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Biomedical subjects

A King

Publications and source records attributed to A King.

At least 379 records · Page 21Linked to original sources
PubMed1987

Characterisation of cDNA clones for hypoxanthine-guanine phosphoribosyltransferase from the human malarial parasite, Plasmodium falciparum: comparisons to the mammalian gene and protein.

The isolation of cDNA clones for hypoxanthine-guanine phosphoribosyltransferase (HPRT) from the human malarial parasite, Plasmodium falciparum, is described. Northern analysis indicates that P. falciparum HPRT mRNA is the same size as that coding for mammalian HPRT. The predicted amino acid sequence of the P. falciparum HPRT protein shows extensive homology to the mammalian enzyme. Homology between the two proteins occurs in distinct blocks and a putative catalytic binding domain in the centre of the protein is also conserved. Five out of the seven characterised mammalian HPRT missense mutations map to regions which are conserved in the P. falciparum protein.

Amino Acid Sequence↗
PubMed1987

Randomized trial of the addition of cis-platin (DDP) and/or BCG to cyclophosphamide (CTX) chemotherapy for ovarian carcinoma.

A prospective randomized trial has compared cyclophosphamide (CTX) with CTX plus cis-diamminodichloroplatinum (DDP) as the initial chemotherapy for advanced ovarian carcinoma. A secondary randomization compared the addition of BCG treatment to either chemotherapy. The addition of DDP had no measurable impact on survival, but a small survival trend favoring BCG-treated patients was noted (P less than 0.08). Toxicity from BCG treatment was insignificant, but the addition of DDP increased both early nausea and vomiting and later hematologic toxicity. There were three long-term complete remission patients, and these all came from the group of six patients with pretreatment residual disease less than 2 cm. A univariate analysis of pretreatment prognostic factors indicated significantly better prognosis (P less than 0.02) for patients with no palpable tumor, platelet count less than 400,000/mm3, residual tumor less than 2 cm, resting pulse less than 91/min. and LDH less than 250 U/L. The authors conclude that for patients with large (greater than 2 cm) residual disease, there is no compelling evidence that initial combination therapy is superior to aggressive single alkylating agent treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Left anterior fascicular block and masking of inferior wall infarction.

A case of inferior wall myocardial infarction that was obscured by left anterior hemiblock is presented. This report illustrates that changes in the sequence of electrical activation of the left ventricle resulting from this conduction disturbance may lead to a missed electrocardiographic diagnosis.

Electrocardiography↗
PubMed1987

Bridging markers defining the map position of X linked hypophosphataemic rickets.

Hypophosphataemic rickets is commonly an X linked dominant hereditary disorder associated with a renal tubular defect in phosphate transport and bone deformities. The gene causing this disorder has been mapped to Xp22.31----p21.3 by using cloned human X chromosome sequences identifying restriction fragment length polymorphisms (RFLPs) in linkage studies of affected families. The hypophosphataemic rickets gene locus (HPDR) was previously mapped distal to the X linked polymorphic locus DXS41 (99.6) but its position in relation to the distal loci DXS43 (D2) and DXS85 (782) was not established. In order to obtain a precise mapping of the disease locus in relation to these genetic loci, additional affected families informative for these X linked markers have been investigated. The combined results from the two studies have established linkage with the loci DXS41 (99.6) and DXS43 (D2); peak lod score for DXS41 (99.6) = 7.35, theta = 0.09, and peak lod score for DXS43 (D2) = 4.77, theta = 0.16. Multilocus linkage analysis mapped the hypophosphataemic rickets gene distal to the DXS41 (99.6) locus and proximal to the DXS43 (D2) locus, thereby revealing two bridging genetic markers for the disease.

Chromosome Mapping↗
PubMed1987

The in-vitro activity of roxithromycin, a new macrolide antibiotic, in comparison with that of erythromycin.

A study was made of the in-vitro activity of roxithromycin in comparison with that of erythromycin on selected recent clinical isolates of a wide range of organisms. Minimum inhibitory concentrations (MICs) were determined by an agar dilution method with an inoculum of 10(4) cfu. Minimum bactericidal concentrations (MBCs) and the effect of pH were determined by a broth dilution method on selected strains. In general the in-vitro activity of roxithromycin mirrored that of erythromycin, but it was slightly less active. Most strains of streptococci, with the exception of enterococci, were highly sensitive to roxithromycin, as were isolates of Gardnerella vaginalis. Branhamella catarrhalis and Neisseria gonorrhoeae. Staphylococci and enterococci were only moderately sensitive to both agents as was Haemophilus influenzae. Most anaerobic bacteria were sensitive although Bacteroides fragilis, fusobacteria and some strains of some clostridial species were moderately resistant. The MBCs were usually at least 16-fold higher than MICs for most staphylococci, enterococci, alpha-haemolytic streptococci and B. fragilis; but for beta-haemolytic streptococci, pneumococci, H. influenzae and B. catarrhalis the MBCs were usually only 2- to 4-fold higher than MICs. Roxithromycin was most active at pH 8 and generally for each unit fall in pH there was a 4-fold diminution of activity. However, the effect was less marked for pneumococci, beta-haemolytic streptococci and H. influenzae.

Anti-Bacterial Agents↗
PubMed1986

Prevalence and mechanisms of aminoglycoside resistance. A ten-year study.

Aminoglycoside resistance was monitored at St. Thomas' Hospital from 1975 to 1984. Gentamicin resistance had appeared in a number of species by 1975, but remained rare (less than 1 percent of isolates) in Escherichia coli throughout the study period. Gentamicin-resistant Klebsielleae had become fairly common (8 percent of isolates) by 1977, but little change has subsequently occurred in their frequency of isolation. Serratia species are not frequently isolated; gentamicin resistance in these organisms was not observed until 1979. Since then, 10 to 20 percent of isolates have been found to be resistant. Except for Providencia, most isolates of which were gentamicin-resistant, less than 5 percent of the Enterobacteriaceae isolated were found to be resistant to gentamicin during the 10-year period. Throughout the study, approximately 5 percent of the Pseudomonas aeruginosa isolates were resistant to gentamicin. Less than 5 percent of the isolates of Acinetobacter were resistant to gentamicin before 1979, at which time 40 percent were found to be resistant; subsequently, gentamicin resistance among these organisms has become somewhat less common. On the whole, tobramycin resistance has mirrored gentamicin resistance. However, before 1979, most gentamicin-resistant Klebsielleae isolates had retained susceptibility to tobramycin, as had most gentamicin-resistant isolates of Acinetobacter and P. aeruginosa. Amikacin resistance has remained very unusual in all organisms, apart from non-aeruginosa Pseudomonas species. Until 1977, nearly all the resistance among Enterobacteriaceae was attributable to AAC(3)-I, except for that caused by AAC(2') production in Providencia and the non-enzymatic resistance observed in E. coli. However, more recently, AAC(3)-II and AAD(2'') have become the most common mechanisms of resistance. The resistance of most gentamicin-resistant isolates of P. aeruginosa from 1974 to 1977 was attributable to non-enzymatic mechanisms; subsequently, such resistance was more often caused by AAC(3)-I, AAC(6'), or AAD(2''). Gentamicin resistance first appeared in Staphylococcus aureus in 1976, after which about 1 to 2 percent of the isolates from hospitalized patients were found to be resistant, mostly because of production of AAC(6') and APH(2'').

Acinetobacter↗
PubMed1986

Linkage studies of X-linked recessive spastic paraplegia using DNA probes.

A family with six males affected by X-linked spastic paraplegia (McKusick No. 31290) is described. The disease was accompanied by mental retardation in all patients (severe in four cases with IQ of 40) and by absence of extensor pollicis longus (in four cases). The following X chromosome DNA probes were used in linkage studies: 782, RC8, 99-6, 754, OTC, L128, pDP34, p43-15, DX13, and St14. The mutation is closely linked to the loci DX13 (DXS15) and St14 (DXS52) (no recombinants in 11 meioses) and therefore localised to the telomeric region of the long arm of the human X chromosome.

Adolescent↗
PubMed1986

Mapping of human X-linked hypophosphataemic rickets by multilocus linkage analysis.

Eleven families with X-linked dominant hypophosphataemic rickets (HPDR) have been typed for a series of X chromosome markers. Linkage with probe 99.6 (DXS41) was demonstrated with a peak lod score of 4.82 at 10% recombination. Multilocus linkage analysis showed that HPDR maps distal to 99.6; this probe has previously been located at Xp22.31-p21.3 by in situ hybridisation. In the mouse hypophosphataemia (Hyp) maps to the distal part of the X chromosome; our location in man is consistent with a scheme which relates the mouse and human X chromosomes by two rearrangements. No marker has yet been found which shows no recombination with HPDR.

