Biomedical subjects
J R Johnson
Publications and source records attributed to J R Johnson.
Rapid classification of positive blood cultures.
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Immunologic purging of marrow assessed by polymerase chain reaction.
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Diagnosing Lyme disease.
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Success of DNA fingerprinting after failure of biotyping, antimicrobial susceptibility testing, and plasmid analysis to reveal clonality of multiple blood and urine isolates from a patient with Escherichia coli urosepsis.
Multiple isolates of Escherichia coli from the blood and urine of a 60-year-old woman with acute pyelonephritis exhibited different biotypes, antimicrobial susceptibility patterns, and plasmid profiles, suggesting the presence of polymicrobial bacteriuria and leaving in question the origin of the bacteremia. Only after bacterial restriction endonuclease analysis of total bacterial DNA was it discovered that all isolates represented the same strain, with plasmid instability possibly accounting for the varied antimicrobial susceptibility patterns observed. We conclude that the biotype, antimicrobial susceptibility profile, and plasmid profile are sometimes inadequate to clarify the relationships between different clinical isolates of E. coli from a single patient and can lead to erroneous epidemiologic conclusions. DNA fingerprinting can resolve dilemmas these less precise techniques leave unresolved.
Measurement of blood flow rates in the lower extremities with use of a nuclear magnetic resonance based instrument.
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Detailed histopathological examination contributes to the assessment of Escherichia coli urovirulence.
To determine the usefulness of detailed histopathological evaluation in the assessment of urovirulence of different Escherichia coli strains in a mouse model of ascending, unobstructed urinary tract infection, and to evaluate the relationship between susceptibility to urinary tract infection and renal levels of P fimbrial receptor glycolipids in different mouse strains, female Swiss Webster and Balb/c mice were inoculated transurethrally with one of four different well-characterized wild type E. coli strains or with an E. coli K-12 laboratory strain, and renal glycolipid levels were determined for both mouse strains. In Swiss Webster mice, each of the wild type E. coli strains was more virulent than the laboratory strain by both microbiological and histopathological criteria. Despite the common origin and identical virulence factor profiles of the three urosepsis isolates studied, one was significantly less urovirulent than the other two. Paradoxically, this strain stimulated a greater degree of leukocytosis than did the more urovirulent strains. Balb/c mice were significantly more susceptible to infection with this strain than were Swiss Webster mice, a difference possibly contributed to by the significantly higher renal levels of P fimbrial receptor glycolipids in Balb/c mice. Detailed histopathological analysis revealed significant differences in virulence between bacterial strains, and in susceptibility to infection between different mouse strains, that were inapparent from culture results alone.
Renal ultrasonographic correlates of acute pyelonephritis.
To determine the frequency and clinical significance of ultrasonographically detectable alterations in renal volume and anatomy that are associated with acute pyelonephritis, 25 women underwent renal ultrasonography during the acute phase of their illness, and 21 of these patients underwent the procedure after receiving antimicrobial therapy. One patient had a predisposing anatomic abnormality (4%; 95% confidence interval, 0-12%), and one patient each (8%; 95% confidence interval, 0-19%) experienced focal complications (an intrarenal mass and perinephric fluid collection). The kidneys of the 21 evaluable patients were acutely swollen (mean, 20%; P = .0001); one or both kidneys were enlarged by greater than or equal to 15% in 17 (81%). Acute renal enlargement was associated with protracted pretherapy symptoms (P less than .01), leukocytosis (P less than .01), focal infectious complications (P less than .01), and prolonged hospitalization (P less than .05). Thus, ultrasonographically demonstrable renal swelling characteristically occurs in women with acute pyelonephritis but is usually apparent only in retrospect. The degree of swelling correlates with selected clinical parameters, and the frequency of underlying anatomic abnormalities and focal infectious complications is low.
Hepatitis due to herpes simplex virus in marrow-transplant recipients.
