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Biomedical subjects

C Reid

Publications and source records attributed to C Reid.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prevention by a silymarin/phospholipid compound of ethanol-induced social learning deficits in rats.

We explored the possibility that silymarin (SY), a fraction from Silybum marianum, might protect against the effects of in utero exposure to ethanol upon subsequent social memory function. Three groups of 8 pregnant female Sprague-Dawley rats each were provided with a liquid diet containing 35% ethanol derived calories (EDC). One experimental group received a daily subcutaneous injection of 400 mg/kg SY, the second, a 400 mg/kg oral dose of SY, a third group was maintained on the 35% EDC diet. A fourth group served as the pair-fed control group. The liquid diet regimen was maintained throughout pregnancy. Rats pups were fostered by dams in a fifth group that had been maintained on rat chow. At 90 days the pups were tested for social memory. Social recognition scores recorded for the ethanol pups were significantly poorer than those observed in both SY/ethanol groups and the chow group.

Animals↗
PubMed1999

Aortic rupture as a result of low velocity crush.

A case of aortic disruption in a 35 year old lorry driver is described. This occurred as a result of a low velocity crushing force. Clinicians should be aware that this mechanism of injury may result in aortic disruption as well as the more commonly mentioned severe deceleration force.

Abdominal Injuries↗
PubMed1999

Renal chloride channel, CLCN5, mutations in Dent's disease.

Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer from rickets and other features of the renal Fanconi Syndrome. Patients may have mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are likely to result in a functional loss. Thus, our findings expand the spectrum of CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.

Amino Acid Sequence↗
PubMed1998

The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors.

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.

Binding Sites↗
PubMed1998

Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.

BACKGROUND: Recent clinical trials have demonstrated that HIV protease inhibitors are useful in the treatment of AIDS. It is necessary, however, to use HIV protease inhibitors in combination with other antiviral agents to inhibit the development of resistance. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV protease inhibitors with superior pharmacokinetic and efficacy profiles. In our attempts to design and select improved cyclic urea HIV protease inhibitors, we have simultaneously optimized potency, resistance profile, protein binding and oral bioavailability. RESULTS: We have discovered that nonsymmetrical cyclic ureas containing a 3-aminoindazole P2 group are potent inhibitors of HIV protease with excellent oral bioavailability. Furthermore, the 3-aminoindazole group forms four hydrogen bonds with the enzyme and imparts a good resistance profile. The nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851 were selected as our next generation of cyclic urea HIV protease inhibitors because they achieve 8 h trough blood levels in dog, with a 10 mg/kg dose, at or above the protein-binding-adjusted IC90 value for the worst single mutant--that containing the Ile84-->Val mutation. CONCLUSIONS: In selecting our next generation of cyclic urea HIV protease inhibitors, we established a rigorous set of criteria designed to maximize chances for a sustained antiviral effect in HIV-infected individuals. As DMP 850 and DMP 851 provide plasma levels of free drug that are sufficient to inhibit wild-type HIV and several mutant forms of HIV, they could show improved ability to decrease viral load for clinically significant time periods. The ultimate success of DMP 850 and DMP 851 in clinical trials might depend on achieving or exceeding the oral bioavailability seen in dog.

Animals↗
PubMed1998

Covert manipulation of energy density of high carbohydrate diets in 'pseudo free-living' humans.

OBJECTIVE: This study examined the effects of varying the energy density (ED) of high carbohydrate (HC) diets on food and energy intake (EI), subjective hunger and body weight in humans. DESIGN: Randomised cross-over design. Subjects were each studied twice during 14 d, throughout which they had ad libitum access to one of two covertly-manipulated diets. SUBJECTS AND METHODS: Six healthy men (mean age (s.d.)=32.17 y s.d. (5.26 y), mean weight=69.74 kg s.d. (2.75 kg), mean height=1.76 m s.d. (0.05 m), body mass index (BMI)=22.57 (2.2) kg/m2) were studied. The fat, carbohydrate (CHO) and protein content (as % energy) and ED of each diet were 21:66:13% and 357 kJ/100 g, (low-energy density (LED)) or 22:66:12% and 629 kJ/100 g (high-energy density (HED)). A medium fat diet was provided at maintenance (1.6 x BMR, MF for 2 d) before each ad libitum period. Subjects could alter the amount, but not the composition of foods eaten. RESULTS: Mean EI was 8.67 and 14.82 MJ/d on the LED and HED diets, respectively. Subjects felt significantly more hungry on the LED diet, than on the HED diet (F(1,160)38.28; P < 0.001) and found the diets to be similarly pleasant (72.72 mm vs 71.54 mm (F(1,392)0.31; P = 0.579)). Mean body weight decreased on the LED diet at a rate of 0.1 kg/d and increased at 0.06 kg/d on the HED diet (F(1,131)86.60; P < 0.001), giving total weight changes of -1.41 kg and +0.84 kg, respectively, both of which were significantly different from zero (P < 0.01). CONCLUSION: Excess EI is possible on HC, HED diets, at least under conditions where diet selection is precluded. Comparison of these results with previous studies, which altered ED using fat, suggests that CHO may be a better cue for hunger than fat.