Animals↗
PubMed1986

Beta-lactamases with high activity against imipenem and Sch 34343 from Aeromonas hydrophila.

Two groups of inducible beta-lactamases were found among nine isolates of Aeromonas hydrophila. Five isolates produced enzymes with high activity against the penem Sch 34343 and the carbapenem imipenem: the enzymes from some of these isolates also had activity against penicillin, ampicillin, carbenicillin, cephaloridine and cephalexin but one isolate produced an enzyme with no detectable activity against cephalosporins. The other four isolates produced typical 'cephalosporinases' with activity against cephaloridine and cephalexin but not against cefuroxime, cefotaxime, penicillins, imipenem or Sch 34343.

Aeromonas↗
PubMed1986

The comparative in-vitro activity of pefloxacin.

The in-vitro antibacterial activities of pefloxacin, other 4-quinolones and representative beta-lactams and aminoglycosides were assessed by determination of minimum inhibitory concentrations (MICs). Pefloxacin (MICs mostly 0.03-2 mg/l) was highly active against Enterobacteriaceae. Gentamicin had slightly lower activity, and ceftazidime and norfloxacin similar activities to pefloxacin whereas ciprofloxacin was more active. Pefloxacin (MICs 0.03-2 mg/l) was active against Acinetobacter but again ciprofloxacin was more active. Aeromonas was highly susceptible to pefloxacin and norfloxacin (MICs 0.008-0.03 mg/l) as well as to ciprofloxacin (MICs 0.001-0.008 mg/l). Pefloxacin (MICs 1-8 mg/l) had similar activities to ceftazidime and gentamicin against Pseudomonas aeruginosa but tobramycin (MICs 0.25-32 mg/l), norfloxacin (MICs 0.25-4 mg/l) and ciprofloxacin (MICs 0.06-1 mg/l) were generally more active. Haemophilus influenzae was susceptible to pefloxacin (MICs 0.008-0.06 mg/l) and to norfloxacin and ciprofloxacin, all of which were more active than ampicillin or ceftazidime. Gardnerella vaginalis was not very susceptible to pefloxacin (MICs 2-8 mg/l), the other 4-quinolones or gentamicin but ampicillin and ceftazidime were highly active. Neisseria gonorrhoeae was very susceptible to pefloxacin and norfloxacin (MICs 0.016-0.12 mg/l) and ciprofloxacin (MICs 0.002-0.008 mg/l). The activity of pefloxacin (MICs 0.25-1 mg/l) was similar to that of ciprofloxacin (MICs 0.12-2 mg/l) but greater than that of norfloxacin (MICs 0.5-4 mg/l) against Staphylococcus aureus. Vancomycin (MICs 1-2 mg/l) had similar activity in vitro but whilst gentamicin was highly active against some isolates, others were resistant. Pefloxacin (MICs mostly 4-32 mg/l) and the other 4-quinolones had lower activity against streptococci (including alpha-, beta-, and non-haemolytic strains, enterococci and pneumococci) than against staphylococci. Benzylpenicillin (or ampicillin in the case of enterococci) were usually more active than any of the 4-quinolones. Bacteroides species, both of the fragilis and melaninogenicus/oralis groups were generally moderately resistant to pefloxacin (MICs 2-32 mg/l) and norfloxacin though ciprofloxacin was more active. Whilst the activity of pefloxacin and the other 4-quinolones was generally somewhat higher against the other anaerobes, ampicillin generally had greater activity.

Acinetobacter↗
PubMed1986

The in-vitro activity of CI-934 compared with that of other new 4-quinolones and nalidixic acid.