Eight cases of hepatitis due to herpes simplex virus (HSV) (five "confirmed," three "possible") were identified among marrow-transplant recipients at the Fred Hutchinson Cancer Research Center between 1975 and 1988. The clinical and pathological characteristics of these patients are described and compared with published findings for non-marrow-transplant recipients with HSV hepatitis. Clinical syndromes in the marrow-transplant recipients ranged from fever associated with abdominal pain and elevations in serum aminotransferase levels to fulminant hepatitis. Evidence of hepatic infection appeared before day 20 following transplantation unless prophylaxis with acyclovir was given, in which case HSV hepatitis did not appear until after day 40. All patients died, although the one patient who was given early, empirical high-dose acyclovir therapy clearly improved with antiviral therapy and may have died of other causes. Involvement of multiple organs with HSV was found in three of four patients with confirmed HSV hepatitis who underwent autopsy. In all cases, reactivation of latent HSV was the presumed source of the HSV hepatitis. HSV hepatitis should be considered when HSV-seropositive recipients of marrow transplants develop abdominal pain, fever, and elevations in aminotransferase levels.
Histopathologic-microbiologic correlates of invasiveness in a mouse model of ascending unobstructed urinary tract infection.
To clarify the usefulness of histopathology in evaluating invasiveness during acute cystitis and pyelonephritis in a mouse model of urinary tract infection, findings from bladder and kidney sections of mice inoculated transurethrally with Escherichia coli were compared with results of bladder, kidney, spleen, and blood cultures and with changes in peripheral blood leukocyte counts. All of the 14 bladder histopathologic abnormalities evaluated were significantly associated with a positive bladder culture, and 7 were associated with splenic infection. Histopathologic features of cystitis were present in some culture-negative bladders. Eleven of 12 renal histopathologic abnormalities evaluated were significantly associated both with a positive kidney culture and with splenic infection, and two correlated with the development of peripheral leukocytosis. Histopathologic features of pyelitis and nephritis permitted culture-positive kidneys to be categorized as exhibiting colonization only, pyelitis only, or pyelitis plus frank nephritis and demonstrated that some culture-negative kidneys exhibit signs of pyelitis and nephritis. These findings suggest that detailed, semiquantitative histopathologic evaluation can add to quantitative cultures in the assessment of bacterial urovirulence in the mouse model of ascending urinary tract infection.
Enalapril and reversible acute renal failure.
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The use of antibiotic-impregnated polymethylmethacrylate beads to prevent the evolution of localized infection.
The effect of antibiotic bead chains on the evolution of infection cannot be studied entirely in man due to the ethical problems of obtaining valid controls. Therefore, a model of musculoskeletal injury was devised in rabbits by making a paraspinal wound, fracturing a spinous process, and contaminating the wound with 1 x 10(4) colony-forming units/ml of Staphylococcus aureus. These contaminated wounds were treated with tobramycin-containing polymethylmethacrylate (PMMA) beads. Control rabbits were either treated with PMMA beads that did not contain antibiotic, treated with IM tobramycin, or left untreated. At 5 days, six of eight animals treated with antibiotic-impregnated beads had no recoverable organisms. Six of eight rabbits receiving IM tobramycin had wound infections, and five of five in whom non-antibiotic-containing beads had been implanted had significant wound infections, with one of the five dying of sepsis on the 3rd day of the experiment. The clinical course of infected controls was the same as the course of those animals receiving IM antibiotics and the same as those in whom beads without antibiotics were implanted. That is, the rabbits had grossly infected wounds and the organisms recovered were of the same type as those implanted. This research shows a highly statistically significant effect of tobramycin-containing antibiotic beads in retarding the evolution of an experimental Staphylococcus infection in rabbits.
Seatbelt injuries in children.
Twelve cases of Chance-type flexion-distraction injuries in children less than 16 years old were reviewed. Patients were evaluated in terms of initial treatment regimen, subsequent modifications, and ultimate outcome. Follow-up ranged from 6 months to 9 years. Seven patients with a significant ligamentous component to their injury were initially treated, for various reasons, in a brace. All patients responding to brace treatment had an initial kyphotic deformity of less than 20 degrees and a maximum measured deformity of less than 25 degrees. In patients in whom brace treatment failed, initial deformity was greater than 20 degrees in all cases. Kyphotic deformity progressed to greater than 30 degrees before surgical intervention in these four cases. Improved adherence to lap seatbelt precautions, while of great benefit in reducing motor vehicle-related morbidity and mortality, has simultaneously increased the likelihood of flexion-distraction lumbar spine injuries. Our results suggest that an approach to treatment designed specifically for children is appropriate.
