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D G Roberts

Publications and source records attributed to D G Roberts.

25 records · Page 2Linked to original sources

Evaluation of oral and low dose intravenous prostaglandin E2 in management of ductus dependent congenital heart disease.

Prostaglandin E2 was given orally to 59 infants with ductus dependent congenital heart disease, and intravenous infusions were substituted for varying periods in 27 of them. An additional three neonates received intravenous treatment alone. Mean oral maintenance dose was 27 micrograms/kg per hour and the mean intravenous dose was 0.005 micrograms/kg per minute. Mean duration of treatment was 49 days (range 16 hours to 272 days). Oral treatment was almost always effective and was especially suitable for long term use. Low dose intravenous treatment was readily substituted when indicated. Complications were usually 'minor'. Growth of the infants and of their pulmonary arteries facilitated later surgical management.

Administration, Oral↗

Effect of sustained water diuresis on prostaglandin E2 excretion in humans.

The relationship of the renal excretion of prostaglandin E2 (PGE2) to urine flow during a water diuresis was examined using radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS). Seven normal women fasted overnight were water loaded with 20 ml/kg orally, and each hour for 3 h they drank water to replace the urine volume plus 20 ml. The osmolality of the collected urines ranged from 49 to 1,073 mosmol/kg. Assay of urinary PGE2 concentrations by both RIA and GC-MS gave a correlation coefficient of 0.94. Eight normal women were then studied with a water diuresis sustained for 6 h. The excretion of PGE2 (measured with the validated RIA) increased for the 1st 2-3 h (from 1.8 +/- 0.5 to 25.8 +/- 16.6 pg X kg-1 X min-1), but then fell to base-line level by the 5th h (to 2.9 +/- 0.8 pg X kg-1 X min-1) even though the water diuresis was sustained. The urinary concentration vs. time curves for PGE2 and for the freely diffusible solute urea were compared. PGE2 concentration remained elevated for 3 h before falling (from the 100 pg/ml range to 15 pg/ml) while urea concentration decreased steadily from the 1st h. This finding suggests that the early urinary PGE2 excretion was not a washout phenomenon and is consistent with a transient increase in PGE2 synthesis. We conclude that urinary excretion of PGE2 is not a simple function of urine flow after a water load. There is a transient initial increase in urinary PGE2 excretion at the start of a water load that probably reflects an increase in renal PGE2 synthesis. However, with a sustained water diuresis, PGE2 excretion falls, indicating that an enhanced PGE2 synthesis rate is not required to sustain a water diuresis.

Adult↗

Adenine phosphoribosyltransferase mutants in Saccharomyces cerevisiae.

Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase (A-PRT, EC 2,4,2,7) have been isolated following selection for resistance to 8-azaadenine in a prototrophic strain carrying the ade4-su allele of the gene coding for amidophosphoribosyltransferase (EC 2,4,2,14). The mutants were recessive and defined a single gene, apt1. They did not excrete purine when combined with ade4+. The mutants appeared to retain some A-PRT activity in crude extracts, and strains of the genotype ade2 apt1 responded to both adenine and hypoxanthine. Mutants deficient in adenine aminohydrolase (EC 3,5,4,2) activity, aah1, and hypoxanthine:guanine phosphoribosyltransferase (EC 2,4,2,8) activity, hpt1, were used to synthesize the genotypes apt1 hpt1 aah+ and apt1 hpt+ aah1. The absence of A-PRT activity in strains with these genotypes confirmed the hypothesis that the residual A-PRT activity of apt1 mutants was due to adenine aminohydrolase and hypoxanthine:guanine phosphoribosyltransferase acting in concert.

Adenine Phosphoribosyltransferase↗

Hypoxanthine: guanine phosphoribosyltransferase mutants in Saccharomyces cerevisiae.

Yeast mutants lacking activity of the enzyme hypoxanthine:guanine phosphoribosyltransferase (H:G-PRT) have been isolated by selecting for resistance to 8-azaguanine in a strain carrying the wild type allele, ade4%, of the gene coding for amidophosphoribosyltransferase (PRPPAT), the first enzyme of de novo purine synthesis. The mutants excrete purines and are cross-resistant to 8-azaadenine. They are recessive and represent a single complementation group, designated hpt1. Ade4-su, a prototrophic allele of ade4 with reduced activity of PRPPAT, is epistatic to hpt1, suppressing purine excretion and resistance to azaadenine but not resistance to azaguanine. The genotype ade2hpt1 does not respond to hypoxanthine. Hpt1 complements and is not closely linked to the purine excreting mutants pur1 to pur5. Hpt1 and pur6, a regultory mutant of PRPPAT, are also unlinked but do not complement, suggesting a protein-protein interaction between H:G-PRT and PRPPAT. Mycophenolic acid (MPA), an inhibitor of de novo guanine nucleotide synthesis, inhibits the growth of hpt1 and hpt1+. Xanthine allows both genotypes to grow in the presence of MPA whereas guanine only allows growth of hpt1+. Activity of A-PRT, X-PRT and H:G-PRT is present in hpt+. Hpt1 lacks activity of H:G-PRT but has normal A-PRT and X-PRT.

Alleles↗

Comparison between cefotaxime and a combination of benzylpenicillin and cloxacillin as an antibiotic prophylaxis in cardiac surgery with cardio-pulmonary bypass.

In a prospective randomized trial, 422 patients undergoing elective cardiac surgery with cardiopulmonary bypass were studied for comparing two types of prophylactic antibiotic treatment. One group, 204 patients, received 4 doses of cefotaxime for 2 days. The other group, 198 patients, received 6 doses of benzylpenicillin combined with cloxacillin for 3 days. Sixty percent received the planned cefotaxime prophylaxis (CTX), while 43.4% received the planned combined benzylpenicillin with cloxacillin prophylaxis (BPC). This was because several patients in both groups required additional antibiotics for treatment of high fever (39.7%, CTX-ADD, in the cefotaxime group compared to 56.6%, BPC-ADD in the other group (p less than 0.01). The overall infection rate in the groups receiving the planned prophylaxis was significantly lower (4.1%) in the CTX-group compared to the 14% in the BPC-group (p less than 0.05). Early infections (less than 14 days) were lower in the groups CTX-group (3%) compared to the BPC-group (16%) (p less than 0.046). In the groups receiving additional antibiotics for fever (CTX-ADD and BPC-ADD), the former had a significantly lower number of infections, 16 compared to 23, in the latter group (p less than 0.01). There were significantly fewer early infections in the CTX-ADD compared to the BPC-ADD group (4 vs. 10 respectively, p less than 0.01). No deep infections were seen when CTX or CTX-ADD was used, while 6 deep wound infections occurred when BPC or BPC-ADD was used. The lowest rate of positive cultures of bacteria was seen in the CTX-group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