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Biomedical subjects

R S Baltimore

Publications and source records attributed to R S Baltimore.

At least 37 records · Page 2Linked to original sources
PubMed1990

A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience.

Records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates. Using a modification of objective Centers for Disease Control criteria to define sepsis, we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis. The sepsis rate for infants less than or equal to 30 days of age was 2.7 cases/1000 live births, with a mortality rate from sepsis of 15.9%. There was an increase in sepsis due to commensal species (CS) over the period (P less than 0.007). The number of infants in the nursery who developed sepsis when more than 30 days of age also increased (P less than 0.002), as did the rate of sepsis from CS in this group (P less than 0.001). Isolation of CS from the blood with fulfillment of the modified Centers for Disease Control criteria was associated with a 13.7% mortality rate, whereas isolation of CS without fulfillment was associated with a 4% rate (P less than 0.01).

Birth Weight↗
PubMed1989

Pertussis in neonates.

Despite the increasing prevalence of pertussis in young adults and infants, reports of maternal-neonatal pertussis are rare. Our study involves three neonates who apparently acquired pertussis from their adolescent mothers. The diagnosis of pertussis was initially missed in all of the patients. The mothers had mild respiratory disease. All three newborns presented with life-threatening coughing and choking spells without a characteristic inspiratory whoop. Two neonates had apnea, bradycardia, cyanosis, and unresponsiveness, but were without the initial lymphocytosis that is distinctive of pertussis. These two neonates had a clinical course that was consistent with the historic "100-day-cough." They required prolonged ventilatory support and hospitalization at a high cost. The other neonate had a terminal pulmonary hemorrhage. Strategies for the early diagnosis, treatment, and prevention of this potentially lethal disease in neonates are discussed.

Adolescent↗
PubMed1989

Epidemiology of pharyngeal colonization of infants with aerobic gram-negative rod bacteria.

By using a selective medium, pharyngeal colonization with gram-negative rod (GNR) bacteria was determined in a cohort of 49 normal infants monitored from birth to 6 months of age. Culture swabs were diluted in 1 ml of saline for quantitation. The prevalence of GNR in the first 72 h of life was 8% and rose to 29% during the first month, 52% at 2.5 months, 67% at 4.5 months, and 62% at 6 to 7 months. Colonization was with substantial numbers of organisms, generally greater than 100 colonies per ml and frequently greater than 1,000 colonies per ml. The most common species were Klebsiella species, Escherichia coli, Enterobacter species, and Acinetobacter anitratus. Fewer infants who were breast fed rather than formula fed at the time of culture harbored GNR (26 versus 45%, P less than 0.05). The point prevalence of pharyngeal GNR colonization in our special care nursery was 12 of 47 (26%), which was found to be similar to that of age-matched normal infants. GNR carriage in normal infants does not appear to be a residual of organisms acquired at birth, and interpretations of GNR carriage in ill or hospitalized infants should be evaluated by comparison with these data in healthy infants.

Age Factors↗
PubMed1989

Immunohistopathologic localization of Pseudomonas aeruginosa in lungs from patients with cystic fibrosis. Implications for the pathogenesis of progressive lung deterioration.

Despite studies of the pathologic and microbiologic aspects of the lung in cystic fibrosis (CF), there is a lack of information on the lung localization of bacterial pathogens. Bacteriologic data come from cultures of sputum or accessible lung effluent from bronchoscopy. Our objective was to localize Pseudomonas aeruginosa (PA) in situ in order to provide descriptive data on the relationship between the presence of PA and disease of the surrounding tissue. Using stored, uncut blocks of preserved lung, we deparaffinized, cut, mounted, and reacted them with high-titer rabbit sera made to a mucoid strain of PA. The tissues were then reacted with a second antibody, biotinylated goat antirabbit immunoglobulin, developed using a peroxidase technique and counterstained with hematoxylin. PA organisms stained with heavy brown deposits and this was species-specific. In five patients with CF chronically colonized with PA, the organisms could easily be localized in multiple sections. Microscopic study demonstrated that location was generally endobronchiolar and associated with bronchiolar obliterative changes, mainly in small (less than 1 mm) airways. Extraluminal PA organisms were rare even when there was chronic interstitial inflammation. This study demonstrated the presence of PA at the location where physiologic damage in CF is most severe--the small bronchioles--strengthening the association between PA and pulmonary deterioration in CF.

Adolescent↗
PubMed1987

The inhibitory effect of sodium alginate on antibiotic activity against mucoid and non-mucoid strains of Pseudomonas aeruginosa.