Cotrel-Dubousset instrumentation in idiopathic scoliosis.
Although well accepted in the patient undergoing Harrington instrumentation, the validity of King's criteria in patients undergoing correction of idiopathic scoliosis using the Cotrel-Dubousset system has been questioned. The cases of 64 patients with Type II (N = 40) and Type III (N = 24) idiopathic scoliosis treated with Cotrel-Dubousset instrumentation were reviewed. The average curve correction for Type II spinal curvature was 69.4% after surgery and 57.8% at follow-up examination. Decompensation was evident in 40% of the curves that were fused beyond the stable vertebra. However, the patients were only aware of their trunk decompensation if it was larger than 10 mm, and this was found in 35% of the patients. Decompensation occurred in 60% of those that were fused short of or to the stable vertebra. Only 42% of this group were aware of their decompensation. Decompensation was measured to the left of the spine in all patients. The difference between the subgroups based on the choice of distal fusion levels was not statistically significant (P greater than 0.05). The average curve correction for Type III scoliosis was 62.9% after surgery and 54.6% at the time of follow-up examination. There was no correlation between caudal fusion levels and the incidence of decompensation with Type III curves. It was concluded that there was no statistically significant relationship between choice of distal fusion level and the amount of decompensation, thereby indicating that the use of King's criteria for the selection of fusion levels in patients undergoing correction of idiopathic scoliosis using the Cotrel-Dubousset instrumentation may not be useful.
Avian P1 antigens inhibit agglutination mediated by P fimbriae of uropathogenic Escherichia coli.
Whole egg white from pigeon, dove, and cockatiel eggs, as well as the ovomucoid fraction of pigeon egg white, exhibited strong P1 antigenic activities and inhibited agglutination of human P1 erythrocytes and of digalactoside-coated latex beads by P-fimbriated Escherichia coli strains. In contrast, chicken egg white exhibited only weak P1 antigenic activity and had little impact on P-fimbrial agglutination. These preparations did not affect hemagglutination by E. coli strains expressing mannose-resistant adhesins other than P fimbriae, i.e., Dr, F1845, and S adhesins. Human anti-P1 serum diminished the P-fimbrial inhibitory activities of pigeon egg white and pigeon ovomucoid. Pigeon ovomucoid was equipotent on a molar basis with globoside, and the pigeon, dove, and cockatiel egg white preparations were equipotent with each other in P-fimbrial inhibition. Incubation of p erythrocytes in whole egg whites or in pigeon ovomucoid did not render them agglutinable by P-fimbriated bacteria, whereas incubation in globoside did. These data demonstrate that whole egg whites (and their ovomucoid fraction) from members of the families Columbidae (pigeons and doves) and Psittacidae (parrots) specifically and potently inhibit P-fimbrial agglutination, probably by providing P1 antigen as a receptor for the P-fimbrial adhesin. Avian egg white preparations may facilitate adhesin characterization of wild-type uropathogenic strains and may useful in preventing upper urinary tract infections due to P-fimbriated E. coli.
Pyogenic infections of the spine.
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Increased gut permeability following burn trauma.
Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full-thickness burn injury. Gastrointestinal permeability was assessed before burn and on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary excretion for the next 7 hours. In normal guinea pigs, lactulose (molecular weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose (molecular weight, 164 d) is mostly absorbed by the transcellular route. Gut permeability to L-rhamnose did not increase after burn injury (211 micrograms before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). By contrast, gut permeability to lactulose increased significantly and was greatest in the first 48 hours after burn injury (60 micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). Gut permeability to low-molecular-weight compounds increases immediately after burn trauma, and this may be by a paracellular rather than transcellular mechanism.
Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution.
The effect of tablet formulation solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants" (sodium starch glycolate, crospovidone, and croscarmellose sodium) in tablets prepared by wet granulation was investigated. Lactose, calcium phosphate dibasic, sorbitol, and naproxen sodium, alone or in combination, provided varying degrees of solubility and hygroscopicity in the formulations. To monitor in vitro dissolution, 1% p-aminobenzoic acid was added to the formulation as a tracer. The results indicate that highly soluble and/or hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity and solubility of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant.