Biliary atresia in two sets of twins.
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Biomedical subjects
Publications and source records attributed to K Shannon.
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The in-vitro activities of enoxacin and ofloxacin were compared with that of the other new 4-quinolone, ciprofloxacin. All three compounds were highly active against Enterobacteriaceae, Haemophilus influenzae and Neisseria gonorrhoeae (MICs mostly less than 1 mg/l). The other Gram-negative aerobes tested were in general less susceptible, though for Acinetobacter and Pseudomonas species (including aeruginosa) MICs seldom exceeded 8 mg/l. Ofloxacin and ciprofloxacin were more active against Gardnerella vaginalis (MICs 0.5-2 mg/l) than was enoxacin (MICs 8-32 mg/l). Staphylococci were susceptible to ofloxacin (MICs 0.12-1 mg/l) and enoxacin (MICs 0.5-2 mg/l) as well as to ciprofloxacin. Streptococci also were mostly sensitive to the compounds though the MICs of enoxacin (4-64 mg/l) were noticeably higher than those of ofloxacin (1-4 mg/l). Anaerobes were in general susceptible though, as with streptococci, ofloxacin, with activity similar to that of ciprofloxacin, was more active than enoxacin. Variants of Enterobacteriaceae with reduced susceptibility were readily selected in the laboratory with either enoxacin or ofloxacin as the selective agent. The MICs of all the 4-quinolones were usually increased four- to 16-fold for these strains; they could therefore be regarded as remaining susceptible to the newer compounds.
The in-vitro activity of the penem Sch 34343 was assessed in comparison with third-generation cephalosporins, aztreonam and imipenem. Sch 34343 was active, with MICs generally 2 mg/1 or less, against a broad spectrum of organisms amongst which were staphylococci (including methicillin-resistant strains), streptococci (though enterococci were less susceptible with Sch 34343 MICs mostly 4-8 mg/1), anaerobes (including the Bacteroides fragilis group), Haemophilus influenzae and Neisseria gonorrhoeae. It was also active against the Enterobacteriaceae though Enterobacter cloacae and Serratia spp. were somewhat less susceptible than other members of this group. Sch 34343 lacked useful activity against most species of Pseudomonas (including Ps. aeruginosa) but was active against Ps. acidovorans and some isolates of Ps. cepacia. Sch 34343 showed a high degree of resistance to plasmid-determined and most chromosomally-determined beta-lactamases; however, it was hydrolysed rapidly by enzymes from some isolates of Aeromonas hydrophila and more slowly by enzymes from Ps. maltophilia and Bact. melaninogenicus subspecies intermedius. We did not observe any reduction in sensitivity to Sch 34343 for most beta-lactamase-producing organisms, including strains of Enterobacter spp. and Citrobacter freundii that were resistant to most other beta-lactams.
There were 658 positive blood cultures in St. Thomas' Hospital during 1982-1984, from which 301 Enterobacteriaceae were isolated. Most were of species that do not usually produce inducible class I beta-lactamases but 39 of the isolates were of species that do. Many of these strains were resistant to the older cephalosporins but resistance to cefuroxime was uncommon and resistance to ceftazidime or cefotaxime was confined to five isolates of Enterobacter cloacae (four of which were from patients who had been previously treated with beta-lactams). In only two cases did initially cefuroxime-sensitive strains unambiguously develop resistance during treatment (one strain each of Enterobacter aerogenes and Citrobacter freundii--both treated with amoxycillin).
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The in-vitro activity of ciprofloxacin , a new 4-quinolone, was compared with that of norfloxacin and nalidixic acid against recent clinical isolates of medically important bacteria. Overall, ciprofloxacin and norfloxacin had similar spectra of activity, but ciprofloxacin had somewhat greater intrinsic activity against most organisms. Minimum inhibitory concentrations (MIC) were in the range 0.004-4 mg/l for Enterobacteriaceae, 0.016-2 mg/l for Pseudomonas spp., 0.004-1 mg/l for Acinetobacter, 0.004-0.016 mg/l for Haemophilus influenzae, 0.001-0.004 for gonococci, 0.004-0.03 mg/l for Cmpylobacter , 0.12-2 mg/l for staphylococci, 0.25-4 mg/l for streptococci, 1-32 mg/l for the Bacteroides fragilis group and mostly in the range 0.25-8 mg/l for other obligate anaerobes. Resistant variants could be selected readily in vitro by culture on any of the three compounds investigated. However, while the MICs of nalidixic acid were high for these variants those of ciprofloxacin and norfloxacin were much lower.
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Mouse spleen cells and a murine T cell hybridoma, FS6 14.13.1, produce a glucosteroid response-modifying factor (GRMFT) after stimulation with concanavalin A. GRMFT blocks glucosteroid suppression of helper T cell function and the growth of granulocyte/macrophage progenitor cells in vitro. IL 1 also protects helper T cells and myeloid precursors from glucosteroid suppression. This suggests that GRMFT and IL 1 act congruently to ensure that an effective immune response is generated when endogenous glucosteroid levels are elevated. To understand the role of GRMFT in normal immune responses and in disease states characterized by imbalances in the immune system, we began to purify and characterize GRMFT. GRMFT appears to be distinct from other well-characterized T cell-derived factors. GRMFT is larger than IL 2 as determined by gel exclusion chromatography and is completely separated from IL 2 by isoelectric focusing. Furthermore, purified IL 2 does not have GRMFT activity. Purified IL 3 also lacks GRMFT activity, and conditions that inactivate immune interferon have no effect on GRMFT. Thus, GRMFT is different from IL 2, IL 3, and immune interferon. GRMFT also lacks activity in the thymocyte co-mitogenic assay and is therefore different from IL 1. Finally, FS6 14.13.1 reportedly does not produce TRF or CSF, which suggests that GRMFT is different from these molecules as well.
An infant who received multiple blood transfusions in the neonatal intensive care unit developed a transfusion-associated CMV infection at age 11 weeks and thereafter was noted to have hepatosplenomegaly, mitogen hyporesponsiveness, persistent viruria, an abnormal distribution of T-lymphocyte subpopulations, and poor growth. He has had recurrent opportunistic infections, including Pneumocystis carinii pneumonia. Six donors of blood products received by this infant were investigated; one was found to have chronic lymphadenopathy, weight loss, intermittent diarrhea, lymphopenia, and a profound depression of lymphocytes with a helper/inducer surface phenotype (T4 positive). Family members have an abnormal distribution of T cell subpopulations similar to those reported in asymptomatic homosexuals. The course of disease in our patient suggests that acquired immune deficiency syndrome may be transmitted to young infants via blood products.
The in-vitro antibacterial activity of cefotetan was assessed against recent clinical isolates of common bacteria and also against reference strains that produced known beta-lactamases. The compound was active against most staphylococci (MICs 4 to 8 mg/l) though methicillin-resistant strains were less sensitive. It was also generally active against streptococci (MICs mostly in the range 1 to 16 mg/l). However, enterococci and penicillin-resistant pneumococci were resistant. Cefotetan was highly active against enterobacteria, with 75% of isolates inhibited by 0.5 mg/l and 90% inhibited by 4 mg/l. It was also highly active against Haemophilus influenzae (MICs 0.5 to 4 mg/l) and Neisseria gonorrhoeae (MICs 0.06 to 2 mg/l) but had relatively poor activity against Acinetobacter spp. (MICs mostly 4 to 128 mg/l). Cefotetan had little useful activity against Pseudomonas aeruginosa (MICs 16 to 512 mg/l) but was more active against most other pseudomonads. Cefotetan had moderate activity against the Bacteroides fragilis group (MICs mostly less than or equal to 32 mg/l), though Bact. fragilis sensu stricto and Bact. vulgatus were more sensitive (MICs usually less than or equal to 4 mg/l). It was more active against most other anaerobes, though its activity was always exceeded by that of ampicillin. Cefotetan possessed a high degree of resistance to both plasmid-mediated and chromosomally-determined beta-lactamases.
Pseudomonas aeruginosa isolated from two patients with empyema and one with bronchopneumonia became less sensitive after treatment with ceftazidime, while Ps. aeruginosa persisted in a patient with an infected compound fracture of the tibia treated with ceftazidime but did not become less sensitive. The reduction in sensitivity to ceftazidime, which was small, was accompanied by resistance to azlocillin but there are little reduction in sensitivity to carbenicillin. The resistant strains produced increased amounts of the chromosomally-mediated cephalosporinase produced by most isolates of Ps. aeruginosa. Variants with reduced sensitivity to ceftazidime, which resembled those that developed in vivo, were selected in vitro from each of the initial ceftazidime-sensitive isolates.
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