The exopolysaccharide of mucoid strains of Pseudomonas aeruginosa (MPA) is chemically similar to alginate, a common polysaccharide of seaweeds. Both polymers have been reported to decrease the diameter of the inhibition zones produced in antibiotic disc diffusion assays. In order to determine whether this phenomenon was due to reduced diffusion of the antibiotic in an agar matrix, or to inhibition of antibiotic activity by sodium alginate, we studied the effect of sodium alginate on the susceptibility of P. aeruginosa strains to antibiotics in disc diffusion assays, as well as in broth and agar dilution assays. Sodium alginate decreased the activity of the aminoglycoside antibiotics, amikacin and gentamicin, against two MPA strains and their non-mucoid derivatives in each of the assays. In broth dilution assays, increase of the calcium ion concentration likewise reduced aminoglycoside activity against P. aeruginosa, but not against Escherichia coli and Staphylococcus aureus. Sodium alginate caused no inhibition of the activity of piperacillin and carbenicillin. The reduction of aminoglycoside activity may have implications for the common failure of these antibiotics in the treatment of pulmonary infections caused by MPA in cystic fibrosis patients, but must be considered only an in-vitro phenomenon at present.

Alginates↗
PubMed1986

Antibody to multiple mucoid strains of Pseudomonas aeruginosa in patients with cystic fibrosis, measured by an enzyme-linked immunosorbent assay.

The sera from 32 patients with cystic fibrosis who were chronically colonized with mucoid strains of Pseudomonas aeruginosa (MPA) were tested for anti-MPA antibodies. Using an enzyme-linked immunosorbent assay we measured IgA, IgG, and IgM antibody titers to three MPA strains, extracts of those strains, and seaweed-derived sodium alginate, which is similar chemically to the exopolysaccharide of MPA. These titers were compared with identical tests performed on the sera of eight cystic fibrosis patients who never were colonized with MPA and 10 normal adults. The IgG titers were significantly higher in tests of sera from the colonized patients compared with the other two groups but the IgA and IgM titers were not significantly higher. In colonized patients antibody titers to the different antigens correlated with each other suggesting that the major antibody response was to common antigenic determinants. Using these titers as a data base, eight patients whose clinical status was unknown to the testers, had IgG-enzyme-linked immunosorbent assay tests of their sera and the four colonized patients with cystic fibrosis were correctly identified. Three of them had substantial titers of antibody in the bronchoalveolar lavage fluid.

Adult↗
PubMed1985

IgG proteolytic activity of Pseudomonas aeruginosa in cystic fibrosis.

To study how fragmented IgG antibodies might arise within the respiratory secretions of individuals with cystic fibrosis (CF), we screened protease extracts from CF polymorphonuclear leukocytes and mucoid and nonmucoid transformants of Pseudomonas aeruginosa from patients with CF for IgG proteolytic activity. All strains of P. aeruginosa tested exhibited IgG proteolytic activity. Incubation for 7 hr at 37 C was required to demonstrate generation of free Fc gamma immunoreactivity. Further analysis of these cleavage products of CF IgG demonstrated generation of Fc gamma polypeptides with 4S sedimentation coefficients and F(ab')2 fragments with 5S coefficients. Bacterial IgG proteolytic activity was inhibited by EDTA and was associated with levels of bacterial elastase exceeding 5 micrograms/mg of total protein. Pseudomonas elastase was significantly more active on IgG1 and IgG3; IgG2 and IgG4 were more resistant. This bacterial exoproduct appears to digest IgG molecules into Fab gamma, F(ab')2 fragments, and a free Fc gamma piece with a molecular weight of 40,000.

Cystic Fibrosis↗
PubMed1985

Prospects for a mucoid exopolysaccharide vaccine for the prevention of infection due to mucoid strains of Pseudomonas aeruginosa.

The problem of infection with MPA is virtually limited to pulmonary infection in patients with CF. Conventional vaccine strategies may not be appropriate because the pathogenesis and epidemiology of the infection is so different from the usual acute bacterial infections. MPA strains appear to be suited to long-term parasitism of immune hosts so initial prevention of colonization may be a necessary function of a vaccine. Since infected hosts have antibody to many antigenic components of PA, vaccines which have been used for PA up until now may not have any protective effect for patients with CF. If the switch from NMPA to MPA colonization in vivo is due to the development of host immunity, some vaccines could conceivably promote infection with MPA. A vaccine which produces antibody to the alginate-like mucoid exopolysaccharide might, however, discourage colonization with MPA and studies of this strategy should be promoted.

Animals↗
PubMed1984

Changing spectrum of infective endocarditis in children. Analysis of 26 cases, 1970-1979.

The decade of the 1970s was marked by an increased survival of children with complex heart lesions, use of prosthetic material in open heart surgery, and placement of indwelling central catheters in critically ill patients. We analyzed all 26 cases of children with infective endocarditis (IE) seen at Yale University, New Haven, Conn, from 1970 through 1979 to determine whether these and other factors resulted in a change in pediatric IE. A larger proportion of cases arose postoperatively as compared with previous series. Among the postsurgical and catheterization-related cases, the most common infecting agents were streptococci, not the expected staphylococci. Although the number of cases was small, IE associated with prosthetic material had a favorable prognosis; all survivors of IE with prosthetic material were cured by medical regimens alone. The IE cases in children with previously normal hearts were associated with indwelling central catheters.

