Self blood glucose monitoring in type 2 diabetes. A financial impact analysis based on UK primary care.

BACKGROUND: UK consensus guidelines recommend limited use of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes using diet and exercise, metformin and/or a glitazone. This analysis quantifies the usage of and costs associated with SMBG in type 2 diabetes according to treatment regimen. METHODS: Prevalence data for diabetes were assessed using UK Quality and Outcomes Framework returns for 2006/2007. Data on current SMBG prescribing expenditure were extracted from UK Prescription Pricing Agency Data for 2007. Prescribing data were extracted from the records of 40,651 patients with diabetes on the IMS Disease Analyzer (MediPlus) database. These were combined to arrive at mean usage and expenditure data per patient, broken down by treatment type. The analysis assumes that it is appropriate to use patients' treatment regimen alone to compare the frequency of SMBG in clinical practice with the frequency recommended in treatment guidelines; it does not take into account other valid reasons for SMBG. RESULTS: Mean national expenditure on SMBG was 73.64 pound sterling per patient per year. Estimated mean weekly test strip usage by treatment was 2.5 (diet), 2.6 (glitazone monotherapy), 3.1 (metformin monotherapy) and 3.5 (sulphonylurea monotherapy). Combination oral therapy ranged from 3.3 to 4.1. Mean annual expenditure in patients with an identified treatment type was 62.06 pound sterling per patient, ranging from 9.83 pound sterling for diet-treated patients to 37.87 pound sterling for those on triple therapy, with insulin-treated patients incurring costs 3-5 times higher. CONCLUSIONS: Based on the assumptions that the treatment regimen is the sole factor in determining the appropriate level of SMBG frequency, this study demonstrates that the use of SMBG exceeds current guidelines in certain treatment groups. The study estimates that the potential savings of up to 17 million pound sterling could be made each year if guidelines were followed more closely. There is a need for further research into SMBG use in patients with type 2 diabetes.

The use of ezetimibe in achieving low density lipoprotein lowering goals in clinical practice: position statement of a United Kingdom consensus panel.

There is no doubt that lowering serum cholesterol levels reduces the risk of major coronary events. This evidence has led treatment guidelines to set progressively lower targets for low density lipoprotein cholesterol (LDL-C). However, despite widespread use of statins, substantial numbers of patients do not achieve the LDL-C goals. Using higher doses of statins in an attempt to achieve these targets may increase the risk of serious adverse effects. Furthermore, the use of combination therapy with agents such as bile acid sequestrants, niacin and fibrates has been limited by increased potential for side effects, drug interactions and poor compliance. Ezetimibe, a selective cholesterol transport inhibitor, reduces the intestinal uptake of cholesterol without affecting absorption of triglycerides or fat-soluble vitamins. In clinical studies, ezetimibe 10 mg, in combination with statins or as monotherapy, was well tolerated and reduced LDL-C by 34-53% and 17-18%, respectively. The available evidence for ezetimibe is reviewed. The role of ezetimibe in increasing the proportion of patients attaining LDL-C treatment goals is discussed.

Cloning of aroG, the gene coding for phospho-2-keto-3-deoxy-heptonate aldolase(phe), in Escherichia coli K-12, and subcloning of the aroG promoter and operator in a promoter-detecting plasmid.

Defective transducing phages carrying aroG, the structural gene for phenylalanine (phe)-inhibitable phospho-2-keto-heptonate aldolase (EC 4.1.2.15; previously known as 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase[phe]), have been isolated, and DNA from two of these phages has been used to construct a restriction map of the region from att lambda to aroG. A 7.6-kb PstI-HindIII fragment from one of these phages was cloned into pBR322 and shown to contain aroG. The location of aroG within the 7.6 kb was established by subcloning and Tn3 transpositional mutagenesis. A fragment carrying the aroG promoter and operator has been cloned into a high copy number promoter-cloning vector (pMC489), and the resulting aroGpo-LacZ' (alpha) fusion subcloned in a low copy number vector. Strains with this fusion on the low copy number vector exhibit negative regulation of beta-galactosidase expression by both phenylalanine and tryptophan and positive regulation by tyrosine in a tyrR+ background.

