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Biomedical subjects

B A Hamilton

Publications and source records attributed to B A Hamilton.

27 records · Page 2Linked to original sources

A pharmacokinetic and pharmacodynamic comparison of plain and enteric-coated prednisolone tablets.

1. Eight healthy volunteers and eight patients suffering from chronic obstructive pulmonary disease (COPD) received 30 mg prednisolone as plain (P) and enteric-coated tablets (EP) in a randomised, cross-over manner. Plasma prednisolone and cortisol and blood glucose were measured over 24 h. 2. Although absorption of prednisolone was considerably slower when administered as the enteric-coated form, peak plasma drug concentrations and total AUC (0,24 h) were equivalent for the two formulations. Malabsorption of prednisolone was not observed. 3. The administration of EP was associated with significantly less adrenal suppression in volunteers than P as judged by measurement of AUC (0,24 h) values for endogenous cortisol. However, this difference did not reach statistical significance in the patient group. 4. Plasma cortisol concentrations declined more slowly following administration of the enteric-coated form to both groups. The difference in time taken (median and range) to maximum suppression of cortisol was statistically significant (P less than 0.05) between P (2.5 h; 2-4 h) and EP (4 h; 3-12 h) preparations administered to volunteers. There was a similar significant difference (P less than 0.05) between P (2.5 h; 1-4 h) and EP (7 h; 2-12 h) in the patients. 5. Plasma cortisol concentrations were significantly lower at 24 h in patients receiving the enteric-coated product in association with higher terminal prednisolone concentrations. 6. Blood glucose concentrations increased over an 8 h period in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Large scale screen for transposon insertions into cloned genes.

We describe a method of screening for transposon insertions in or near Drosophila loci that correspond to cloned DNA sequences. We mobilize a modified P element transposon that carries a bacterial plasmid origin of replication and a drug-resistance marker. The genomic sequences flanking each transposon insertion site can then be rescued as a plasmid in Escherichia coli. Libraries of such plasmids, representing pools of transposon-mutagenized individuals, are used as hybridization probes against cloned sequences to determine whether a transposon has inserted next to a particular site in the genome. The number of loci that can be screened simultaneously by this procedure is quite large. We have screened an array of cDNA clones representing almost 700 distinct loci against libraries representing 760 mutagenized flies, and we obtained hybridization signals to 7 different cDNAs. Three of these events have been analyzed in detail and represent genuine insertions near genomic sequences that correspond to the cDNAs.

Animals↗

Transposon-facilitated DNA sequencing.

We describe here a transposon-based DNA sequencing strategy that allows the introduction of sequencing priming sites throughout a target sequence by bacterial mating. A miniplasmid was designed to select against transposon insertions into the vector. Sites of transposon insertion are mapped by the polymerase chain reaction with bacterial overnight cultures providing the templates. A small set of plasmids with transposons spaced several hundred base pairs apart can then be sequenced. Sequencing primers corresponding to the transposon ends allow sequencing in both directions. Thus, the entire sequence of both strands can be easily determined.

Base Sequence↗

Phage lambda cDNA cloning vectors for subtractive hybridization, fusion-protein synthesis and Cre-loxP automatic plasmid subcloning.

We describe the construction and use of two classes of cDNA cloning vectors. The first class comprises the lambda EXLX(+) and lambda EXLX(-) vectors that can be used for the expression in Escherichia coli of proteins encoded by cDNA inserts. This is achieved by the fusion of cDNA open reading frames to the T7 gene 10 promoter and protein-coding sequences. The second class, the lambda SHLX vectors, allows the generation of large amounts of single-stranded DNA or synthetic cRNA that can be used in subtractive hybridization procedures. Both classes of vectors are designed to allow directional cDNA cloning with non-enzymatic protection of internal restriction sites. In addition, they are designed to facilitate conversion from phage lambda to plasmid clones using a genetic method based on the bacteriophage P1 site-specific recombination system; we refer to this as automatic Cre-loxP plasmid subcloning. The phage lambda arms, lambda LOX, used in the construction of these vectors have unique restriction sites positioned between the two loxP sites. Insertion of a specialized plasmid between these sites will convert it into a phage lambda cDNA cloning vector with automatic plasmid subcloning capability.

Bacteriophage lambda↗

Depression in general practice: a comparison of flupenthixol dihydrochloride and dothiepin hydrochloride.

A single-blind, parallel group, general practice study was carried out in 153 patients with mild to moderate depression to compare the efficacy and tolerability of flupenthixol dihydrochloride and dothiepin hydrochloride. Patients were allocated at random to receive single daily doses of either 1 mg flupenthixol in the morning or 75 mg dothiepin in the evening, and this dose could be doubled at the end of 2 weeks in the event of inadequate response. Assessments were made on entry and after 1, 2, 4 and 6 weeks of treatment using the Hamilton Depression Rating Scale, a 4-point severity scale and an unwanted symptoms checklist. The results showed that both treatments significantly improved the patients' condition over 6 weeks, and there was a significant difference in favour of flupenthixol at end-point. Both drugs were well tolerated, although persistence of anticholinergic side-effects in the dothiepin group resulted in a trend favouring flupenthixol. One patient in the flupenthixol group attempted suicide by overdose but made a complete recovery.

Adolescent↗

Flupenthixol and fluvoxamine in mild to moderate depression: a comparison in general practice.

Seventy-two depressed patients attending general practices were randomly allocated to treatment with either flupenthixol dihydrochloride (1 to 2 mg/day) or fluvoxamine maleate (100 to 200 mg/day) to assess efficacy and side-effects over a 4-week period. Clinical assessments were carried out before medication (Day 1) and on Days 8, 15 and 29 of treatment using the Hamilton Rating Scale for Depression, Clinical Global Impressions (CGI) and a patient self-assessment visual analogue scale for depression. Unwanted symptoms were also recorded. Reduction in mean total scores on the Hamilton scale at each assessment and therapeutic effect improvement on the CGI were greater for patients treated with flupenthixol (p less than 0.05). Reduction in unwanted symptoms was progressive in both groups, but more pronounced in patients receiving flupenthixol. Twice as many new symptoms arose in the fluvoxamine group compared to the flupenthixol group. Four patients were withdrawn in the fluvoxamine group due to untoward drug effects compared with none in the flupenthixol group.

Adolescent↗

Low release of selenium from recovered ruminal pellets.

The effectiveness of selenium pellets in grazing Merino sheep was examined by comparing the selenium status of treated and untreated animals over a 13 month period. The selenium status of treated sheep, as measured by blood glutathione peroxidase levels, had reached a maximum 3 months after treatment and there was a marked decline between 5 and 13 months. All pellets were recovered from treated sheep at slaughter this confirmed that the observed decline was not due to a loss of pellets. In a separate study sheep were slaughtered 14 months after treatment and some of the recovered pellets were readministered to sheep maintained on a low selenium diet. The selenium status of the sheep receiving recovered pellets remained low. This bioassay technique indicated that there was little available selenium released from these pellets. The selenium status of sheep given previously unused pellets was declining after 18 weeks.

Animals↗