the detection of S. aureus, Pseudomonas aeruginosa, and Candida spp.; however, anaerobic bacteria were recovered significantly more frequently from nonvented bottles with tryptic soy broth, and pneumococci were recovered significantly more frequently from both bottle systems. Contamination of cultures was significantly greater with the Isolator system than with either bottle system. Regardless of the number of blood cultures obtained per septic episode, the Isolator detected microbiologically proven bacteremia or fungemia in a significantly greater number of patients and significantly decreased the time required for detection.

Adult↗