Peripheral vasoconstriction in patients with sleep related periodic leg movements.

Two patients complaining of insomnia had sleep-related periodic leg movements (nocturnal myoclonus) on polysomnographic evaluation. Both also complained of cold feet and had abnormal peripheral pulse examinations. Treatment with phenoxybenzamine, alpha-adrenergic blocker, normalized the peripheral pulse responses, reduced the complaint of insomnia, and reduced the sleep related leg movements but resulted in only mild sleep improvements. Peripheral pulse examinations of ten other patients with sleep-related periodic leg movements revealed abnormal responses in four. From these and other results, it is hypothesized that the sympathetic nervous system may mediate the periodicity of sleep related periodic leg movements.

Effects on sleep: a double-blind study comparing trimipramine to imipramine in depressed insomniac patients.

Trimipramine, a sedating tricyclic antidepressant, and imipramine were compared on polysomnographic parameters during a 4-week double-blind trial in depressed patients with insomnia and anxiety. Trimipramine eliminated objective evidence of sleep disturbance. This was not the case with imipramine, although depression improved similarly in both groups. Subjects' sleep appeared unchanged or more disturbed at the end of the treatment with imipramine. For trimipramine, the major changes in sleep parameters occurred during the first week of drug administration and did not parallel the gradual changes seen in the measures of depression. Additionally, trimipramine did not suppress REM sleep even in a subgroup of six trimipramine patients who had short rapid-eye-movement (REM) sleep latencies during the placebo baseline period, even though their depression was alleviated. The data demonstrate that (a) antidepressants may vary in their effects on sleep, even though they have similar effects on depression; (b) REM sleep suppression does not necessarily accompany improvement in depression; and (c) reports of improved sleep by patients undergoing antidepressant therapy may not reflect improvement on objective measures of sleep. The different sleep effects suggest the possibility of different antidepressant pathways.

Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults.

The effects of trazodone on sleep were compared with those of placebo and the sedating tricyclic antidepressant trimipramine in a double-blind crossover study in six healthy young men. Only trazodone significantly increased deep sleep without otherwise altering the normal architecture of sleep. The alpha-adrenergic receptor-blocking property of trazodone and a relative lack of noradrenergic reuptake blocking and the lack of anticholinergic effects are hypothesized to be responsible for the effects on sleep.

Gonadotropin secretion and hypothyroidism.

Hypothyroidism is generally associated with hypogonadotropism. Occasionally, however, increased gonadotropin concentrations are encountered. The mechanisms, presumably hypothalamic, which determine the gonadotropin shift are unclear. A case report of hyperprolactinemic hypothyroidism with associated hypergonadotropism is presented. The previous literature is reviewed. It appears that hypothyroidism is generally associated with a decrease in the gonadogropin secretion. However, hypothyroidism with exxagerated hTSH secretin and hyperprolactinemia can be associated with increased gonadotropin secretion.

[Various characteristics of industrial noise]. / Quelques caractéristiques du bruit industriel.

In this paper, broad characteristics of industrial noise are recalled briefly. High levels and multiple sources require special rules for the measurement or risk, such as the location of microphones at the height of the worker's ear. Industrial noise is either continuous-, and in such case one measurement is enough to evaluate the amount of risk for the inner ear-or fluctuates with time. This is the reason why noise level meters which integrate noise levels along time, must be used in many industrial situations and risk expressed in equivalent level. The unit for industrial noise is the dB(A) which is now universally admitted as reflecting satisfactorily the differential sensitivity of the ear. Lastly, the worker's exposure is also determined by the size (among other factors) of the workshop in which the noise source is located. Authors recommend that noise measurement in industry should not be limited to hygienic purposes and protection against industrial deafness but extended to other requirements of workers. In this respect, physical noise level measurement should be considered as one part of a noise abatement program and be completed by a survey on workers feeling of disturbance and uneasiness.

