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Biomedical subjects

D L Browne

Publications and source records attributed to D L Browne.

At least 19 recordsLinked to original sources

What do patients with diabetes know about their tablets?

AIMS: To assess knowledge about oral hypoglycaemic agents amongst patients with diabetes and non-specialist healthcare professionals. METHOD: An anonymous questionnaire was used in two centres to assess knowledge about oral agents amongst 261 patients with Type 2 diabetes mellitus (mean age 64 years) and 102 health professionals (including doctors, nurses and pharmacists). RESULTS: Only 15% of patients knew the correct mechanism of action of their medication and 62% took tablets correctly in relation to food. Only 10% of those taking a sulphonylurea knew it may cause hypoglycaemia and 20% of those taking metformin were aware of its gastrointestinal side-effects. Twenty per cent forgot to take their tablets at least once a week and 5% omitted tablets because of hyperglycaemia. Only 35% of patients recalled receiving advice about their medication with only 1% receiving written advice. The healthcare professionals showed important gaps in their knowledge on dosage timing and mechanism of action, particularly with respect to metformin and acarbose. CONCLUSION: It is concluded that patients' and professionals' knowledge of oral hypoglycaemic agents is poor. More appropriate advice and information to patients from prescribers may improve patient understanding and hence compliance. Community pharmacists are ideally placed to reinforce this information.

Acarbose↗

Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.

OBJECTIVE: Studies examining vasodilatory responses to acetylcholine (ACh) and its derivatives have been conflicting. Enhanced activation of the cyclo-oxygenase pathway and increased availability of vasodilatory prostanoids may occur in type 1 diabetes, and this may compensate for the observed reduction in nitric oxide (NO) activity We examined the role of cyclo-oxygenase inhibition on vasodilatory responses in 12 healthy normotensive type 1 diabetic adults and 12 nondiabetic control subjects of similar age, sex, and BMI. RESEARCH DESIGN AND METHODS: Forearm blood flow was measured using a venous occlusion plethysmography technique at baseline and after brachial artery infusions of ACh (7.5, 15, and 30 microg/min). Forearm blood flow at baseline and after ACh was then reexamined after local intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm volume), a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (2.65 +/- 0.26 vs. 2.59 +/- 0.20 ml/min per 100 ml, respectively; P = 0.4). After indomethacin infusion, the vasodilatory responses to all doses of ACh were reduced in both the diabetic (by 25.30 +/- 4.90%) and control group (by 11.23 +/- 5.45%). However, the reduction in blood flow response to ACh after indomethacin was greater in diabetic patients compared with control subjects (P = 0.03). CONCLUSIONS: Our findings suggest that vasodilatory, prostanoids are important in determining endothelial response to ACh in diabetic and nondiabetic subjects. Increased prostaglandin-mediated vasodilation may compensate for attenuated responses to NO previously reported in diabetic subjects. These findings may partly explain the conflicting reports of endothelial dysfunction in patients with type 1 diabetes.

Acetylcholine↗

Hereditary myokymia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide.

A sixth family with autosomal dominantly inherited myokymia and paroxysmal ataxia is described. The syndrome in this family is linked to the recently discovered locus for inherited myokymia and paroxysmal ataxia on the human chromosome 12p, and a missense mutation is shown in the KCNA1 gene. The attacks of ataxia in this family compare well with those of previously described families and similarly are precipitated by kinesigenic stimuli, exertion, and startle. Responsiveness of these attacks to low dose acetazolamide is confirmed, but some loss of efficacy occurs with prolonged treatment, and side effects are notable. Although not all affected family members showed myokymia on clinical examination, electromyography invariably showed myokymic discharges, in one patient only after a short provocation with regional ischaemia. One affected family member also had attacks of paroxysmal kinesigenic choreoathetosis, responsive to carbamazepine.

Acetazolamide↗

Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene.

Amino Acid Sequence↗

The gene encoding chicken chromosomal protein HMG-14a is transcribed into multiple mRNAs.

The sequence and structure of the chicken HMG14a gene encoding HMG-14a non-histone chromosomal protein suggest that it may be a unique member of the HMG (high mobility group) gene family with properties intermediate to those of the typical HMG-14 and HMG-17 genes. Genomic clones were isolated which together contain the complete chicken HMG-14a gene. The gene covers about 10 kb while coding for an mRNA of about 1000 nt in size. Primer extension, S1 mapping and further cDNA clone analysis suggest that HMG-14a codes for multiple mRNAs arising from two or more transcription start points with alternative splicing and utilization of two or more polyadenylation sites. However, no variation in the coding portion of the mRNA has been observed. The sequence of the promoter region of HMG-14a is similar to that of chicken HMG-14b and human HMG-14 in that it is very G+C rich, contains several putative Sp1-binding sequences and has an unusually high density of CpG dinucleotides. Expression studies confirm earlier results suggesting that the gene is expressed at low levels in most tissue types.

Alternative Splicing↗