Anti-Bacterial Agents↗
PubMed1983

The role of complement in the opsonization of mucoid and non-mucoid strains of Pseudomonas aeruginosa.

Requirements for complement and/or antibody for opsonization were assessed for 34 strains of Pseudomonas aeruginosa. Included were mucoid strains from patients with cystic fibrosis (CF), non-mucoid derivatives of these strains, and non-CF strains with classical morphology. Non-CF strains are known to vary as to opsonic requirements, but this study shows that mucoid strains are also diverse. Among the 14 mucoid strains, five could not be opsonized and completely resisted phagocytosis. All non-mucoid strains can be opsonized. When the bacteria were incubated in fresh human serum and stained with fluorescein, conjugated anti-C3 non-opsonizable strains did not bind C3 on the surface whereas five of six mucoid strains, which could be opsonized by complement alone, stained with anti-C3. In mucoid strains, surface characteristics correlate with differences in functional requirements for opsonization. In non-CF strains this specificity was not seen. Most mucoid strains required an intact classical complement pathway for opsonization. A number of mucoid strains could not be opsonized in the absence of a functional alternative complement pathway whereas in contrast, non-CF strains were not greatly affected by inactivation of the alternative pathway.

Antibodies, Bacterial↗
PubMed1982

Effect of iron saturation on the bacteriostasis of human serum: in vivo does not correlate with in vitro saturation.

Human serum inhibits the growth of a variety of human pathogens. One of the serum bacteriostatic components is transferrin, the major iron-binding protein. In the presence of transferrin, free iron, which is required for bacterial nucleoprotein synthesis, is unavailable and bacterial growth is inhibited. In an in vitro system, we tested the hypothesis that serum with highly saturated transferrin allows free iron to be available for rapid bacterial growth. We first confirmed the finding that addition of ionic iron sufficient to saturate transferrin in normal sera inhibits the bacteriostatic activity for Escherichia coli. In contrast, no differences were found in the growth rate of E. coli in sera from individuals representing the entire range of transferrin saturation found in humans (iron-deficient, normal, and thalassemic). This finding supports the thesis that iron added in vitro is more easily extracted than in vivo, where it is tightly bound to transferrin, and does not support the contention that ordinary iron treatment predisposes infants to infection.

Adolescent↗
PubMed1982

Occurrence of nonfermentative gram-negative rods other than Pseudomonas aeruginosa in the respiratory tract of children with cystic fibrosis.

There have been no comprehensive microbiologic studies of the frequency of respiratory colonization with nonfermentative gram-negative rods (NFGNR) other than Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Records of bacteria isolated from throats and sputa of CF patients of the Yale-New Haven Hospital CF Clinic from 1975-1979 were reviewed in order to determine the incidence of these species. Thirty-one strains were recovered. Twenty patients from the CF Clinic (with an average census of 170 patients) yielded at least one isolate of non-P. aeruginosa NFGNR, and eight of them showed more than one species on at least one occasion. Two patients also carried P. aeruginosa and ten carried Staphylococcus aureus on at least one occasion. Using a standardized method of clinical scoring, our patients had a course not unlike our general CF population.

Acinetobacter↗
PubMed1981

Pasteurella multocida. Osteomyelitis following dog bites.

Two cases of Pasteurella multocida osteomyelitis occurred following dog bit injuries. Difficulties exist in diagnosis and treatment. The role of P Multocida and other dog mouth flora in the pathogenesis of infectious complications following dog bites is discussed. we urge a flexible antimicrobial approach based on culture results.

Adolescent↗
PubMed1981

Effects of route and time of administration of antiserum on protection of mice from lethal infection due to group B Streptococcus type III.

The present study examines a mouse model of infection due to group B Streptococcus serotype III (GBS-III) as to the route and timing of antiserum administration for protection and quantitation of bacteremia with and without antiserum. Data for these parameters are contrasted with those after challenge with serotype Ia of group B Streptococcus (GBS-Ia). An intraperitoneal injection of GBS organisms and protective antiserum from a single syringe can be used to create an animal model of disease. Intraperitoneal injection of GBS-III resulted in bacteremia at 0.5 h both in animals who did not receive antiserum (17.4 X 10(2) +/- 7.6 X 10(2) colony-forming units per ml of blood samples) and in animals who received antiserum (19.3 X 10(1) +/- 6.8 X 10(1) colony-forming units per ml). Although intraperitoneal injection of GBS-Ia also resulted in bacteremia evident by 0.5 h in unprotected animals (30.1 X 10(2) +/- 3.8 X 10(2) colony-forming units per ml), no bacteremia occurred in protected recipients of this organism. Bacteremia due to GBS-Ia and GBS-III logarithmically increased until at least 7 h. Bacteremia due to GBS-III in protected animals was cleared by 24 h. Protection against GBS disease did not require simultaneous or proximate administration of the organism and the antiserum. Mice could be protected from death after intraperitoneal challenge with GBS-III or GBS-Ia by antiserum administered intravenously or intraperitoneally from 6 h before to 2.5 h after challenge.

Animals↗