[Demonstration of a control lever for a simulator of visual aptitudes]. / Présentation d'un manche-réponse pour un simulateur d'aptitudes visuelles.

In this paper, the design and testing of the control of a new visual screener are described. The equipment is composed of a push-pull lever, an electronic digitalizer and a display on which Landolt rings are presented. The problem to be solved was to check whether the eight directions in which the lever could be oriented were equally reliable. For this purpose, 24 untrained subjects were required to respond to 108 by-chance oriented optotypes. This experiment demonstrated that the device was reliable in this respect that it produced very few errors; however, fiability was unequally distributed over the eight orientations. Suggestions for improvement were made.

Clinical assessment alone will not benefit patients with coronary heart disease: failure to achieve cholesterol targets in 12,045 patients--the Healthwise II study.

Healthwise II, a nurse-led audit programme in primary care during 1999-2002, assessed the uptake of secondary preventative measures for coronary heart disease (CHD). Risk factors, cardiovascular medications and blood cholesterol were recorded; 'at risk' patients were invited for a review after 6 months. Of 17,570 patients assessed, CHD was clinically present in 12,045 (69%); in these, aspirin usage was high (78%) but fewer patients were on a beta-blocker (40%), angiotensin-converting enzyme inhibitor (27%) or statin (49%). Blood pressure (BP) was controlled (<140/90) in only 41% of patients. Total cholesterol was >5 mmol/l in 49% of all CHD patients, half of whom were taking a statin. In the statin users, total cholesterol was uncontrolled (>5 mmol/l) in 38%. At follow-up, BP control remained at 42%, statin use increased to 57% and cholesterol remained elevated in 46%. Simple assessment in an audit programme fails to trigger change, and risk-factor modification for CHD remains inadequate.

The various strategies within the TyrR regulation of Escherichia coli to modulate gene expression.

The TyrR Regulon of Escherichia coli comprises eight transcription units whose expression is modulated by the TyrR protein. This protein, which is normally a homodimer in solution, can self-associate to form a hexamer, bind with high affinity to specific DNA sequences (TyrR boxes) and interact with the alpha subunit of the RNA polymerase. These various reactions are influenced by the abundance of one or more of the aromatic amino acids, tyrosine, phenylalanine or tryptophan and by the specific location and sequence of the TyrR boxes associated with each transcription unit. This review describes how these activities can be combined in different ways to produce a variety of responses to varying levels of the three aromatic amino acids.

Molecular analysis of the regulatory region of the Escherichia coli K-12 tyrB gene.

The tyrB gene from Escherichia coli K-12 was cloned and sequenced, and the transcriptional start point of tyrB was determined by primer extension. By using a fusion plasmid in which the lacZ structural gene is transcribed from the tyrB promoter, it was shown that the expression of tyrB is controlled at the transcriptional level by the TyrR protein, with tyrosine as corepressor. The fusion plasmid was used to isolate mutants in which the repression of tyrB had been abolished. The tyrB promoter-operator region of these mutants was sequenced, and the tyrB operator was identified. A comparison between the tyrB operator and those of the other genes belonging to the tyrR regulon is presented.

Autoregulation of the tyrR gene.

Strains of Escherichia coli K-12 in which the transcription of lacZ is initiated from the tyrR promoter have been constructed by use of the Mu d (Apr lac) phage of Casadaban and Cohen (Proc. Natl. Acad. Sci. U.S.A. 76:4530-4533, 1979). These strains have been used to examine the regulation of expression from the tyrR promoter, with the synthesis of beta-galactosidase used as an index of expression. The specific activity of beta-galactosidase fell to 51% upon introduction of lambda (Tn10) tyrR+; to 39% upon introduction of F123, an F-prime carrying tyrR+; to 29% upon introduction of pMU309, a derivative of the plasmid RP4 carrying tyrR+; and to 13.6% upon introduction of pMU352, a derivative of the multicopy plasmid pBR322 carrying tyrR+. These results indicate that the tyrR gene product interacts with its own promoter-operator region, decreasing synthesis of beta galactosidase in the tyrR::Mu d (Apr lac) strains. The increasing extent of repression of beta-galactosidase synthesis with increasing tyrR+ gene dosage was accompanied by increasing repression of the synthesis of tyrosine- and phenylalanine-repressible 3-deoxy-D-arabinoheptulosonic acid-7-phosphate synthetases. The interaction of the repressor with tyrRo appears unusual in the sense that aporepressor alone is probably one of the repressing species. The levels of beta-galactosidase synthesized in the tyrR::Mu d (Apr lac) strains indicate that tyrR has a relatively efficient promoter, the maximum levels representing on the order of a relatively efficient promoter, the maximum levels representing on the order of 1,000 monomers of beta-galactosidase per cell in the tyrR strain and about 500 monomers in the tyrR+ haploid strain.