Adult↗
PubMed1998

The effect of covertly manipulating the energy density of mixed diets on ad libitum food intake in 'pseudo free-living' humans.

OBJECTIVE: This study examined the effects of covert alterations in the energy density (ED) of mixed, medium fat (MF) diets on ad libitum food and energy intake (EI), subjective hunger and body weight in humans. DESIGN: Randomised cross-over design. Subjects were each studied three times (factorial design), during 14d, throughout which they had ad libitum access to one of three covertly-manipulated MF diets. SUBJECTS: Six healthy men, mean age (s.e.m.) = 30.0 y (12.76 y), mean weight = 71.67 kg (19.80 kg); mean height = 1.79 m (0.22 m), body mass index (BMI) = 22.36 (2.60) kg/m2, were studied. The fat, carbohydrate (CHO) and protein in each diet (as a proportion of the total energy) and energy density (ED) were, low-ED (LED), 38:49:13%; 373 kJ/100 g; medium-ED (MED), 40:47:13%; 549 kJ/100 g; high-ED (HED), 39:48:13%; 737 kJ/100 g. Subjects could alter the amount but not the composition of foods eaten. They were resident in (but not confined to) a metabolic suite throughout the study. RESULTS: Solid food intake decreased as ED increased, giving mean values of 2.84, 2.51 and 2.31 kg/d, respectively. This was insufficient to defend energy balance, since energy intake increased with increasing ED (F(2,10) 16.08; P < 0.001) giving mean intakes of 10.12, 12.80 and 16.17 MJ/d, respectively. Rated pleasantness of food (measured on visual analogue scales) was not significantly different between diets nor was subjective hunger different between the LED, MED and HED diets, respectively. Diet significantly affected body weight (F(2,10) = 4.62; P = 0.038), producing changes of -1.20, 0.02 and 0.95 kg, respectively, by day 14. CONCLUSION: Dietary ED can influence EI and body weight, since changes in amount eaten alone are insufficient to defend energy balance, when subjects feed on unfamiliar diets and diet selection is precluded. Comparison with our previous studies suggest that there was compensation in solid food intake when ED was altered using mixed diets (as in this study) compared to previous studies which primarily used fat or CHO to alter dietary ED.

Adult↗
PubMed1998

The prevalence of isolated systolic hypertension in patients 60 years of age and over attending Australian general practitioners.

AIMS: To determine the prevalence of isolated systolic hypertension (ISH) in patients 60 years of age and over attending general practitioners, and the proportion of patients in whom blood pressure (BP) remains within the ISH range when measured on three successive occasions and when using home BP monitoring. METHODS: BP was measured in 38 832 patients. Patients categorized as having ISH were reviewed after one week. Patients who had BPs in the ISH range at the second visit were provided with a home BP monitor and attended again in one week's time for further clinic blood pressure measurements. RESULTS: 8.6% of all patients were classified as having ISH and 31.4% as having borderline ISH at the first clinic visit. ISH was twice as prevalent in patients receiving antihypertensive therapy (12.4%) than in those not on antihypertensive therapy (6.2%). Of the patients initially categorized as having ISH, and who attended all three clinic visits and completed the home BP monitoring, 52.3% were confirmed as having ISH, 34.0% fell into the borderline ISH range and only 7.0% had a normal BP reading at the third clinic visit. The use of home BP monitoring produced similar results. CONCLUSION: ISH is present on first screening in approximately 8% of elderly Australian patients. This prevalence falls by about 50% when BP is measured on two further occasions, with most patients subsequently falling into the borderline ISH range. Home BP monitoring does not reduce the percentage of patients classified as having ISH on the basis of three clinic measurements.

Age Factors↗
PubMed1998

Continuing medical education one year on--how was it for me?

Over the period of a year I have systematically recorded any episodes of continuing medical education (CME) that I have attended, and reflect on the effectiveness of this system in terms of whether it has achieved its objective, that is, has my behaviour changed, and whether the existence of the need to record CME has influenced this effect. I consider which aspects of CME have been most beneficial. I conclude that the proposed level of CME is readily achievable, useful, but costly. The way in which I learn most or best is in preparing presentations or teaching sessions. There has been some debate on the usefulness of keeping a record of CME to which I would like to add my opinion. I also recommend the form of record keeping I have used as an impetus to reflection and research on the topic of education received, as this reinforces and enhances the educational experience.

Education, Medical, Continuing↗