The in-vitro activity of CI-934, a new 4-quinolone compound, was compared with that of the other new 4-quinolones, enoxacin and ciprofloxacin, and also with that of nalidixic acid. CI-934 was more active than any of the other 4-quinolones tested against Gram-positive aerobic organisms including Staphylococcus aureus (MICs 0.06-0.25 mg/l), beta-haemolytic streptococci (MICs 0.12-0.5 mg/l), Streptococcus pneumoniae (MICs 0.25-0.5 ml/l), viridans streptococci (MICs 0.06-0.5 mg/l) and most enterococci (MICs 0.12-0.5 mg/l), although some ampicillin-resistant isolates of Str. faecium were slightly less susceptible (MICs 2 mg/l). All three of the newer 4-quinolones tested were highly active against Enterobacteriaceae, Aeromonas sp., Haemophilus influenzae and Neisseria gonorrhoeae (MICs mostly less than 1 mg/l). The other Gram-negative aerobes tested were in general somewhat less susceptible, although for Acinetobacter and Pseudomonas aeruginosa MICs seldom exceeded 8 mg/l. CI-934 was more active than enoxacin against Gardnerella vaginalis (MICs 1-8 mg/l) although it was a little less active than ciprofloxacin. Bacteroides species (including about half of the fragilis group) were susceptible to CI-934 (MICs mostly 1-8 mg/l): ciprofloxacin had similar activity but enoxacin was less active. Other anaerobes tested were mostly highly susceptible to CI-934 (MICs 1 mg/l or less) but were somewhat less susceptible to enoxacin and ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1986

The comparative in-vitro activity of eight newer quinolones and nalidixic acid.

The in-vitro antibacterial activity of nalidixic acid and the 4-quinolones, ciprofloxacin, norfloxacin, enoxacin, ofloxacin, pefloxacin, A-56619, A-56620 and CI-934 was assessed by determination of MICs. The 4-quinolones were all highly active against most isolates of Enterobacteriaceae, including nalidixic acid-resistant strains. Ciprofloxacin (MICs 0.002-2 mg/l) was the most active and A-56619 (MICs 0.008-32 mg/l) was the least active. A-56619, A-56620, ofloxacin, ciprofloxacin and CI-934 were highly active against Acinetobacter strains, pefloxacin and enoxacin were slightly less active, and a few strains were resistant to norfloxacin. All the compounds, including nalidixic acid, were active against Aeromonas strains (MICs 0.001-0.12 mg/l). Ciprofloxacin (MICs 0.06-1 mg/l) was the most active compound against Pseudomonas aeruginosa; A-56619 and CI-934 (MICs 1-16 mg/l) were the least active against this species. All the compounds were highly active against Haemophilus influenzae, Branhamella catarrhalis and Neisseria gonorrhoeae but the activity of all the compounds was poor against most isolates of Gardnerella vaginalis. All the 4-quinolones were active against staphylococci and CI-934 (MICs 0.03-0.25 mg/l) was the most active. CI-934 (MICs 0.06-2 mg/l) was also the most active compound against all streptococci. Most streptococci were sensitive also to ciprofloxacin (MICs 0.25-4 mg/l) but there were many isolates resistant to the other 4-quinolones. Against the anaerobic bacteria CI-934 was again the most active compound, particularly against the Gram-positive anaerobic cocci. Pefloxacin, enoxacin and norfloxacin had poor activity against most anaerobes. Ofloxacin, ciprofloxacin, A-56619 and A-56620 had good to moderate activity against all species of anaerobes except the Bacteroides fragilis group, against which none of the compounds was very active.

Acinetobacter↗
PubMed1986

Comparison of radiometric and gas capture system for blood cultures.

A single bottle blood culture system that detects the gas produced by micro-organisms from substrates in a specially formulated medium was compared with the Bactec radiometric system. A total of 725 blood samples collected from patients with suspected bacteraemia yielded 75 clinically important isolates. Fifty five (73%) of these cultures were detected by both methods, 16 (21%) by only the Bactec system, and four (5%) by only the Oxoid system. No significant differences were found between the two systems after allowance was made for the different volume of sample inoculated into each system.

Bacteria↗
PubMed1986

Diagnosis of cystic fibrosis in premature infants.

Meconium ileus and pancreatic changes, as described in cystic fibrosis, were found, at autopsy, in a series of six infants who received prolonged neonatal intensive care for prematurity. Cystic fibrosis had not been suspected clinically. These pathological findings are so frequent in sick premature infants, amounting to 12% of all neonatal autopsies conducted over a period of 2 yr in our unit, that we question their specificity for cystic fibrosis and suggest they may be a manifestation of disordered physiology in the severely ill neonate.

Autopsy↗