Aromatic amino acid biosynthesis: regulation of shikimate kinase in Escherichia coli K-12.

Starvation of cells of Escherichia coli K-12 for the aromatic amino acids results in an increased rate of synthesis of shikimate kinase activity. The two controlling amino acids are tyrosine and tryptophan, and starvation for both results in derepression. The product of the regulator gene tyrR also participates in this control, and shikimate kinase synthesis was depressed in tyrR mutants. Chromatography of cell extracts on diethylaminoethyl-Sephadex allowed partial separation of two shikimate kinase enzymes and demonstrated that only one of these subject to specific repression control involving tyrR. By contrast, chromatography of cell extracts with G-75 or G-200 columns revealed a singl-molecular-weight species of shikimate kinase activity with an apparent molecular weight of 20,000. The levels of shikimate kinase in a series of partial diploid strains indicated that aroL, the structural gene for the tyrR-controlled shikimate kinase enzyme, is located on the E. coli chromosome between the structural genes proC and purE. By means of localized mutagenesis, an aroL mutant of E. coli was isolated. The mutant was an aromatic prototroph and, by the criterion of column chromatography, appeared to have only a single functional species of shikimate kinase enzyme.

Genetic analysis of mutant strains of Escherichia coli requiring p-aminobenzoic acid for growth.

Mutant strains of Escherichia coli K-12 which required p-aminobenzoic acid for growth were isolated. The mutations were mapped by conjugation and by transduction, and two genes concerned with the biosynthesis of p-aminobenzoic acid were identified.

Molecular cloning of pheR in Escherichia coli K-12.

The regulator gene pheR, which in Escherichia coli controls the expression of pheA, the structural gene for chorismate mutase P-prephenate dehydratase, was cloned on to multicopy plasmids directly from the E. coli chromosome; this was achieved with the aid of the tetracycline resistance transposon, Tn10, that had been inserted very close to the pheR gene. Subsequently, pheR was subcloned on a 1.1-kilobase-pair fragment on the plasmid vector pBR322; its position on the plasmid was localized by the method of gamma delta-mediated transpositional inactivation. The pheR gene product was identified in maxicells and found to be a protein of subunit molecular weight 19,000, suggesting that the coding segment of the gene is about 500 nucleotide pairs long.

Regulation of phenylalanine biosynthesis in Escherichia coli K-12: control of transcription of the pheA operon.

Bacteriophage lambda ppheA-lac was used to obtain strains of Escherichia coli K-12 in which pheA and lacZ are each transcribed from a separate pheA promoter. Mutants in which both beta-galactosidase and chorismate mutase P-prephenate dehydratase (the pheA gene product) were derepressed were isolated, and a transacting gene (pheR) was identified. pheR was mapped at min 93 on the E. coli chromosome; pheR mutants acquired the wild-type phenotype when either F117 (which covers the 93-min region) or F116 (which covers min 59 to 65) was introduced into the cell. A rifampin resistance mutation, rpoB366, was found to derepress transcription of the pheA operon. pheR and rpoB366 affected two different systems for the phenylalanine-mediated control of pheA. A mutation in miaA (trpX), a gene known to be involved in attenuation in the tryptophan operon, was also shown to increase transcription of the pheA gene.